PTSD
Conditions
Keywords
PTSD, CBD, Nantheia ATL5, Quality of Life, Mobility, Tolerability, Cannabidiol
Brief summary
Post-traumatic stress disorder (PTSD) is a psychiatric disorder than may develop following a traumatic event including serious incidents, natural or human-caused disasters, violence, death of a loved one, receipt of traumatic news, or serious illness/hospitalization. While half of US adults experience trauma in their lifetime, most do not develop PTSD. However, those who do develop the disorder may have significant impairments and risk for functional dysfunction across multiple domains. While short term symptoms are the most common, some individuals develop chronic PTSD. These individuals may experience frightening and intrusive thoughts and memories of the event (flashbacks), have sleep disturbances, feel numb or detached, and be easily startled (hypervigilance). This trial is a double-blind placebo controlled study of cannabidiol (CBD) for symptoms of PTSD in adults using liquid structure Formulation (Nantheia ATL5). Participants complete three weeks of baseline data collection including assessments of activity and sleep. Intervention is Nantheia ATL5 or placebo. Dose is initiated at 400mg BID and maintained over 8 weeks. Standardized symptom profile measurements, clinician assessments, laboratory testing, and suicide screening is completed throughout.
Detailed description
Post-traumatic stress disorder (PTSD) is a psychiatric disorder than may develop following a traumatic event including serious incidents, natural or human-caused disasters, violence, death of a loved one, receipt of traumatic news, or serious illness/hospitalization. While half of US adults experience trauma in their lifetime, most do not develop PTSD. However, those who do develop the disorder may have significant impairments and risk for functional dysfunction across multiple domains. While short term symptoms are the most common, some individuals develop chronic PTSD. These individuals may experience frightening and intrusive thoughts and memories of the event (flashbacks), have sleep disturbances, feel numb or detached, and be easily startled (hypervigilance). This trial is a single-site phase II, double-blind, placebo-controlled study of Nantheia ATL5 to study symptoms of Post-Traumatic Stress Disorder (PTSD) in adults. Participants will meet criteria for PTSD using the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Clinical Assessment of Pragmatics (CAPs-5) of ≥ 27. Suicidality is assessed using the Columbia Suicide Severity Rating Scale-Revised (CSSRS-R) at all study visits. Baseline psychopharmacotherapy and/or psychotherapy must be stable (unchanged) for 4 weeks prior to enrollment and should remain unchanged during study treatment. Effects of Nantheia ATL5 on self-reported quality of life (overall and health-related); functional status measurements of personal mobility and risk, and sleep dysfunction; neurobiological biomarkers of threat response (optional functional magnetic resonance imaging: fMRI), and serum inflammatory biomarkers (hs-CRP) implicated in PTSD pathophysiology will be assessed for those participants who had these procedures completed prior to protocol v7.0. Efficacy and tolerability will be assessed throughout intervention. Serum pregnancy (for participants of child bearing potential), urine drug screening, complete blood count (CBC), and Comprehensive Metabolic Panel are completed at every on-site visit. Baseline characteristics of participants with PTSD will be evaluated overall and relative to participants without PTSD (healthy population) during a 3-week baseline period prior to randomization \[Nantheia ATL5 or placebo (PBO)\]. Participants with PTSD will be randomized 1:1 to Nantheia ATL5 or placebo (PBO). Study drug dose is initiated at 400mg BID and maintained for 8 weeks. Study drug is then withdrawn, and one week later safety measures including laboratory testing, assessment of AE's and CSSRS-R are repeated.
Interventions
DRUGCannabidiol Administered as Nantheia ATL5
Participants will take 4 gel capsules twice daily containing 100mg of Nantheia ATL5.
DRUGPlacebo
Participants will take 4 matching gel capsules twice daily containing no active drug.
Sponsors
University of Nebraska
Ananda Scientific
University of Texas at Austin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants and study personnel are blinded to treatment assignment. Randomization will occur in blocks based on self-reported marijuana use (yes/no). Randomization schedule will be provided by the statistician to the research pharmacist for study drug dispensing.
Intervention model description
Double-Blind Placebo Controlled Study
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Ability and willingness to provide informed consent * Stated willingness to comply with all study procedures and availability for duration of the study * Aged 21-65 years * Able to read and communicate in English * Tetrahydrocannabinol (THC) use less than 3 days per week * Meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for a current diagnosis of Post-Traumatic Stress Disorder (PTSD) on the Mini-Mental State examination (MMS), with symptoms present for at least 1 month * Clinician administered Clinical Assessment of Pragmatics (CAPs) score ≥27 at study enrollment and start of Cannabidiol (CBD) observation * Stable psychopharmacologic and/or psychotherapeutic intervention for 4 weeks prior to enrollment
Exclusion criteria
* Current use of prescribed or commercially available CBD products, including Epidiolex® * Suicidal ideation (as defined by answer of "yes" to item 4 or 5 on the baseline Columbia Suicide Severity Rating Scale (C-SSRS) or attempt within 6 months prior to enrollment) * Cognitive impairment in the clinical judgment of the investigator that would impact ability to complete study assessments or confound study results (e.g., neurodegenerative condition or other) * Meets criteria for substance or alcohol use disorder of moderate or greater severity within 6 months prior to study enrollment based on the Mini-Mental State examination (MMS); nicotine dependence permitted * Self-reported cannabis use on \> 3 days/week starting 4 weeks prior to enrollment * Positive urine drug screen for illicit substances other than cannabis * Pregnant \[confirmed by serum human chorionic gonadotropin (hCG) test\], or breastfeeding * Co-morbid medical conditions or concomitant treatments that may adversely impact ability to participate in the trial in the clinical judgment of the investigator \[e.g., significant immunosuppression due to active chemotherapy, recent organ transplant, uncontrolled diabetes, glomerular filtration rate (GFR) \< 25ml/min or on dialysis, recent acute myocardial infarction (MI), Class IV heart failure, or taking any high-risk drugs for drug-drug interactions\] * Treatment with another investigational drug or other intervention within 3 months prior to enrollment * History of psychosis (schizophrenia, schizophreniform disorder, schizoaffective disorder, or substance induced psychosis), active bipolar disorder, or borderline personality disorder diagnosed by a mental health professional * History of open head injury * Self-report of exposure to trauma within 30 days prior to enrollment * Active military service in the 30 days prior to enrollment * Inpatient psychiatric hospitalization within 6 months prior to enrollment * Seizure in the last 6 months * Use of concomitant anti-viral human immunodeficiency virus (HIV) medications (PrEP permitted) * Index trauma before age 18 and no other traumatic experiences which could relate/identify as part of PTSD * History of allergic reaction or significant adverse events (AE) related to cannabis, CBD, or THC * Currently involved in events giving rise to PTSD * Alanine transaminase (ALT)/Aspartate transaminase (AST)/Bilirubin \> 2 x upper limit of normal (ULN) at screening (abnormalities on the comprehensive metabolic panel or complete blood count deemed to be of clinical significance in the judgement of the investigator and clinical team will be evaluated in the clinical context of the participant's history and physical examination to determine eligibility and testing may be repeated if clinically appropriate at the discretion of the investigator) * Refusal to use at least one form of birth control throughout study participation \[including, but are not limited to, male or female condoms, diaphragm, or cervical cap (all with or without spermicide) abstinence, or hormonal/implanted birth control, e.g., pill, injection, intra-uterine device (IUD), implant\] by participants who can become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-traumatic Stress Disorder Symptom Rating | Baseline and 8 weeks | Structured clinician-administered rating of post-traumatic stress disorder (PTSD) symptoms' severity using the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; CAPS-5) Scale. This instrument assesses 20 PTSD symptoms. Each symptom is scored 0 - 4, then symptom scores are totaled. Higher scores indicate greater symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-traumatic Stress Disorder Symptom Symptom Cluster Rating | Baseline and 8 weeks | The cluster scores (symptom domains) are subscales of the CAPS-5 (outcome 1). The CAPS-5 has 20 items, each scored 0-4. The sum of items 1-5 represent cluster B (intrusion symptoms); items 6-7 represent cluster C (avoidance symptoms); items 8-14 represent cluster D (cognitions and mood symptoms); and items 15-20 represent cluster E (arousal and reactivity symptoms). Score ranges are: Cluster B 0-20, Cluster C 0-8, Cluster D 0-28, and Cluster E 0-24. The total of the cluster scores (B+C+D+E) is the total CAPS-5 score. Higher scores indicate greater symptom severity. |
| Post-traumatic Stress Disorder Symptom Rating (Self-reported) | Baseline and 8 weeks | Self-reported rating of post-traumatic stress disorder (PTSD) symptom severity using the PTSD Checklist for DSM-5 (PCL-5). This instrument the 20 items corresponding to the DSM-5 symptom criteria for PTSD. Each item is scored 0 - 4, then symptom scores are totaled. Higher scores indicate greater symptom severity. |
| Clinical Global Impression Post-traumatic Stress Disorder - Severity | Baseline and 8 weeks | Clinical Global Impression Post-traumatic Stress Disorder (PTSD) Symptom Severity (CGI-S) is the assessment by clinicians of the severity of PTSD symptoms based on their experience with adults with PTSD. The CGI-S is scored on a scale of 0 to 7 (0 is "not assessed," 1 is "very much improved and 7 is "very much worse.") Higher scores indicate Higher scores indicate more severe illness. |
| Clinical Global Impression - Improvement | Baseline and 8 weeks | Clinical Global Impression-Improvement (CGI-I) is the assessment by clinicians of the degree of post-traumatic stress disorder (PTSD) symptom improvement based on their experience with the population. It is rated without regard for relatedness to study treatment. The CGI-I is rated on a scale of 0 to 7 (0 is "not assessed," 1 is "very much improved and 7 is"very much worse.") Higher scores indicate worsening of symptoms. |
| Anxiety Severity Rating | Baseline and 8 weeks | Clinician-rated assessment of anxiety symptoms using the Hamilton Anxiety Rating Scale (HAM-A). This instrument assesses 14 psychic (mental agitation and psychological distress) and somatic (related physical complaints) anxiety items. Each item is scored from 0 - 4, then symptom scores are totaled. Higher scores indicate greater anxiety severity. |
| Depression Symptoms Rating | Baseline and 8 weeks | Clinician-rated assessment of depressive symptoms using the Hamilton Depression Rating Scale (HAM-D). This instrument assesses mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. Each item is scored on a 3 or 5 point scale, depending on the item, then item scores are totaled. Higher scores indicate greater depressive symptoms. |
| Global Functioning Disability Questionnaire | Baseline and 8 weeks | Participant-reported assessment of global functioning (an individual's overall ability to cope with daily life and maintain social, occupational, and psychological well-being) using the Sheehan Disability Scale (SDS). This instrument assesses functional impairment in work/school, social life, and family/home life. Each area is scored 0 - 10, then area scores are totaled. Higher scores indicate greater functioning disability. |
| Quality of Life Health Survey | Baseline and 8 weeks | Participant-reported measure of quality of life using the Short Form 36-Item Health Survey (SF-36). This instrument assesses physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Each item is scored 0 - 100, then item scores are totaled. Higher scores indicate greater better health. |
Countries
United States
Contacts
CONTACTBrigette S Vaughan, MSN
PRINCIPAL_INVESTIGATORMatthew Rizzo, MD
University of Nebraska
Outcome results
None listed