Parkinson Disease
Conditions
Keywords
Parkinson's disease, Light therapy, Circadian rhythm
Brief summary
Light treatment was originally employed in Parkinson's disease (PD) to determine if it might be effective in treating co-existing symptoms of depression and insomnia. However, a preliminary double-blind study as well as other studies reported significant improvement in both motor and co-existing Parkinsonian symptoms. As of yet, no long term double blind study has validated these findings. This study will use a double-blind design to evaluate the safety and efficacy of a non-invasive light therapy device to be used with ongoing pharmacotherapy for PD, over a six month treatment period.
Detailed description
Parkinson's disease (PD) is traditionally described as a disorder of compromised dopamine (DA) function in the nigro-striatal dopamine (NSD) system. This system extends from the midbrain, through the hypothalamus and into the forebrain to critical areas involved in the control of motor performance. Restoration of DA content in this system by administering the DA precursor L-dopa or DA agonists reinstates motor control, but provides only symptomatic relief with waning efficacy as the disease advances. Symptoms of depression and sleep disturbances are also commonly seen in PD patients, and the manifestation of these symptoms suggests impaired circadian function. Although the involvement of the circadian system in PD was intimated in the first formal account of the disorder provided by James Parkinson, it was not until recently that circadian malfunction has been specifically cited as playing a major role in the development and progression of the disease. In addition to scattered reports depicting circadian-like features of PD and related syndromes, a large body of evidence describes the benefits of light therapy in PD from both the preclinical and clinical perspectives. While the development of a formal understanding has been largely omitted as to the basis for any therapeutic effect exerted by light, recent studies have shown that the nigro-striatal dopamine system is comprised of the same cell type as cells in the retina and the pineal. Such cells are driven by visual input whereby dopamine and melatonin sit in functional opposition to regulate day night activities including sleep, mood, reproduction, anti-oxidation and movement. Hence one may conclude that the circadian system plays a major role in many aspects of PD. Recent work in PD has also suggested that the efficacy of light therapy is mediated by melatonin and dopamine function in the retina. On this basis it would be reasonable to assume that intervention into the function of the circadian system with light therapy in PD patients might well serve to modify the course and consequences of the disease. The present study serves to extend this finding to the point of providing a practical, non-invasive method for helping patients.
Interventions
DEVICESpectramax light therapy device
Spectramax light therapy device emits a specific combination of bandwidths and intensities of light.
DEVICEControl light device
The control light device is identical in appearance to the Spectramax light therapy device, except that when turned on, emits a different combination of bandwidths and intensity, not believed to produce a therapeutic response.
Sponsors
PhotoPharmics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1.Males and females, with Stage II - III, idiopathic Parkinson's disease, as assessed by Hoehn-Yahr Scale * 2\. On an optimized, stable dopamine replacement therapy for at least 1 month
Exclusion criteria
* 1\. Participants younger than 45 years old * 2\. Participation in a study of investigational or marketed drugs or devices during the 30-day period prior to the prospective subject's Baseline Evaluation or during their involvement in this investigation * 3\. Subjects who are medically complicated, medically unstable and/or have other severe co-morbid disease states, as determined by the Investigator. * 4\. History of psychiatric illness that would preclude compliance with the protocol and/or ability to complete the study safely * 5\. History or current diagnosis of major psychiatric disorder including Bipolar I Disorder that could interfere with accurate assessment and effective treatment * 6\. Have a Beck Depression Inventory-II (BDI-II) score of greater than or equal to 14 * 7\. An anticipated need for a change in dopamine replacement therapy during the subject's involvement in the investigation * 8\. Patients on stable anti-depressant dose for less than 6 weeks * 9\. Less than one month since stopping an anti-depressant or psychoactive medication * 10\. History of current or recent (within previous 12 months) alcohol, narcotic or other drug abuse by the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) criteria * 11\. Active suicidal or homicidal ideation or plan as determined by the Investigator or have a score of greater than or equal to 2 on the DBDI-II. * 12\. Previous use of light therapy treatment * 13\. Females of childbearing potential, i.e. capable of becoming pregnant * 14\. Night shift work within the past 6 months or planned during the investigation * 15\. Have planned travel of more than two weeks outside of two time zones from home during involvement in the Investigation * 16\. Planned travel outside of two time zones from home during the last two months of the Subject's involvement in the Investigation * 17\. Current use or use within the previous 1 month of photosensitizing or other medications that in the opinion of the investigator would interfere with the safety of the Subject during the trial including * amiodarone * benoxaprofen * chlorpromazine * demeclocycline * fleroxacin * nalidixic acid * ofloxacin * piroxicam * porfimer * psoralens * quinidine * temoporfin tetracycline * oral isoretinoin (Accutane) * St. John's wort * melatonin * 18\. Have a history of significant eye trauma or disease, retinopathy, and/or cataract of a level that would significantly affect transmission or processing of light through either eye * 19\. Other neurological disorders that in the opinion of the Investigator would interfere with the conduct of the study * 20\. Pre-existing major joint problems that in the opinion of the Investigator would interfere with the conduct of the study * 21\. History of cerebral insult or central nervous system infection that in the opinion of the Investigator would preclude successful participation in Investigation related procedures * 22\. Cognitive impairment, e.g. as determined by the Montreal Cognitive Assessment, that in the opinion of the Investigator would interfere with the conduct of the Investigation * 23\. Focal neurological deficits that in the opinion of the Investigator would interfere with the conduct of the Investigation * 24\. High dopamine replacement therapy (DART) dosage levels or severe dyskinesia attributable to DART that would preclude successful participation in the Investigation related procedures or interventions in the opinion of the site Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Combined Scores (Sum) of Parts I, II, and III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (M (MDS-UPDRS) From Baseline to Endpoint at 6 Months. | Six Months | Part I: Non-motor impact of experiences of daily living. Part I has 13 questions,the first 6 are assessed by the examiner, and the remaining 7 are usually self assessed, but may include the patient's caregiver. Each question = 0-4, range= 0 - 65. Part II: Motor Aspects of Experiences of Daily Living: This portion of the scale assesses the motor impact of PD on patients' experiences of daily living. There are 13 questions which are a component of the self-administered Patient Questionnaire.Each question = 0-4, range = 0-65. Part III: Motor Examination: This portion of the scale assesses the motor signs of PD and is administered by the evaluator. There are 18 questions, however several questions have multiple parts which are also scored. Each question 0-4, Total range=0-132. Higher score=more severe |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Clinical Global Impression- Improvement Scale (CGI-I) From Baseline to Endpoint at 6 Months. | Six months | The Clinical Global Impression of Improvement is an assessment of the clinician's view of the patient's global functioning. Participants are ranked O at baseline. The CGI-I ranks 0 - 7, with 0 being much improved, 4 being neutral, and 7 being much worse. |
| Change in the Score of the Parkinson's Disease Questionnaire - 39 From Baseline to Endpoint at 6 Months | Six months | The 39 question Parkinson's Disease Questionnaire (PDQ-39) is a widely used patient reported rating scale in Parkinson's disease. Respondents affirm if they have experienced problems due to their disease using a five point scale from never (0 points) to always (4 points, or worse) in doing common activities. The PDQ-39 is comprised of 8 domains: mobility, emotion, activities of daily living, cognition, stigma, social support, communication, bodily discomfort. Total possible range of scores = 0 - 156 The questions are divided into eight measurement scales each comprising 3 to 10 questions. The scores for the questions in each scale are totaled and normalized to a scale of 0 - 100, that is equivalent to percent of maximum score. The scales are; Mobility (MOB): Q1-10; Activities of Daily Life (ADL): Q11-16; Emotional Well Being (EMO): Q17-22; Stigma (STI): Q23-26; Social Support (SOC): Q27-29; Cognitions (COG): Q30-33; Communication (COM) Q34-36; and Bodily Discomfort (BOD): Q37-39. |
| Change in the Score of the Parkinson's Disease Sleep Scale-Disturbed Sleep, From Baseline to Endpoint at 6 Months. | Six months | The Parkinson's Disease Sleep Scale 2 (PDSS-2) is designed to assess nocturnal disability in Parkinson's disease. The PDSS-2 is a 15 question analog scale that ranks answers from 0 - 4, with 4 being worse. In addition to an overall assessment of sleep disability three aspects of sleep problems can be obtained; disturbed sleep (total of questions 1-3, 8 and 14), PD-specific nocturnal motor symptoms (total of questions 4-6, 12 and 13), and PD-specific nocturnal symptoms (Total of questions 7, 9-11 and 15). We selected the Disturbed Sleep subscale as a key secondary outcome measure. This subscale has a total range of 0 - 16, with 16 being more severe. |
| Change in the Score of the Epworth Sleepiness Scale From Baseline to Endpoint at 6 Months. | Six months | The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness to help in diagnosing sleep disorders. The ESS questionnaire asks the subject to rate his or her probability of falling asleep on a scale of increasing probability from 0 (none) to 3 (worse) for eight different everyday situations. The total range is 0 - 24, with higher scores representing worse severity. |
Countries
Netherlands, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Spectramax Light Therapy Device Light therapy device which emits a specific bandwidth combination and intensity of light.
Spectramax light therapy device: Spectramax light therapy device emits a specific combination of bandwidths and intensities of light. | 45 |
| Control Light Device Light therapy device, identical in appearance and operation to the Spectramax device, except that it produces a different bandwidth and intensity, which is not believed to produce a therapeutic response.
Control light device: The control light device is identical in appearance to the Spectramax light therapy device, except that when turned on, emits a different combination of bandwidths and intensity, not believed to produce a therapeutic response. | 47 |
| Total | 92 |
Baseline characteristics
| Characteristic | Spectramax Light Therapy Device | Control Light Device | Total |
|---|---|---|---|
| Age, Continuous | 70.3 years STANDARD_DEVIATION 7.94 | 65.9 years STANDARD_DEVIATION 7.55 | 68.0 years STANDARD_DEVIATION 8.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 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 | 45 Participants | 46 Participants | 91 Participants |
| Region of Enrollment Netherlands | 15 Participants | 15 Participants | 30 Participants |
| Region of Enrollment United States | 30 Participants | 32 Participants | 62 Participants |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 29 Participants |
| Sex: Female, Male Male | 33 Participants | 30 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 45 | 2 / 47 |
| serious Total, serious adverse events | 3 / 45 | 1 / 47 |
Outcome results
Primary
Change in the Combined Scores (Sum) of Parts I, II, and III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (M (MDS-UPDRS) From Baseline to Endpoint at 6 Months.
Part I: Non-motor impact of experiences of daily living. Part I has 13 questions,the first 6 are assessed by the examiner, and the remaining 7 are usually self assessed, but may include the patient's caregiver. Each question = 0-4, range= 0 - 65. Part II: Motor Aspects of Experiences of Daily Living: This portion of the scale assesses the motor impact of PD on patients' experiences of daily living. There are 13 questions which are a component of the self-administered Patient Questionnaire.Each question = 0-4, range = 0-65. Part III: Motor Examination: This portion of the scale assesses the motor signs of PD and is administered by the evaluator. There are 18 questions, however several questions have multiple parts which are also scored. Each question 0-4, Total range=0-132. Higher score=more severe
Time frame: Six Months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Spectramax Light Therapy Device | Change in the Combined Scores (Sum) of Parts I, II, and III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (M (MDS-UPDRS) From Baseline to Endpoint at 6 Months. | -17.7 units on a scale | Standard Error 2.8 |
| Control Light Device | Change in the Combined Scores (Sum) of Parts I, II, and III of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (M (MDS-UPDRS) From Baseline to Endpoint at 6 Months. | -9.7 units on a scale | Standard Error 3.5 |
Secondary
Change in the Clinical Global Impression- Improvement Scale (CGI-I) From Baseline to Endpoint at 6 Months.
The Clinical Global Impression of Improvement is an assessment of the clinician's view of the patient's global functioning. Participants are ranked O at baseline. The CGI-I ranks 0 - 7, with 0 being much improved, 4 being neutral, and 7 being much worse.
Time frame: Six months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Spectramax Light Therapy Device | Change in the Clinical Global Impression- Improvement Scale (CGI-I) From Baseline to Endpoint at 6 Months. | -0.6 units on a scale | Standard Error 0.1 |
| Control Light Device | Change in the Clinical Global Impression- Improvement Scale (CGI-I) From Baseline to Endpoint at 6 Months. | -0.2 units on a scale | Standard Error 0.1 |
Secondary
Change in the Score of the Epworth Sleepiness Scale From Baseline to Endpoint at 6 Months.
The Epworth Sleepiness Scale (ESS) is a scale intended to measure daytime sleepiness to help in diagnosing sleep disorders. The ESS questionnaire asks the subject to rate his or her probability of falling asleep on a scale of increasing probability from 0 (none) to 3 (worse) for eight different everyday situations. The total range is 0 - 24, with higher scores representing worse severity.
Time frame: Six months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Spectramax Light Therapy Device | Change in the Score of the Epworth Sleepiness Scale From Baseline to Endpoint at 6 Months. | -1.4 units on a scale | Standard Error 0.6 |
| Control Light Device | Change in the Score of the Epworth Sleepiness Scale From Baseline to Endpoint at 6 Months. | 0.1 units on a scale | Standard Error 0.5 |
Secondary
Change in the Score of the Parkinson's Disease Questionnaire - 39 From Baseline to Endpoint at 6 Months
The 39 question Parkinson's Disease Questionnaire (PDQ-39) is a widely used patient reported rating scale in Parkinson's disease. Respondents affirm if they have experienced problems due to their disease using a five point scale from never (0 points) to always (4 points, or worse) in doing common activities. The PDQ-39 is comprised of 8 domains: mobility, emotion, activities of daily living, cognition, stigma, social support, communication, bodily discomfort. Total possible range of scores = 0 - 156 The questions are divided into eight measurement scales each comprising 3 to 10 questions. The scores for the questions in each scale are totaled and normalized to a scale of 0 - 100, that is equivalent to percent of maximum score. The scales are; Mobility (MOB): Q1-10; Activities of Daily Life (ADL): Q11-16; Emotional Well Being (EMO): Q17-22; Stigma (STI): Q23-26; Social Support (SOC): Q27-29; Cognitions (COG): Q30-33; Communication (COM) Q34-36; and Bodily Discomfort (BOD): Q37-39.
Time frame: Six months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Spectramax Light Therapy Device | Change in the Score of the Parkinson's Disease Questionnaire - 39 From Baseline to Endpoint at 6 Months | -1.3 units on a scale | Standard Error 2.1 |
| Control Light Device | Change in the Score of the Parkinson's Disease Questionnaire - 39 From Baseline to Endpoint at 6 Months | 4.3 units on a scale | Standard Error 1.7 |
Secondary
Change in the Score of the Parkinson's Disease Sleep Scale-Disturbed Sleep, From Baseline to Endpoint at 6 Months.
The Parkinson's Disease Sleep Scale 2 (PDSS-2) is designed to assess nocturnal disability in Parkinson's disease. The PDSS-2 is a 15 question analog scale that ranks answers from 0 - 4, with 4 being worse. In addition to an overall assessment of sleep disability three aspects of sleep problems can be obtained; disturbed sleep (total of questions 1-3, 8 and 14), PD-specific nocturnal motor symptoms (total of questions 4-6, 12 and 13), and PD-specific nocturnal symptoms (Total of questions 7, 9-11 and 15). We selected the Disturbed Sleep subscale as a key secondary outcome measure. This subscale has a total range of 0 - 16, with 16 being more severe.
Time frame: Six months
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Spectramax Light Therapy Device | Change in the Score of the Parkinson's Disease Sleep Scale-Disturbed Sleep, From Baseline to Endpoint at 6 Months. | -0.0 units on a scale | Standard Error 0.6 |
| Control Light Device | Change in the Score of the Parkinson's Disease Sleep Scale-Disturbed Sleep, From Baseline to Endpoint at 6 Months. | 0.7 units on a scale | Standard Error 0.5 |