Parkinson Disease
Conditions
Keywords
Parkinson's Disease, Motor symptoms, Tremor, tolerability, safety, cognition, anxiety, psychosis, mood, dyskinesia, sleep, cannabidiol, cannabis, efficacy, non-motor symptoms, quality of life, seborrhea
Brief summary
The major purpose of this study is to assess the efficacy of CBD on motor symptoms of Parkinson's Disease (PD), and secondarily to study the safety and tolerability of CBD and other efficacy, particularly regarding tremor in PD. The study has been powered to detect a clinically significant reduction in Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor scores. This is a 1:1 parallel, double-blind, randomized controlled trial (RCT) with 60 participants. The investigators will be recruiting up to 75 participants; the goal is to have 60 participants (30 in CBD group and 30 in placebo group) complete the study. The study drug is obtained from the National Institute on Drug Abuse (NIDA).
Detailed description
Persons with PD have progressive disabling tremor, slowness, stiffness, balance impairment, cognitive deficits, psychiatric symptoms, autonomic dysfunction, fatigue and insomnia. Tremor may interfere with necessary daily and work functions. The disorder affects approximately seven million people globally. The total economic cost in the US is around 23 billion dollars. In addition to economic costs, PD reduces quality of life of those affected and their caregivers. Cognitive impairment is a common feature and ranges from delayed recall in early stages to global dementia in up to 80% at end stage. PD with dementia has been associated with reduced quality of life, shortened survival, and increased caregiver distress. Community-based studies have estimated the point prevalence for dementia in PD to be 28% and 44%. Depression, anxiety and psychosis are also common and are particularly disabling in PD, even at the earliest stages. These symptoms have important consequences for quality of life and daily functioning, are associated with increased carer burden and risk for nursing home admission. Anxiety affects up to 40% of patients with PD, and may predate motor symptoms by several years. The most common anxiety disorders in PD are panic attacks (often during off-periods), generalized anxiety disorder, and simple and social phobias. Psychotic symptoms vary in frequency according to the definition used. If mild forms are included, these affect up to 50% of patients. Visual hallucinations are the most common type. However, hallucinations occur in all sensory domains and delusions of various types are also relatively common. The impact of psychosis is substantial in that it is associated with dementia, depression, earlier mortality, greater caregiver strain, and nursing home placement. Thus, it is crucial to treat these symptoms in order to optimize the management of PD patients. Generally, however, current therapies are inadequate. Medications have improved the prognosis of PD, but also have problematic adverse effects. Since treatment of PD is often unsatisfactory and since cannabis has recently become legal and readily available in Colorado, persons with PD have been trying it. Patients have heard from the internet, support groups and other sources that marijuana is helpful. Most are doing so on their own, without the supervision or even knowledge of their neurologist. In a survey conducted in the spring of 2014 in University of Colorado Hospital Movement Disorders clinic about 5% of 207 PD patients, average age 69, reported using cannabis. In another study reported that 25% of PD patients had taken cannabis in the General University Hospital in Prague. In the investigators clinics, about 30% of the PD patients have asked doctors during their clinic visits over the past 6 months about cannabis. In an anonymous web-based survey, 72% PD patients reported current or past using medical cannabis, and 48% reducing prescription medication since beginning cannabis use. PD mostly affects the elderly, and affected persons often have cognitive, psychiatric and motor problems, such as being prone to falling. Cannabis is well documented to cause psychosis, anxiety, slowness and incoordination. Studies have also shown that chronic users have structural and functional Central Nervous System (CNS) alterations. Thus cannabis is expected to be risky in persons with PD. Further, there are many components of cannabis, and the cannabis preparations being sold in Colorado vary widely in composition. There are no definitive data regarding the benefits and risks in of these various preparations in PD. Studies on safety and efficacy are greatly needed to protect this fragile Colorado population. Human trials report that CBD decreases anxiety and causes sedation in healthy individuals, decreases psychotic symptoms in schizophrenia and PD, and improves motor and non-motor symptoms and alleviates levodopa-induced dyskinesia in PD. Given the current literature regarding CBD: possible neuroprotective effect, good tolerability, anxiolytic and antipsychotic effects and general lack of information in PD, including its effect on tremor, the investigators feel that it is important to study its use in PD further. The investigators hypothesized that it would reduce tremor, anxiety and psychosis, and would be well tolerated in PD. The Specific Aims are: Primary Specific Aim: To evaluate the efficacy of CBD on motor symptoms in PD, specifically on the motor section of the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS). Secondary Specific Aim: To assess the safety and tolerability of CBD in PD, and to examine the effect of CBD on severity & duration of intractable tremor, night-time sleep, rigidity, emotional dyscontrol, anxiety and pain in PD. Exploratory Analyses: To study the efficacy of CBD on cognition, psychosis, sleep, daytime sleepiness, mood, fatigue, impulsivity, bladder function, other motor and non-motor PD signs, restless legs syndrome and Rapid Eye Movement (REM) sleep behavior disorder and quality of life. To explore the effect of CBD on plasma levels in PD. The study is a randomized, placebo controlled, double-blind parallel design with two treatment arms, each of approximately 2-3 weeks duration. In the 2-3 week treatment phase participants will start study drug and titrate up to the maximum tolerated or targeted dose (2.5 mg/kg/day of CBD). Each participant will have a screening visit, baseline visit within 3 weeks, 1 liver function monitoring visits on 3rd to 5th day of 2.5 mg/kg/day, 2 dose assessment visit (1.25 mg/kg/day and 2.5 mg/kg/day), and a safety visit (6 visits total). Participants will be evaluated on the 3rd to 5th day at each dose level for monitoring liver function and adverse events, as well as changes in medical history and concomitant medications. Participants are called 3 days and 1 week after stopping the study drug to check for signs of withdrawal.
Interventions
DRUGCannabidiol
Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution
OTHERPlacebo
Subjects randomized to this arm will receive Placebo
Sponsors
Colorado Department of Public Health and Environment
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants 40 - 85 years of age. * Willing and able to give informed consent (including through use of a legally authorized representative (LAR), if necessary). * Idiopathic PD, per UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria * ON motor MDS UPDRS \>20. * Anti-parkinsonian medication is fixed for at least one month prior to the day the participant starts study drug treatment. * If MoCA\<22 participant must have a designated caregiver that agrees to ensure study protocols followed. This includes accompanying patient to study visits and being available for study phone calls. * Must have a driver or available transportation (including provided Uber vouchers) to drive them to and from study visits and for other transportation needs during the treatment period. * Has a significant other (someone who knows the participant well) that is appropriate for doing the NPI assessment, and agrees to do so * Agrees to not take more than 1 gram per day of acetaminophen, due to a possible interaction with study drug that could increase risk of hepatotoxicity.
Exclusion criteria
* Known or suspected allergy to cannabinoids or excipients used in the study drug formulation. * Cannabis is detectable at the screening visit by blood testing or at the baseline visit by urine testing. If cannabis is detected at either the screening or baseline visit, then the participant is a screen fail and may return \>14 days later for a repeat screening visit. If cannabis is again detected at either the screening or baseline visit, then the participant is excluded and not allowed to rescreen. * History of drug or alcohol dependence; defined by prior inpatient stay(s) for this or that patient states s/he has a history of this. * Use of dopamine blockers within 180 days and amphetamine, cocaine, and MAO-A inhibitors within 90 days of baseline. * Currently taking tolcapone, valproic acid, felbamate, niacin (nicotinic acid) at ≥2000 mg/day or nicotinamide (nicotinic acid amide or nicotinamide) at ≥3000 mg/day, isoniazid and ketoconazole due to risk of liver injury and clobazam and ketoconazole because of risk of toxic interactions with the study drug. These medications need to be stopped 90 days before the baseline visit. * Unstable medical condition. * Any of the following laboratory test results at screening: Hemoglobin \< 10 g/dL WBC \<3.0 x 109/L Neutrophils \<1.5 x 109/L Lymphocytes \< 0.5 x 109/L Platelets \<100 x 109/L Hemoglobin A1C \> 9% * Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of normal. Persons with stable liver disease of known etiology can be included, unless total bilirubin or prothrombin time/INR is abnormal. * Is pregnant or lactating, or has a positive pregnancy test result pre-dose. * If a sexually active female, is not surgically sterile or at least two years post-menopausal, or does not agree to utilize an effective method of contraception from screening through at least four weeks after the completion of study treatment, using one of the following: barrier methods (diaphragm or partner using condoms plus use of spermicidal jelly or foam, preferably double-barrier methods); oral or implanted hormonal contraceptive; intrauterine device (IUD); or vasectomized male partner. * Planned elective surgery during study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) Scores | From baseline to the end of 2.5 mg/kg/day of CBD, through 3 weeks | Movement Disorders Society-Unified Parkinson's disease rating scale(MDS UPDRS) Part III assesses the motor signs of PD. There are 33 scores based on 18 items, several with right, left or other body distribution scores.Each question is anchored with five responses that are linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The possible change may be the scores of the total 33 scores. Scores ranges 0 -132. Higher values represent a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Liver Function Monitoring --Liver Function Test | Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks. | Liver function tests will be performed and evaluated at each clinic visit from baseline through 3 weeks. The result is reported as the number of participants that had a clinically significant change in the values of the liver function test, including aspartate aminotransferase (AST), Alanine transaminase (ALT), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (Alk Phos), Total Bilirubin (TB). |
| The Number of Participants Wtih Liver Function Impairment Related Adverse Events | Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks. | Liver function impairment will be evaluated and then related to adverse events and documented at each clinic visit. The change may be the frequency and severity of liver function impairment related AEs, including nausea/vomiting, diarrhea, abdominal pain, fatigue, weakness, chills, appetite changes, weight loss or gain, fever, etc. |
| Change in Blood Pressure (Systolic) | Baseline; at the end of 2.5 mg/kg/day, through 3 weeks | Standing systolic blood pressure measurements will be assessed through 3 weeks. The change may be the value of systolic blood pressure. |
| Change in Vital Signs-heart Rate | Baseline; at the end of 2.5 mg/kg/day, through 3 weeks | The change may be Heart rate (beat/minute) while standing. |
| Change in Vital Signs--weight | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be weight in kilograms or lbs. |
| Change in Vital Signs--temperature (Fahrenheit Degree) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be temperature in Fahrenheit degree |
| Change in Physical Exam | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The result is reported as the number of participants that had a clinically significant change in the physical exam findings, including allergic immunologic, cardiovascular, constitutional symptoms, ENT, endocrine, eyes, gastrointestinal, genitourinary, hematologic, integumentary, musculoskeletal, neurological, psychiatric, respiratory and other symptoms clinical significant findings. |
| Change in Neurological Exam | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The result is reported as the number of participants that had a clinically significant change in the general neurological exam clinical significant findings, including cranial nerves, motor strength, sensation, reflexes, gait, and other movements. |
| Change in Electrocardiograms | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The result is reported as the number of participants that had a clinically significant change in the EKG. |
| Change in Laboratory Values--hematology | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The result is reported as the number of participants that had a clinically significant change in the values of Hematology parameters, including RBC, WBC, HB, PLT, et al. |
| Change in Laboratory Values--chemistry | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The result is reported as the number of participants that had a clinically significant change in the values of the Chemistry profile, including BUN, CR, Electrolyte, glucose, liver function, etc. |
| Change in Montreal Cognitive Assessment (MoCA) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. The change may be the scores of MoCA, which is ranging from 0-30. Higher values represent a worse outcome. |
| Change in Wechsler Test for Adult Reading | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Wechsler test for Adult Reading. Wechsler Test of Adult Reading (WTAR) - Word reading tests are an established method of establishing a premorbid estimate of verbal intellectual functioning, which will serve as an estimate of premorbid cognitive reserve. The WTAR comprises 50 words with irregular pronunciations that participants read aloud. The raw score can be transformed to an age-adjusted standard score, which is used to predict IQ (M = 100; SD = 15). Scores higher means better. |
| Change in Grooved Pegboard Test | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change are the scores of Grooved Pegboard Test for the dominant affected hand. Manipulative dexterity, including finger speed, is assessed. Scoring is the time it took the participant to complete the task. Start the clock once the participant starts and stop it once the task has been completed. If after five minutes the participant has not completed the pegboard, stop the participant. The score the higher the worse. |
| Change in Symbol Digit Modalities Test | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Intellectual functioning estimate, Symbol digit modalities test (SDMT). The SDMT is a measure of processing speed and working memory that has proven to be sensitive to cognitive impairment in MS that has both oral and written trials (only the oral trial will be administered given the anticipated difficulty patients will have with tremor). Participants are presented with a key at the top of a page pairing unique symbols with single digits. Participants are required to provide the correct digit with symbols that are presented on the rest of the page. The score is the number of correctly coded items from 0-110. The number of correct responses provided in 90 seconds on the oral trial is recorded. Scores range 0-110 items. The higher the score the better. |
| Change in Paced Auditory Serial Addition Test | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Intellectual functioning estimate, Paced auditory serial addition test. Paced Auditory Serial Addition Test (PASAT) - The PASAT is a more complex measure of processing speed and working memory in which a series of digits is presented to participants at varying intervals (i.e., 2 seconds, 3 seconds). Participants must add each digit to the immediately preceding digit for the duration of each trial. The number of correct responses for each trial is recorded. The score for the PASAT is the total number correct out of 60 possible answers. The higher, the better. |
| Change in Controlled Oral Word Association Test | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Intellectual functioning estimate, Controlled oral word association test (COWAT). The COWAT is a measure of speeded verbal fluency and word retrieval in which participants are asked to say as many words as they can that begin with each of three letters for 60 seconds. The total number of words generated across all three trials is recorded. The higher, the better. |
| Change in Hopkins Verbal Learning Test-total Learning | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Intellectual functioning estimate, Hopkins verbal learning test-revised. Hopkins Verbal Learning Test-Revised (HVLT-R) - The HVLT-R is a measure of verbal learning and memory in which participants are asked to learn a 12-item word list over three trials (total immediate learning). When scoring, the three leaning trials are combined to calculate a total recall score. Score ranges 0-36. The higher, the better. The outcoe measure is reporting the change from baseline in the total leaning score across all three trials. |
| Change From Baseline for the Delayed Recall Trials Score of HVLT-R | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed recall trial. The participant is asked to recall as many words as they can 20-25 minutes after being presented the word list. The range is 0-12; the higher, the better. |
| Change From Baseline in Hopkins Verbal Learning Test-Delayed Recognition Trial | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Intellectual functioning estimate, Hopkins verbal learning test-revised. Hopkins Verbal Learning Test-Revised (HVLT-R) is a measure of verbal learning and memory in which participants are asked to learn a 12-item word list over three trials (total immediate learning). Delayed recognition trials is composed of 24 words, including the 12 target words and 12 false-positives, 6 semantically related, and 6 semantically unrelated. Retention % = percentage retained or delayed recall divided by better score on trial 2 or 3. Range 0-1. The higher, the better. |
| Change in Judgment of Line Orientation | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Intellectual functioning estimate, Judgment of line orientation. Judgment of Line Orientation (JOLO) - The JOLO is test of visuospatial functioning which measures a person's ability to match the angle and orientation of lines in space. Patients are asked to match two angled lines to a set of 11 lines that are arranged in a semicircle and separated 18 degrees from each other. Score ranges 0-30. The higher, the better. |
| Change in Semantic Verbal Fluency | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The change may be the scores of Semantic verbal fluency. Semantic Verbal Fluency - Semantic Verbal fluency is a measure of speeded verbal fluency and word retrieval in which participants are asked to say as many animal names/fruits and vegetables for 60 seconds. The total number of words generated across all three trials is recorded. The higher the score is, the better. |
| Change in Anxiety Short Form Response | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Comprised of 8 items which has five response options. Anxiety short form - is component of the Neurol-QOL (Quality of Life in Neurological Disorders) Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute. The change may be the total scores of the 8 items. Higher values represent a worse outcome. Scores range 8-40. |
| Change in Neuropsychiatric Inventory (NPI) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Valid and reliable scale to provide a means of assessing neuropsychiatric symptoms and psychopathology of patients. The change may be the scores of NPI. Neuropsychiatric Inventory (NPI) - is a valid and reliable scale. It was developed to provide a means of assessing neuropsychiatric symptoms and psychopathology of patients with Alzheimer's disease and other neurodegenerative disorders. It has proven to be sensitive to change and has been employed to capture treatment related behavioral. The NPI is administered to a caregiver/significant other who has detailed knowledge of the participant's behavior. Higher values represent a worse outcome. Score ranges 0-12. |
| Change in Scales of Outcomes in Parkinson's Disease (SCOPA) Sleep-daytime Sleepiness | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Scales for Outcomes in Parkinson's disease (SCOPA)sleep - is a valid, reliable, short scale for assessing daytime sleepiness (DS) and nighttime sleep problems (NS) in patients with PD. The DS sub scale evaluates daytime sleepiness and includes six items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-18. The higher the worse. The other |
| Change in Depression Short Form | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Comprised of 8 items which item has five response options. Depression short form - is a component of the Neurol-QOL (Quality of Life in Neurological Disorders) Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute. The change may be the scores of the total 8 items. Score ranges 0-40. Higher values represent a worse outcome. |
| Change in Emotional and Behavioral Dyscontrol Short Form | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Comprised of 8 items which item has 5 response options. Emotional and behavioral dyscontrol short form - is a component of the Neurol-QOL Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute. The change may be the total scores of the 8 items. Score ranges 0-40. Higher values represent a worse outcome. |
| Change in Stanford Sleepiness Scale | Pre- and 3 hours post- dose at baseline visit | Is a quick and easy way to assess how the participant is feeling. The change may be the scores of the scale 3 hours after dosing compared to pre-dosing. Stanford Sleepiness Scale (SSS): The Stanford Sleepiness Scale is a quick and easy way to assess how alert the participant is feeling. SSS is validated and probably the most widely used instrument for the assessment of participant's sleepiness. Score ranges 0-7. Higher values represent a worse outcome. |
| Change in Pain Intensity 3a Short Form | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Assess how much a person hurts. The change may be the score of the short form. Pain Intensity 3a short form - components of the Patient Reported Outcome Measurement Information System (PROMIS), which was developed by the NIH to provide a standardized metric for measuring physical, mental, and social health across chronic diseases. PROMIS instruments were developed using item response theory and have been tested in more than 20,000 individuals drawn from the general US population. The Pain Intensity instrument assesses how much a person hurts. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Each question has five response options ranging in value from one to five. Score ranges 0-15. Higher values represent a worse outcome. |
| Change in Pain Interference 4a Short Form | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Self-reported consequences of pain on relevant aspects of one's life. The change may be the scores of the short form. The Pain Interference instrument measures the self-reported consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Each question has five response options ranging in value from one to five. Score ranges 0-20. Higher values represent a worse outcome. |
| Change in Fatigue Severity Scale | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Self-report 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. The change may be the total scores of the 9 items, ranging from 9-63. Higher values represent worse outcome. |
| Change in Movement Disorder Society Unified Parkinson Disease Rating Scale | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Movement Disorder Society Unified Parkinson Disease Rating Scale. There are four parts, non-motor experiences of daily living, motor experiences of daily living, motor examination, and motor complications. The change may be the total scores of the four parts. Total score ranges 0-260. Higher values represent a worse outcome. |
| Change in Unified Dyskinesia Rating Scale | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | To evaluate involuntary movements often associated with treated PD. The change may be the total scores of the scale, including historical sub-score (0-60) and objective sub-score (0-44). The total score is historical sub score plus objective sub score, ranged from 0- 104. Higher values represent a worse outcome. |
| Change in the Timed UP&GO (TUG) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | The Timed Up & Go (TUG) test is a physical performance measure in which the ability to rise up from a seated chair position, walk 3m, turn, walk back, and sit down is timed. This measure is useful in an outpatient setting, because it requires only a few minutes, is easy to administer, and requires little equipment. Importantly, the TUG test is highly correlated with functional mobility, gait speed, and falls in older adults. The change may be the time duration (seconds) of performing the task. The higher, the worse. |
| Change in IRLS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | International restless legs syndrome (IRLS) study group rating scale for restless legs syndrome. The change may be the scores of the IRLS, ranged from 0-40. Higher values represent a worse outcome. |
| Change in Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | REM sleep behavior disorder screening questionnaire (RBDSQ). The change may be the total scores of RBDSQ. REM sleep behavior disorder screening questionnaire (RBDSQ) - is a 10-item, patient self-rating instrument assessing the participant's sleep behavior with short questions that have to be answered by either yes or no. Items 1 to 4 address the frequency and content of dreams and their relationship to nocturnal movements and behavior. Item 5 asks about self-injuries and injuries of the bed partner. Item 6 consists of four sub items assessing nocturnal motor behavior more specifically, e.g., questions about nocturnal vocalization, sudden limb movements, complex movements, or bedding items that fell down. Items 7 and 8 deal with nocturnal awakenings. Item 9 focuses on disturbed sleep in general and item 10 on the presence of any neurological disorder. The maximum total score of the RBDSQ is 13 points. Score ranges 0-13 points. Higher values represent a worse outcome. |
| Change in Overactive Bladder Symptom Score | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | A validated self-administered questionnaire consisting of 7 questions on a 5-point Likert scale. The change may be the scores of the scale, ranged from 0-35. Higher values represent a worse outcome. |
| Change in Parkinson's Disease Questionnaire (PDQ-39) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | A reliable valid responsive acceptable and feasible tool for assessment of quality of life in PD, including 39 multiple-choice items covering 8 dimensions: mobility (#1-10), activities of daily living (#11-16), emotional well-being (#17-22), stigma (#23-26), social support (#27-29), cognition (#30-33), communication (#34-36), and bodily discomfort (#37-39). 5-point ordinal scoring system: 0=never, 1= occasionally, 2=sometimes, 3=often, 4=always. The change may be the total scores of PDQ-39, ranged from 0-156. Higher values represent a worse outcome. |
| Change in EuroQol-5 Dimension-5 Level | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Consists of 2 pages-the EuroQol-5 Dimension-5 level (EQ-5D-5L) descriptive system and the EuroQol (EQ) Visual analogue scale. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS records the patient's self-rated health on a vertical visual analogue-scale, where the endpoints are labelled the best health you can imagine and the worst health you can imagine. The change may be the scales of EQ-5D. Score ranges 11111-55555. The higher, the worse. |
| Difference in Proportion of Participants That Discontinue the Study Due to Study Drug Intolerance | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Difference in Proportion of participants that discontinue the study due to study drug intolerance. The change may be the number of patients dropped out. |
| Change in Total Scores on Items 3.17 and 3.18 in MDS-UPDRS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Rest tremor amplitude and constancy of rest tremor scores in MDS UPDRS. The change may be the sum scores of 3.17 and 3.18. Score ranged from 0-24. Higher values represent a worse outcome. |
| Change in Item 2.10 in MDS UPDRS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Patient's tremor experience. The change may be the scores of item 2.10. Score ranged from 0-4. Higher values represent a worse outcome. |
| Change in Item 3.15 and 3.16 in MDS UPDRS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Postural tremor of the hands and kinetic tremor of the hand. The change may be the sum scores of item 3.15 and 3.16. Score ranged from 0-16. Higher values represent a worse outcome. |
| Change in Rigidity Sub Scores in MDS UPDRS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Rigidity sub scores in MDS UPDRS. The change may be the sub scores of rigidity related item in MDS UPDRS (item 3.3). Score ranged from 0-20. Higher values represent a worse outcome. |
| Change in Bradykinesia Sub Scores in MDS UPDRS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Bradykinesia sub scores in MDS UPDRS. The change may be the sub scores of bradykinesia related items in MDS UPDRS, including items 3.4-3.8, and 3.14. The scores ranged from 0-44. Higher values represent a worse outcome. |
| Change in Axial Sub Scores in MDS UPDRS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Axial sub scores in MDS UPDRS. The change may be the sub scores of axial related items in MDS UPDRS, including items 3.9, 3.13, 3.10, 3.11, and 3.12. The sub scores ranged from 0-20. Higher values represent a worse outcome. |
| Change in Bulbar Sub Scores in MDS UPDRS | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Bulbar sub scores in MDS UPDRS (item 3.1 and 3.2). The change may be the sub scores of bulbar related items in MDS UPDRS, ranged from 0-8. Higher values represent a worse outcome. |
| Change in Insomnia Severity Index | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Insomnia Severity Index (ISI): ISI is a verified seven-item self-report questionnaire assessing the nature, severity, and impact of insomnia. A five-point Likert scale is used to rate each item (e.g., 0=no problem; 4=very severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28). A total score ranging from 0 to 28. Higher values represent a worse outcome. |
| Change in Pittsburgh Sleep Quality Index | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | To measure the quality and patterns of sleep in adults. It differentiates poor from good sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. The change may be the total scores, ranged from 0 to 42. The higher values represent a worse outcome. |
| Change in The Columbia-Suicide Severity Rating Scale (C-SSRS) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | C-SSRS is a suicidal ideation rating scale. The change may be the answers to the questions of C-SSRS. There are five questions and have binary responses (yes/no). Assign a score of 1 if answer yes and score of 0 if no . Higher values represent a worse outcome.The mximum score is 5. |
| Change in Dermatology Quality of Life Index | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Dermatology quality of life index. The change may be the scores of the questionnaire. The scoring of each question is as follows: very much=3, a lot =2, a little=1, not at all=0, not relevant =0. Question 7, prevented work or studying =3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. |
| Change in the Number of Participants With Presence of Seborrheic Dermatitis From Baseline to Final Visit. | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Dermatology photography evaluation. The change in number of participants with a presence of seborrheic dermatitis from baseline to final visit. Dermatology photography: take a picture of the central face, as this is the most common area of seborrhea, and send it, with appropriate privacy safeguards, to dermatologists, Dr. Robert Dellavalle, MD., and Dr. Andrea Steel. |
| The Number of Participants Wtih Treatment-related Adverse Events | Every 3-5 days at each dose level, assessed up to 3 weeks | Adverse events (AEs) are collected at each dose level. AEs collection include Serious Adverse Events (SAE), withdrawal symptoms and common AEs. SAE is an undesirable medical occurrence that results in death, or life-threatening, or inpatient hospitalization or prolongation of existing hospitalization or significant disability or incapacity or in a congenital anomaly/birth defect. Withdrawal and common AEs include headache, anxiety, nausea/vomiting, tremor, chills, decreased concentration, increased concentration, agitation, irritability, sleep disturbances, mood changes, somnolence, fatigue, anorexia, appetite changes, weight loss or gain, diarrhea, convulsion, abdominal pain, weakness, fever and other unexpected AEs. All of the these AEs will be recorded and counted. |
| Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Daytime Sleep (DS) Problems. | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Scales for Outcomes in Parkinson's disease (SCOPA) sleep DS subscale is a valid, reliable, short scale for assessing daytime sleep problems (DS) in patients with PD. The sub scale includes six items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-18. The higher the worse. |
| Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Nighttime Sleep (NS) Problems. | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Scales for Outcomes in Parkinson's disease (SCOPA) sleep NS subscale - is a valid, reliable, short scale for assessing nighttime sleep problems (NS) in patients with PD. The NS sub scale includes five items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-15. The higher the worse. |
| Change in Modified Dysfunctional Beliefs and Attitudes About Sleep Questionnaire (DBAS-16) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Modified Dysfunctional Beliefs and Attitudes about Sleep Questionnaire (DBAS-16): A validated self-reported questionnaire designed to identify and assess various sleep/insomnia-related cognitions (e.g., beliefs, attitudes, expectations, appraisals, attributions). range is 0-160; the higher numbers are worse. |
| Change in Wake After Sleep Onset | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | WASO, the total number of minutes that a person is awake after having initially fallen asleep; higher numbers are worse. |
| Difference of Plasma Interleukin 6 Level Between PD and Healthy Control Population | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Interleukin 6 is an inflammatory cytokine, and is measured in the blood. Whole bold was collected into tubes containing anticoagulant; tubes were inverted gently 3-4 times. Blood was allowed to clot at room temperature for 30 to 45 min, centrifuged at 1,000 x g for 15 min at 4°C and serum was transferred to a clean polypropylene tube. To completely remove platelets and precipitates, the tubes were centrifuge again at 10,000 x g for 10 min at 4°C. Processed samples were stored at -80°F, and cytokine levels measured using the Bio-Plex ProTM Human Cytokine Assay. |
| Change in Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS) - Total Scores | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | To measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. The result is the difference of the change of the total scores of QUIP-RS (excessive hobbies-punding and dopamine dysregulation syndrome) between groups. The total QUIP-RS scores is 0-112. Higher values represent a worse outcome. |
| Change in Non-motor Symptoms Scale for Parkinson's Disease (NMSS) | From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks | Validated 30-item scale for the assessment of NMS in PD. Each symptom scored with respect to severity (0=none, 1=mild, 2=moderate, 3=severe), frequency (1=rarely, 2=often, 3=frequent, 4=very frequent). Each NMSS item score is calculated by multiplying the severity and frequency score. The final score is the sum of the total 30-item scores. The change may be the total scores of NMSS, ranged from 0 to 360. The higher values represent a worse outcome. |
Countries
United States
Participant flow
Pre-assignment details
Between 9/5/2018 and 1/4/2022, 74 participants were screened, 61 randomized and 31 assigned to the CBD/THC drug and 30 to placebo. 13 participants were excluded: 8 participants not meeting inclusion criteria, and 5 declined to participate after screening.
Participants by arm
| Arm | Count |
|---|---|
| CBD Cannabis Extract Oral Solution Cannabidiol (CBD) Cannabis extract oral solution
Cannabidiol: Subjects randomized to this arm will receive Cannabidiol Cannabis extract oral solution | 31 |
| Placebo Placebo oral solution
Placebo: Subjects randomized to this arm will receive Placebo | 30 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | CBD Cannabis Extract Oral Solution | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 70.4 years STANDARD_DEVIATION 6.2 | 68.6 years STANDARD_DEVIATION 7.6 | 69.5 years STANDARD_DEVIATION 6.9 |
| Baseline • Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III | 34.6 units on a scale STANDARD_DEVIATION 9.1 | 30.9 units on a scale STANDARD_DEVIATION 9 | 32.8 units on a scale STANDARD_DEVIATION 9.3 |
| Baseline total Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) | 56.7 units on a scale STANDARD_DEVIATION 17.9 | 48.8 units on a scale STANDARD_DEVIATION 15.5 | 52.8 units on a scale STANDARD_DEVIATION 17.4 |
| Body weight | 79.0 kg STANDARD_DEVIATION 16.2 | 82.1 kg STANDARD_DEVIATION 12.4 | 80.5 kg STANDARD_DEVIATION 14.4 |
| Disease duration | 7.0 years STANDARD_DEVIATION 6.8 | 4.5 years STANDARD_DEVIATION 3.9 | 5.8 years STANDARD_DEVIATION 5.7 |
| Education, >=college educated | 23 Participants | 27 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 29 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Income >$75,000 | 17 Participants | 18 Participants | 35 Participants |
| Levodopa-equivalent daily dosage | 417.9 mg/day STANDARD_DEVIATION 440.3 | 427.5 mg/day STANDARD_DEVIATION 292.8 | 422.7 mg/day STANDARD_DEVIATION 370.7 |
| Married | 25 Participants | 23 Participants | 48 Participants |
| Modified Hoehn & Yahr | 2.47 units on a scale STANDARD_DEVIATION 0.69 | 2.30 units on a scale STANDARD_DEVIATION 0.48 | 2.39 units on a scale STANDARD_DEVIATION 0.61 |
| Montreal Cognitive Assessment (MoCA) | 26.9 units on a scale STANDARD_DEVIATION 3.6 | 27.1 units on a scale STANDARD_DEVIATION 2.2 | 27.0 units on a scale STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 28 Participants | 59 Participants |
| Region of Enrollment United States | 31 participants | 30 participants | 61 participants |
| Retired | 25 Participants | 24 Participants | 49 Participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Male | 18 Participants | 23 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 |
| other Total, other adverse events | 26 / 31 | 25 / 30 |
| serious Total, serious adverse events | 1 / 31 | 0 / 30 |
Outcome results
Primary
Change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) Scores
Movement Disorders Society-Unified Parkinson's disease rating scale(MDS UPDRS) Part III assesses the motor signs of PD. There are 33 scores based on 18 items, several with right, left or other body distribution scores.Each question is anchored with five responses that are linked to commonly accepted clinical terms: 0=normal, 1=slight, 2=mild, 3=moderate, and 4=severe. The possible change may be the scores of the total 33 scores. Scores ranges 0 -132. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day of CBD, through 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) Scores | -4.5714 units on a scale |
| Placebo | Change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) Scores | -2.7665 units on a scale |
p-value: 0.378595% CI: [-5.8839, 2.2741]Mixed Models Analysis
Secondary
Change From Baseline for the Delayed Recall Trials Score of HVLT-R
Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed recall trial. The participant is asked to recall as many words as they can 20-25 minutes after being presented the word list. The range is 0-12; the higher, the better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBD Cannabis Extract Oral Solution | Change From Baseline for the Delayed Recall Trials Score of HVLT-R | -1.16 change in units on a scale | Standard Error 0.6 |
| Placebo | Change From Baseline for the Delayed Recall Trials Score of HVLT-R | -0.28 change in units on a scale | Standard Error 0.26 |
Secondary
Change From Baseline in Hopkins Verbal Learning Test-Delayed Recognition Trial
The change may be the scores of Intellectual functioning estimate, Hopkins verbal learning test-revised. Hopkins Verbal Learning Test-Revised (HVLT-R) is a measure of verbal learning and memory in which participants are asked to learn a 12-item word list over three trials (total immediate learning). Delayed recognition trials is composed of 24 words, including the 12 target words and 12 false-positives, 6 semantically related, and 6 semantically unrelated. Retention % = percentage retained or delayed recall divided by better score on trial 2 or 3. Range 0-1. The higher, the better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBD Cannabis Extract Oral Solution | Change From Baseline in Hopkins Verbal Learning Test-Delayed Recognition Trial | 0.54 units on a scale | Standard Error 0.48 |
| Placebo | Change From Baseline in Hopkins Verbal Learning Test-Delayed Recognition Trial | 0.55 units on a scale | Standard Error 0.27 |
Secondary
Change in Anxiety Short Form Response
Comprised of 8 items which has five response options. Anxiety short form - is component of the Neurol-QOL (Quality of Life in Neurological Disorders) Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute. The change may be the total scores of the 8 items. Higher values represent a worse outcome. Scores range 8-40.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Anxiety Short Form Response | -2.1001 change in units on a scale |
| Placebo | Change in Anxiety Short Form Response | -3.4533 change in units on a scale |
p-value: 0.181995% CI: [-0.6511, 3.3576]Mixed Models Analysis
Secondary
Change in Axial Sub Scores in MDS UPDRS
Axial sub scores in MDS UPDRS. The change may be the sub scores of axial related items in MDS UPDRS, including items 3.9, 3.13, 3.10, 3.11, and 3.12. The sub scores ranged from 0-20. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Axial Sub Scores in MDS UPDRS | -0.2919 change in units on a scale |
| Placebo | Change in Axial Sub Scores in MDS UPDRS | -0.2667 change in units on a scale |
p-value: 0.946395% CI: [-0.7717, 0.7212]Mixed Models Analysis
Secondary
Change in Blood Pressure (Systolic)
Standing systolic blood pressure measurements will be assessed through 3 weeks. The change may be the value of systolic blood pressure.
Time frame: Baseline; at the end of 2.5 mg/kg/day, through 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Blood Pressure (Systolic) | -5.4145 change in mmHg |
| Placebo | Change in Blood Pressure (Systolic) | -0.9891 change in mmHg |
p-value: 0.271295% CI: [-12.4018, 3.551]Mixed Models Analysis
Secondary
Change in Bradykinesia Sub Scores in MDS UPDRS
Bradykinesia sub scores in MDS UPDRS. The change may be the sub scores of bradykinesia related items in MDS UPDRS, including items 3.4-3.8, and 3.14. The scores ranged from 0-44. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Bradykinesia Sub Scores in MDS UPDRS | -1.6787 change in units on a scale |
| Placebo | Change in Bradykinesia Sub Scores in MDS UPDRS | -0.8666 change in units on a scale |
p-value: 0.528595% CI: [-3.3743, 1.7501]Mixed Models Analysis
Secondary
Change in Bulbar Sub Scores in MDS UPDRS
Bulbar sub scores in MDS UPDRS (item 3.1 and 3.2). The change may be the sub scores of bulbar related items in MDS UPDRS, ranged from 0-8. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Bulbar Sub Scores in MDS UPDRS | -0.3376 change in units on a scale |
| Placebo | Change in Bulbar Sub Scores in MDS UPDRS | -0.03333 change in units on a scale |
p-value: 0.436295% CI: [-1.0817, 0.4732]Mixed Models Analysis
Secondary
Change in Controlled Oral Word Association Test
The change may be the scores of Intellectual functioning estimate, Controlled oral word association test (COWAT). The COWAT is a measure of speeded verbal fluency and word retrieval in which participants are asked to say as many words as they can that begin with each of three letters for 60 seconds. The total number of words generated across all three trials is recorded. The higher, the better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 29 participants performed the cognitive test from CBD group, and 29 from placebo group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Controlled Oral Word Association Test | 3.1675 change in units on a scale |
| Placebo | Change in Controlled Oral Word Association Test | 2.5916 change in units on a scale |
p-value: 0.770395% CI: [-3.3697, 4.5216]Mixed Models Analysis
Secondary
Change in Depression Short Form
Comprised of 8 items which item has five response options. Depression short form - is a component of the Neurol-QOL (Quality of Life in Neurological Disorders) Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute. The change may be the scores of the total 8 items. Score ranges 0-40. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Depression Short Form | -1.7300 change in units on a scale |
| Placebo | Change in Depression Short Form | -2.0367 change in units on a scale |
p-value: 0.837895% CI: [-2.6765, 3.2899]Mixed Models Analysis
Secondary
Change in Dermatology Quality of Life Index
Dermatology quality of life index. The change may be the scores of the questionnaire. The scoring of each question is as follows: very much=3, a lot =2, a little=1, not at all=0, not relevant =0. Question 7, prevented work or studying =3. The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Dermatology Quality of Life Index | -0.1763 change in units on a scale |
| Placebo | Change in Dermatology Quality of Life Index | 0.1000 change in units on a scale |
Secondary
Change in Electrocardiograms
The result is reported as the number of participants that had a clinically significant change in the EKG.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Electrocardiograms | 0 Participants |
| Placebo | Change in Electrocardiograms | 0 Participants |
Secondary
Change in Emotional and Behavioral Dyscontrol Short Form
Comprised of 8 items which item has 5 response options. Emotional and behavioral dyscontrol short form - is a component of the Neurol-QOL Measurement System, which is a collaborative effort of the National Institute of Neurological Disorders and Stroke and a number of partnering institutions. This measurement system was designed to be responsive to the needs of researchers in a variety of neurological disorders and to facilitate comparisons of data across clinical trials in different diseases. The short form is comprised of eight items that were selected from the respective item bank. Items have five response options (e.g., 1=Never, 2=Rarely, 3=Sometimes, 4=Often, 5=Always). Respondents generally can answer five questions per minute. The change may be the total scores of the 8 items. Score ranges 0-40. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Emotional and Behavioral Dyscontrol Short Form | -3.9870 change in units on a scale |
| Placebo | Change in Emotional and Behavioral Dyscontrol Short Form | -4.2733 change in units on a scale |
Secondary
Change in EuroQol-5 Dimension-5 Level
Consists of 2 pages-the EuroQol-5 Dimension-5 level (EQ-5D-5L) descriptive system and the EuroQol (EQ) Visual analogue scale. The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The VAS records the patient's self-rated health on a vertical visual analogue-scale, where the endpoints are labelled the best health you can imagine and the worst health you can imagine. The change may be the scales of EQ-5D. Score ranges 11111-55555. The higher, the worse.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in EuroQol-5 Dimension-5 Level | 0.05364 change in units on a scale |
| Placebo | Change in EuroQol-5 Dimension-5 Level | 0.02467 change in units on a scale |
p-value: 0.317895% CI: [-0.02857, 0.08651]Mixed Models Analysis
Secondary
Change in Fatigue Severity Scale
Self-report 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity. The change may be the total scores of the 9 items, ranging from 9-63. Higher values represent worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Fatigue Severity Scale | 1.4224 change in units on a scale |
| Placebo | Change in Fatigue Severity Scale | -1.3667 change in units on a scale |
p-value: 0.233995% CI: [-1.8523, 7.4304]Mixed Models Analysis
Secondary
Change in Grooved Pegboard Test
The change are the scores of Grooved Pegboard Test for the dominant affected hand. Manipulative dexterity, including finger speed, is assessed. Scoring is the time it took the participant to complete the task. Start the clock once the participant starts and stop it once the task has been completed. If after five minutes the participant has not completed the pegboard, stop the participant. The score the higher the worse.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 15 participants performed the cognitive test from CBD group, and 14 from placebo group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Grooved Pegboard Test | 5.3406 change in seconds |
| Placebo | Change in Grooved Pegboard Test | -14.3454 change in seconds |
p-value: 0.066195% CI: [-1.3733, 40.7452]Mixed Models Analysis
Secondary
Change in Hopkins Verbal Learning Test-total Learning
The change may be the scores of Intellectual functioning estimate, Hopkins verbal learning test-revised. Hopkins Verbal Learning Test-Revised (HVLT-R) - The HVLT-R is a measure of verbal learning and memory in which participants are asked to learn a 12-item word list over three trials (total immediate learning). When scoring, the three leaning trials are combined to calculate a total recall score. Score ranges 0-36. The higher, the better. The outcoe measure is reporting the change from baseline in the total leaning score across all three trials.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Hopkins Verbal Learning Test-total Learning | -2.03 change in units on a scale | Standard Error 1.06 |
| Placebo | Change in Hopkins Verbal Learning Test-total Learning | -1.30 change in units on a scale | Standard Error 1.15 |
p-value: 0.187495% CI: [-2.2172, 0.4504]Mixed Models Analysis
Secondary
Change in Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS) - Total Scores
To measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in PD. The result is the difference of the change of the total scores of QUIP-RS (excessive hobbies-punding and dopamine dysregulation syndrome) between groups. The total QUIP-RS scores is 0-112. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS) - Total Scores | -0.24 score on a scale |
| Placebo | Change in Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS) - Total Scores | 0.43 score on a scale |
Secondary
Change in Insomnia Severity Index
Insomnia Severity Index (ISI): ISI is a verified seven-item self-report questionnaire assessing the nature, severity, and impact of insomnia. A five-point Likert scale is used to rate each item (e.g., 0=no problem; 4=very severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28). A total score ranging from 0 to 28. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Insomnia Severity Index | -1.6982 change in units on a scale |
| Placebo | Change in Insomnia Severity Index | -1.6333 change in units on a scale |
p-value: 0.932795% CI: [-1.5957, 1.4659]Mixed Models Analysis
Secondary
Change in IRLS
International restless legs syndrome (IRLS) study group rating scale for restless legs syndrome. The change may be the scores of the IRLS, ranged from 0-40. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in IRLS | -1.2366 change in units on a scale |
| Placebo | Change in IRLS | -0.5667 change in units on a scale |
p-value: 0.616495% CI: [-3.3316, 1.9918]Mixed Models Analysis
Secondary
Change in Item 2.10 in MDS UPDRS
Patient's tremor experience. The change may be the scores of item 2.10. Score ranged from 0-4. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Item 2.10 in MDS UPDRS | -0.2280 change in units on a scale |
| Placebo | Change in Item 2.10 in MDS UPDRS | -0.100 change in units on a scale |
Secondary
Change in Item 3.15 and 3.16 in MDS UPDRS
Postural tremor of the hands and kinetic tremor of the hand. The change may be the sum scores of item 3.15 and 3.16. Score ranged from 0-16. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Item 3.15 and 3.16 in MDS UPDRS | -0.4291 change in units on a scale |
| Placebo | Change in Item 3.15 and 3.16 in MDS UPDRS | -0.6667 change in units on a scale |
Secondary
Change in Judgment of Line Orientation
The change may be the scores of Intellectual functioning estimate, Judgment of line orientation. Judgment of Line Orientation (JOLO) - The JOLO is test of visuospatial functioning which measures a person's ability to match the angle and orientation of lines in space. Patients are asked to match two angled lines to a set of 11 lines that are arranged in a semicircle and separated 18 degrees from each other. Score ranges 0-30. The higher, the better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 26 participants performed the cognitive test from CBD group, and 25 from placebo group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Judgment of Line Orientation | 0.1367 change in units on a scale |
| Placebo | Change in Judgment of Line Orientation | -1.1626 change in units on a scale |
p-value: 0.164695% CI: [-0.5533, 3.1519]Mixed Models Analysis
Secondary
Change in Laboratory Values--chemistry
The result is reported as the number of participants that had a clinically significant change in the values of the Chemistry profile, including BUN, CR, Electrolyte, glucose, liver function, etc.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Laboratory Values--chemistry | 0 Participants |
| Placebo | Change in Laboratory Values--chemistry | 0 Participants |
Secondary
Change in Laboratory Values--hematology
The result is reported as the number of participants that had a clinically significant change in the values of Hematology parameters, including RBC, WBC, HB, PLT, et al.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Laboratory Values--hematology | 0 Participants |
| Placebo | Change in Laboratory Values--hematology | 0 Participants |
Secondary
Change in Liver Function Monitoring --Liver Function Test
Liver function tests will be performed and evaluated at each clinic visit from baseline through 3 weeks. The result is reported as the number of participants that had a clinically significant change in the values of the liver function test, including aspartate aminotransferase (AST), Alanine transaminase (ALT), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (Alk Phos), Total Bilirubin (TB).
Time frame: Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Liver Function Monitoring --Liver Function Test | 0 Participants |
| Placebo | Change in Liver Function Monitoring --Liver Function Test | 0 Participants |
Secondary
Change in Modified Dysfunctional Beliefs and Attitudes About Sleep Questionnaire (DBAS-16)
Modified Dysfunctional Beliefs and Attitudes about Sleep Questionnaire (DBAS-16): A validated self-reported questionnaire designed to identify and assess various sleep/insomnia-related cognitions (e.g., beliefs, attitudes, expectations, appraisals, attributions). range is 0-160; the higher numbers are worse.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Modified Dysfunctional Beliefs and Attitudes About Sleep Questionnaire (DBAS-16) | -2.70 units on a scale | Standard Error 3.4 |
| Placebo | Change in Modified Dysfunctional Beliefs and Attitudes About Sleep Questionnaire (DBAS-16) | -4.57 units on a scale | Standard Error 3.3 |
Secondary
Change in Montreal Cognitive Assessment (MoCA)
Montreal Cognitive Assessment (MoCA) is a rapid screening instrument for mild cognitive dysfunction. The change may be the scores of MoCA, which is ranging from 0-30. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Montreal Cognitive Assessment (MoCA) | -0.8341 change in units on a scale |
| Placebo | Change in Montreal Cognitive Assessment (MoCA) | -0.5000 change in units on a scale |
p-value: 0.592195% CI: [-1.5749, 0.9068]Mixed Models Analysis
Secondary
Change in Movement Disorder Society Unified Parkinson Disease Rating Scale
Movement Disorder Society Unified Parkinson Disease Rating Scale. There are four parts, non-motor experiences of daily living, motor experiences of daily living, motor examination, and motor complications. The change may be the total scores of the four parts. Total score ranges 0-260. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Movement Disorder Society Unified Parkinson Disease Rating Scale | -6.2798 change in units on a scale |
| Placebo | Change in Movement Disorder Society Unified Parkinson Disease Rating Scale | -7.2333 change in units on a scale |
p-value: 0.755795% CI: [-5.1655, 7.0727]Mixed Models Analysis
Secondary
Change in Neurological Exam
The result is reported as the number of participants that had a clinically significant change in the general neurological exam clinical significant findings, including cranial nerves, motor strength, sensation, reflexes, gait, and other movements.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Neurological Exam | 0 Participants |
| Placebo | Change in Neurological Exam | 0 Participants |
Secondary
Change in Neuropsychiatric Inventory (NPI)
Valid and reliable scale to provide a means of assessing neuropsychiatric symptoms and psychopathology of patients. The change may be the scores of NPI. Neuropsychiatric Inventory (NPI) - is a valid and reliable scale. It was developed to provide a means of assessing neuropsychiatric symptoms and psychopathology of patients with Alzheimer's disease and other neurodegenerative disorders. It has proven to be sensitive to change and has been employed to capture treatment related behavioral. The NPI is administered to a caregiver/significant other who has detailed knowledge of the participant's behavior. Higher values represent a worse outcome. Score ranges 0-12.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Neuropsychiatric Inventory (NPI) | -0.3000 change in units on a scale |
| Placebo | Change in Neuropsychiatric Inventory (NPI) | -1.2667 change in units on a scale |
p-value: 0.228295% CI: [-0.6287, 2.5621]Mixed Models Analysis
Secondary
Change in Non-motor Symptoms Scale for Parkinson's Disease (NMSS)
Validated 30-item scale for the assessment of NMS in PD. Each symptom scored with respect to severity (0=none, 1=mild, 2=moderate, 3=severe), frequency (1=rarely, 2=often, 3=frequent, 4=very frequent). Each NMSS item score is calculated by multiplying the severity and frequency score. The final score is the sum of the total 30-item scores. The change may be the total scores of NMSS, ranged from 0 to 360. The higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Non-motor Symptoms Scale for Parkinson's Disease (NMSS) | -5.8652 change in units on a scale |
| Placebo | Change in Non-motor Symptoms Scale for Parkinson's Disease (NMSS) | -5.0333 change in units on a scale |
p-value: 0.808595% CI: [-7.6835, 6.0197]Mixed Models Analysis
Secondary
Change in Overactive Bladder Symptom Score
A validated self-administered questionnaire consisting of 7 questions on a 5-point Likert scale. The change may be the scores of the scale, ranged from 0-35. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Overactive Bladder Symptom Score | -0.09605 change in units on a scale |
| Placebo | Change in Overactive Bladder Symptom Score | 0 change in units on a scale |
p-value: 0.901695% CI: [-1.6449, 1.4528]Mixed Models Analysis
Secondary
Change in Paced Auditory Serial Addition Test
The change may be the scores of Intellectual functioning estimate, Paced auditory serial addition test. Paced Auditory Serial Addition Test (PASAT) - The PASAT is a more complex measure of processing speed and working memory in which a series of digits is presented to participants at varying intervals (i.e., 2 seconds, 3 seconds). Participants must add each digit to the immediately preceding digit for the duration of each trial. The number of correct responses for each trial is recorded. The score for the PASAT is the total number correct out of 60 possible answers. The higher, the better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 27 participants performed the cognitive test from CBD group, and 25 from placebo group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Paced Auditory Serial Addition Test | 6.9653 change in units on a scale |
| Placebo | Change in Paced Auditory Serial Addition Test | 11.9489 change in units on a scale |
p-value: 0.282795% CI: [-14.2093, 4.2421]Mixed Models Analysis
Secondary
Change in Pain Intensity 3a Short Form
Assess how much a person hurts. The change may be the score of the short form. Pain Intensity 3a short form - components of the Patient Reported Outcome Measurement Information System (PROMIS), which was developed by the NIH to provide a standardized metric for measuring physical, mental, and social health across chronic diseases. PROMIS instruments were developed using item response theory and have been tested in more than 20,000 individuals drawn from the general US population. The Pain Intensity instrument assesses how much a person hurts. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Each question has five response options ranging in value from one to five. Score ranges 0-15. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Pain Intensity 3a Short Form | -3.1209 change in units on a scale |
| Placebo | Change in Pain Intensity 3a Short Form | -2.6169 change in units on a scale |
p-value: 0.719795% CI: [-3.3015, 2.2934]Mixed Models Analysis
Secondary
Change in Pain Interference 4a Short Form
Self-reported consequences of pain on relevant aspects of one's life. The change may be the scores of the short form. The Pain Interference instrument measures the self-reported consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Each question has five response options ranging in value from one to five. Score ranges 0-20. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Pain Interference 4a Short Form | -0.1543 change in units on a scale |
| Placebo | Change in Pain Interference 4a Short Form | -2.7701 change in units on a scale |
p-value: 0.068695% CI: [-0.2058, 5.4373]Mixed Models Analysis
Secondary
Change in Parkinson's Disease Questionnaire (PDQ-39)
A reliable valid responsive acceptable and feasible tool for assessment of quality of life in PD, including 39 multiple-choice items covering 8 dimensions: mobility (#1-10), activities of daily living (#11-16), emotional well-being (#17-22), stigma (#23-26), social support (#27-29), cognition (#30-33), communication (#34-36), and bodily discomfort (#37-39). 5-point ordinal scoring system: 0=never, 1= occasionally, 2=sometimes, 3=often, 4=always. The change may be the total scores of PDQ-39, ranged from 0-156. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Parkinson's Disease Questionnaire (PDQ-39) | -4.8005 change in units on a scale |
| Placebo | Change in Parkinson's Disease Questionnaire (PDQ-39) | -4.4788 change in units on a scale |
p-value: 0.921995% CI: [-6.8584, 6.2151]Mixed Models Analysis
Secondary
Change in Physical Exam
The result is reported as the number of participants that had a clinically significant change in the physical exam findings, including allergic immunologic, cardiovascular, constitutional symptoms, ENT, endocrine, eyes, gastrointestinal, genitourinary, hematologic, integumentary, musculoskeletal, neurological, psychiatric, respiratory and other symptoms clinical significant findings.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Physical Exam | 0 Participants |
| Placebo | Change in Physical Exam | 0 Participants |
Secondary
Change in Pittsburgh Sleep Quality Index
To measure the quality and patterns of sleep in adults. It differentiates poor from good sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. The change may be the total scores, ranged from 0 to 42. The higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Pittsburgh Sleep Quality Index | -0.8226 change in units on a scale |
| Placebo | Change in Pittsburgh Sleep Quality Index | -1.5000 change in units on a scale |
Secondary
Change in Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ)
REM sleep behavior disorder screening questionnaire (RBDSQ). The change may be the total scores of RBDSQ. REM sleep behavior disorder screening questionnaire (RBDSQ) - is a 10-item, patient self-rating instrument assessing the participant's sleep behavior with short questions that have to be answered by either yes or no. Items 1 to 4 address the frequency and content of dreams and their relationship to nocturnal movements and behavior. Item 5 asks about self-injuries and injuries of the bed partner. Item 6 consists of four sub items assessing nocturnal motor behavior more specifically, e.g., questions about nocturnal vocalization, sudden limb movements, complex movements, or bedding items that fell down. Items 7 and 8 deal with nocturnal awakenings. Item 9 focuses on disturbed sleep in general and item 10 on the presence of any neurological disorder. The maximum total score of the RBDSQ is 13 points. Score ranges 0-13 points. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) | -0.4692 change in units on a scale |
| Placebo | Change in Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ) | -0.3333 change in units on a scale |
p-value: 0.75595% CI: [-1.0028, 0.7312]Mixed Models Analysis
Secondary
Change in Rigidity Sub Scores in MDS UPDRS
Rigidity sub scores in MDS UPDRS. The change may be the sub scores of rigidity related item in MDS UPDRS (item 3.3). Score ranged from 0-20. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Rigidity Sub Scores in MDS UPDRS | -0.3742 change in units on a scale |
| Placebo | Change in Rigidity Sub Scores in MDS UPDRS | -0.6030 change in units on a scale |
p-value: 0.769395% CI: [-1.325, 1.7825]Mixed Models Analysis
Secondary
Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Daytime Sleep (DS) Problems.
Scales for Outcomes in Parkinson's disease (SCOPA) sleep DS subscale is a valid, reliable, short scale for assessing daytime sleep problems (DS) in patients with PD. The sub scale includes six items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-18. The higher the worse.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: 31 patients from CBD group and 30 from placebo group conducted the SCOPA DS scales.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Daytime Sleep (DS) Problems. | -0.5280 change in units on a scale | Standard Error 0.3575 |
| Placebo | Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Daytime Sleep (DS) Problems. | -0.2667 change in units on a scale | Standard Error 0.3769 |
Secondary
Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Nighttime Sleep (NS) Problems.
Scales for Outcomes in Parkinson's disease (SCOPA) sleep NS subscale - is a valid, reliable, short scale for assessing nighttime sleep problems (NS) in patients with PD. The NS sub scale includes five items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-15. The higher the worse.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: 31 patients from CBD group and 30 from placebo group conducted the SCOPA NS scales.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Nighttime Sleep (NS) Problems. | -1.2066 change in units on a scale | Standard Error 0.5075 |
| Placebo | Change in Scales of Outcomes in Parkinson's Disease (SCOPA) - Nighttime Sleep (NS) Problems. | -1.2333 change in units on a scale | Standard Error 0.4074 |
p-value: 0.967495% CI: [-1.2757, 1.3292]Mixed Models Analysis
Secondary
Change in Scales of Outcomes in Parkinson's Disease (SCOPA) Sleep-daytime Sleepiness
Scales for Outcomes in Parkinson's disease (SCOPA)sleep - is a valid, reliable, short scale for assessing daytime sleepiness (DS) and nighttime sleep problems (NS) in patients with PD. The DS sub scale evaluates daytime sleepiness and includes six items with four response options, ranging from 0 (never) to 3 (often). The score ranges 0-18. The higher the worse. The other
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: 31 patients from CBD group and 30 from placebo group conducted the SCOPA DS scales.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Scales of Outcomes in Parkinson's Disease (SCOPA) Sleep-daytime Sleepiness | -0.5280 change in units on a scale |
| Placebo | Change in Scales of Outcomes in Parkinson's Disease (SCOPA) Sleep-daytime Sleepiness | -0.2667 change in units on a scale |
p-value: 0.616795% CI: [-1.3002, 0.7775]Mixed Models Analysis
Secondary
Change in Semantic Verbal Fluency
The change may be the scores of Semantic verbal fluency. Semantic Verbal Fluency - Semantic Verbal fluency is a measure of speeded verbal fluency and word retrieval in which participants are asked to say as many animal names/fruits and vegetables for 60 seconds. The total number of words generated across all three trials is recorded. The higher the score is, the better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 29 participants performed the cognitive test from CBD group, and 29 from placebo group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Semantic Verbal Fluency | 0.7153 change in units on a scale |
| Placebo | Change in Semantic Verbal Fluency | 2.4672 change in units on a scale |
p-value: 0.109395% CI: [-3.9082, 0.4045]Mixed Models Analysis
Secondary
Change in Stanford Sleepiness Scale
Is a quick and easy way to assess how the participant is feeling. The change may be the scores of the scale 3 hours after dosing compared to pre-dosing. Stanford Sleepiness Scale (SSS): The Stanford Sleepiness Scale is a quick and easy way to assess how alert the participant is feeling. SSS is validated and probably the most widely used instrument for the assessment of participant's sleepiness. Score ranges 0-7. Higher values represent a worse outcome.
Time frame: Pre- and 3 hours post- dose at baseline visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Stanford Sleepiness Scale | 0.2903 change in units on a scale |
| Placebo | Change in Stanford Sleepiness Scale | -0.03333 change in units on a scale |
p-value: 0.210395% CI: [-0.188, 0.8353]Mixed Models Analysis
Secondary
Change in Symbol Digit Modalities Test
The change may be the scores of Intellectual functioning estimate, Symbol digit modalities test (SDMT). The SDMT is a measure of processing speed and working memory that has proven to be sensitive to cognitive impairment in MS that has both oral and written trials (only the oral trial will be administered given the anticipated difficulty patients will have with tremor). Participants are presented with a key at the top of a page pairing unique symbols with single digits. Participants are required to provide the correct digit with symbols that are presented on the rest of the page. The score is the number of correctly coded items from 0-110. The number of correct responses provided in 90 seconds on the oral trial is recorded. Scores range 0-110 items. The higher the score the better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 29 participants performed the cognitive test from CBD group, and 29 from placebo group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Symbol Digit Modalities Test | 0.6143 change in units on a scale |
| Placebo | Change in Symbol Digit Modalities Test | 3.8357 change in units on a scale |
p-value: 0.08895% CI: [-6.9381, 0.4953]Mixed Models Analysis
Secondary
Change in The Columbia-Suicide Severity Rating Scale (C-SSRS)
C-SSRS is a suicidal ideation rating scale. The change may be the answers to the questions of C-SSRS. There are five questions and have binary responses (yes/no). Assign a score of 1 if answer yes and score of 0 if no . Higher values represent a worse outcome.The mximum score is 5.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in The Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 score on a scale |
| Placebo | Change in The Columbia-Suicide Severity Rating Scale (C-SSRS) | 0 score on a scale |
Secondary
Change in the Number of Participants With Presence of Seborrheic Dermatitis From Baseline to Final Visit.
Dermatology photography evaluation. The change in number of participants with a presence of seborrheic dermatitis from baseline to final visit. Dermatology photography: take a picture of the central face, as this is the most common area of seborrhea, and send it, with appropriate privacy safeguards, to dermatologists, Dr. Robert Dellavalle, MD., and Dr. Andrea Steel.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in the Number of Participants With Presence of Seborrheic Dermatitis From Baseline to Final Visit. | 2 participants |
| Placebo | Change in the Number of Participants With Presence of Seborrheic Dermatitis From Baseline to Final Visit. | 3 participants |
p-value: 0.440195% CI: [-0.988, 0.4354]Mixed Models Analysis
Secondary
Change in the Timed UP&GO (TUG)
The Timed Up & Go (TUG) test is a physical performance measure in which the ability to rise up from a seated chair position, walk 3m, turn, walk back, and sit down is timed. This measure is useful in an outpatient setting, because it requires only a few minutes, is easy to administer, and requires little equipment. Importantly, the TUG test is highly correlated with functional mobility, gait speed, and falls in older adults. The change may be the time duration (seconds) of performing the task. The higher, the worse.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in the Timed UP&GO (TUG) | -0.5409 seconds |
| Placebo | Change in the Timed UP&GO (TUG) | -0.5922 seconds |
p-value: 0.91595% CI: [-0.9086, 1.0111]Mixed Models Analysis
Secondary
Change in Total Scores on Items 3.17 and 3.18 in MDS-UPDRS
Rest tremor amplitude and constancy of rest tremor scores in MDS UPDRS. The change may be the sum scores of 3.17 and 3.18. Score ranged from 0-24. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Total Scores on Items 3.17 and 3.18 in MDS-UPDRS | -1.1570 change in units on a scale |
| Placebo | Change in Total Scores on Items 3.17 and 3.18 in MDS-UPDRS | -0.1000 change in units on a scale |
Secondary
Change in Unified Dyskinesia Rating Scale
To evaluate involuntary movements often associated with treated PD. The change may be the total scores of the scale, including historical sub-score (0-60) and objective sub-score (0-44). The total score is historical sub score plus objective sub score, ranged from 0- 104. Higher values represent a worse outcome.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: In CBD group, 31 patients at baseline and 29 patients at 2.5 mg/kg/day were testes. In Placebo group, 30 at baseline and 28 at 2.5 mg/kg/day were tested.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Unified Dyskinesia Rating Scale | 1.4704 score on a scale |
| Placebo | Change in Unified Dyskinesia Rating Scale | -1.4270 score on a scale |
Secondary
Change in Vital Signs-heart Rate
The change may be Heart rate (beat/minute) while standing.
Time frame: Baseline; at the end of 2.5 mg/kg/day, through 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Vital Signs-heart Rate | 0.9459 change in beats per minute |
| Placebo | Change in Vital Signs-heart Rate | 0.6326 change in beats per minute |
p-value: 0.897495% CI: [-4.5414, 5.168]Mixed Models Analysis
Secondary
Change in Vital Signs--temperature (Fahrenheit Degree)
The change may be temperature in Fahrenheit degree
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Vital Signs--temperature (Fahrenheit Degree) | -0.3069 change in degrees Fahrenheit |
| Placebo | Change in Vital Signs--temperature (Fahrenheit Degree) | -0.1882 change in degrees Fahrenheit |
p-value: 0.624595% CI: [-0.6019, 0.3644]Mixed Models Analysis
Secondary
Change in Vital Signs--weight
The change may be weight in kilograms or lbs.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Vital Signs--weight | 0.07389 change in kilograms |
| Placebo | Change in Vital Signs--weight | -0.07658 change in kilograms |
p-value: 0.464395% CI: [-0.2882, 0.5892]Mixed Models Analysis
Secondary
Change in Wake After Sleep Onset
WASO, the total number of minutes that a person is awake after having initially fallen asleep; higher numbers are worse.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Wake After Sleep Onset | -48.89 change in minutes |
| Placebo | Change in Wake After Sleep Onset | -1.97 change in minutes |
p-value: 0.112895% CI: [-105.51, 11.68]Mixed Models Analysis
Secondary
Change in Wechsler Test for Adult Reading
The change may be the scores of Wechsler test for Adult Reading. Wechsler Test of Adult Reading (WTAR) - Word reading tests are an established method of establishing a premorbid estimate of verbal intellectual functioning, which will serve as an estimate of premorbid cognitive reserve. The WTAR comprises 50 words with irregular pronunciations that participants read aloud. The raw score can be transformed to an age-adjusted standard score, which is used to predict IQ (M = 100; SD = 15). Scores higher means better.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: Out of the total study population, 25 participants took the cognitive test from CBD group, and 26 from placebo group.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Change in Wechsler Test for Adult Reading | 0.4421 change in units on a scale |
| Placebo | Change in Wechsler Test for Adult Reading | -1.4931 change in units on a scale |
p-value: 0.101695% CI: [-0.4372, 4.3076]Mixed Models Analysis
Secondary
Difference in Proportion of Participants That Discontinue the Study Due to Study Drug Intolerance
Difference in Proportion of participants that discontinue the study due to study drug intolerance. The change may be the number of patients dropped out.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Difference in Proportion of Participants That Discontinue the Study Due to Study Drug Intolerance | 1 Participants |
| Placebo | Difference in Proportion of Participants That Discontinue the Study Due to Study Drug Intolerance | 0 Participants |
Secondary
Difference of Plasma Interleukin 6 Level Between PD and Healthy Control Population
Interleukin 6 is an inflammatory cytokine, and is measured in the blood. Whole bold was collected into tubes containing anticoagulant; tubes were inverted gently 3-4 times. Blood was allowed to clot at room temperature for 30 to 45 min, centrifuged at 1,000 x g for 15 min at 4°C and serum was transferred to a clean polypropylene tube. To completely remove platelets and precipitates, the tubes were centrifuge again at 10,000 x g for 10 min at 4°C. Processed samples were stored at -80°F, and cytokine levels measured using the Bio-Plex ProTM Human Cytokine Assay.
Time frame: From baseline to the end of 2.5 mg/kg/day, assessed up to 3 weeks
Population: PD participants who took either cannabidiol cannabis extract oral solution or placebo.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | Difference of Plasma Interleukin 6 Level Between PD and Healthy Control Population | 2.99 ng/mL |
| Placebo | Difference of Plasma Interleukin 6 Level Between PD and Healthy Control Population | 1.59 ng/mL |
Secondary
The Number of Participants Wtih Liver Function Impairment Related Adverse Events
Liver function impairment will be evaluated and then related to adverse events and documented at each clinic visit. The change may be the frequency and severity of liver function impairment related AEs, including nausea/vomiting, diarrhea, abdominal pain, fatigue, weakness, chills, appetite changes, weight loss or gain, fever, etc.
Time frame: Baseline; at the end of 2.5 mg/kg/day; and every 3-5 days at each dose level, through 3 weeks.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | diarrhea | 2 Participants |
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | anorexia | 2 Participants |
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | fatigue | 10 Participants |
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | weight loss | 1 Participants |
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | abdominal pain | 1 Participants |
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | not applicable | 9 Participants |
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | nausea | 6 Participants |
| Placebo | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | not applicable | 9 Participants |
| Placebo | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | diarrhea | 4 Participants |
| Placebo | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | nausea | 3 Participants |
| Placebo | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | fatigue | 6 Participants |
| Placebo | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | abdominal pain | 3 Participants |
| Placebo | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | anorexia | 3 Participants |
| Placebo | The Number of Participants Wtih Liver Function Impairment Related Adverse Events | weight loss | 2 Participants |
Secondary
The Number of Participants Wtih Treatment-related Adverse Events
Adverse events (AEs) are collected at each dose level. AEs collection include Serious Adverse Events (SAE), withdrawal symptoms and common AEs. SAE is an undesirable medical occurrence that results in death, or life-threatening, or inpatient hospitalization or prolongation of existing hospitalization or significant disability or incapacity or in a congenital anomaly/birth defect. Withdrawal and common AEs include headache, anxiety, nausea/vomiting, tremor, chills, decreased concentration, increased concentration, agitation, irritability, sleep disturbances, mood changes, somnolence, fatigue, anorexia, appetite changes, weight loss or gain, diarrhea, convulsion, abdominal pain, weakness, fever and other unexpected AEs. All of the these AEs will be recorded and counted.
Time frame: Every 3-5 days at each dose level, assessed up to 3 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CBD Cannabis Extract Oral Solution | The Number of Participants Wtih Treatment-related Adverse Events | 26 Participants |
| Placebo | The Number of Participants Wtih Treatment-related Adverse Events | 25 Participants |