A Pilot Study of Suvorexant for Insomnia in Parkinson Disease

Study Overview
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Brief Summary
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The purpose of this study is to see if the study drug, suvorexant, is safe and effective in treating symptoms of insomnia in people with Parkinson's Disease. It is anticipated that a total of 20 subjects, 30 to 80 years of age, with Parkinson's Disease and symptoms of insomnia will participate in the study at this site

Detailed Description
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The proposed study is a randomized, double-blind, placebo-controlled, cross-over trial to assess the safety, tolerability, and efficacy of suvorexant specifically in a cohort of 20 Parkinson's Disease patients between the ages of 30 and 80 (inclusive) who have a complaint of insomnia. After informed consent is given, potential subjects will be screened to ensure they meet eligibility criteria. This will include an overnight polysomnogram, which will serve both as a baseline and a screening polysomnogram. Active drug will be suvorexant 10 mg orally at bed time with an optional up-titration to 15 mg orally at bedtime after 2 weeks. The first treatment period will be 4 weeks long, in which subjects will be randomized 1:1 to receive active drug or matching placebo. At the end of treatment period 1, subjects will undergo efficacy assessment with repeat polysomnogram and clinical scales. This will be followed by a 2-week washout period with placebo; this period only will be single-blinded, as subjects only will be blinded to treatment. Subjects will then be crossed over into the alternate treatment group, which will once again be double-blinded; those on active treatment for period 1 will be switched to placebo, and those on placebo in period 1 will be switched to active treatment. Treatment period 2 will also be 4 weeks long, and at the end of this, subjects will undergo final assessment with polysomnogram and clinical scales.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Suvorexant for Insomnia in Parkinson Disease

Conditions
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Insomnia

Intervention / Treatment
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* Drug: Suvorexant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has signed and dated an Institutional Review Board-approved informed consent form before any protocol-specific screening procedures are performed; Has a diagnosis of Parkinson disease according to the United Kingdom Parkinson Disease Society Brain Bank Criteria; Has a modified Hoehn and Yahr Stage of 1-3, inclusive; Is aged 30-80 years old, inclusive; Has had no change in Parkinson's Disease medications during the 4 weeks preceding screening, with no dose changes during the study, except that as needed doses of carbidopa/levodopa will be allowed to address periodic worsening of parkinsonian symptoms; Is willing and able to complete polysomnogram; Is subject willing and able to limit alcohol use to 1 alcoholic drink per day during the study period and abstain from alcohol for 6 hours prior to each study-related polysomnogram? Is subject willing and able to abstain from caffeine and marijuana for 6 hours prior to and during each study-related polysomnogram Is subject willing and able to abstain from products containing nicotine during each study-related polysomnogram? Has Insomnia Disorder defined by diagnostic criteria published in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition; namely, subject report of all of the following: One of the following: difficulty initiating sleep; difficulty maintaining sleep; or early morning waking; Sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning; Sleep difficulty has occurred on 3 or more nights per week; Sleep difficulty has been present for at least the past 3 months; Sleep difficulty occurs despite adequate opportunity for sleep; Insomnia is not explained by another sleep disorder; Insomnia is not attributable to physiological effects of a consumed substance; On screening polysomnogram, has a latency to persistent sleep > 20 minutes OR total wakefulness after sleep onset > 45 minutes; May use other medications that could influence sleep, other than those specifically prohibited, as long as the dose is stable for 4 weeks preceding screening, with no dose changes during the study; and Has valid health insurance coverage at the time of study enrollment and expects this coverage to remain valid for the duration of the study period. Exclusion Criteria: Is a woman who is breast-feeding, pregnant, or has the potential to become pregnant during the course of the study (fertile and unwilling/unable to use effective contraceptive measures); Does subject have an implanted deep brain stimulator? Has a history of narcolepsy; Has a diagnosis of severe chronic obstructive pulmonary disease, defined by forced expiratory volume in 1 second < 50% of predicted on most recent available pulmonary function test (a pulmonary function test is not required if the subject has never been diagnosed with chronic obstructive pulmonary disease); Has a history of severe obstructive sleep apnea or evidence of severe obstructive sleep apnea on screening polysomnogram, with severe obstructive sleep apnea defined as having an apnea-hypopnea index > 30; Is concurrently using other central nervous system depressants, including alcohol, except that one alcoholic drink per day will be allowed for those with normal hepatic function provided the drink is consumed at least 2 hours prior to or 8 hours after taking the study drug, and no alcohol will be permitted for 24 hours before polysomnogram visits; Is concurrently using digoxin; Is concurrently using any moderate or strong inhibitor of cytochrome P450 3A; Is concurrently using any strong inducer of cytochrome P450 3A; Has evidence at screening of severe hepatic impairment as defined by a Child-Pugh score > 10; Has evidence at screening of severe cognitive impairment as defined by a Montreal Cognitive Assessment score < 15, or has cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent. Has evidence at screening of suicidal ideation in the past 6 months as defined by a positive response to any one of Questions 2-5 on the Columbia Suicide Severity Rating Scale or of a lifetime history of suicidal behavior as defined by any positive response to the suicidal behavior section of the Columbia Suicide Severity Rating Scale.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Suvorexant or Placebo<br>10 Suvorexant or Placebo mg orally at bedtime with an optional up-titration to 15 mg Suvorexant or Placebo orally at bedtime after 2 weeks. The first treatment period will be 4 weeks. Subjects will be randomized 1;1 to receive Suvorexant or matching placebo. Followed by a 2 week washout period with placebo. Subjects will then be crossed over into the alternate treatment group. Subjects on active treatment for period 1 will be switched to placebo, those on placebo in period 1 will switch to Suvorexant | Drug: Suvorexant<br>* 10 mg Suvorexant or matching Placebo orally at bedtime with optional up-titration to 15 mg Suvorexant or matching Placebo orally at bedtime after 2 weeks.<br>* Other names: Belsomra;Drug: Placebo<br>* 10 mg Suvorexant or matching Placebo orally at bedtime with optional up-titration to 15 mg Suvorexant or matching Placebo orally at bedtime after 2 weeks.<br>* Other names: Sugar Pill;|
| Placebo Comparator: Placebo or Suvorexant<br>First treatment period will be 4 week which subjects will be randomized 1;1 with either Suvorexant or placebo. Followed by 2 week washout period with placebo. Subjects will then be crossed over into the alternate treatment group. Subjects on active treatment for period 1 will be switched to placebo, those on placebo in period 1 will switch to Suvorexant. | Drug: Suvorexant<br>* 10 mg Suvorexant or matching Placebo orally at bedtime with optional up-titration to 15 mg Suvorexant or matching Placebo orally at bedtime after 2 weeks.<br>* Other names: Belsomra;Drug: Placebo<br>* 10 mg Suvorexant or matching Placebo orally at bedtime with optional up-titration to 15 mg Suvorexant or matching Placebo orally at bedtime after 2 weeks.<br>* Other names: Sugar Pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Efficiency as measured by Polysomnogram | Polysomnogram defined as total sleep time/ total time in bed. Polysomnogram taken in week 0 (baseline), week 5 and week 11. Assessing change in Polysomnograms at week 5 and at week 11 | week 0, week 5, week 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wake after sleep onset- WASO | Wake after sleep onset is defined as total time spent awake after first epoch of sleep and before final awakening | week 3, week 9, week 15 | 
| Latency to Persistent Sleep- LPS | Latency to Persistent sleep is defined as total time between lights out and first epoch of sleep. | week , week 9, week 15 | 
| Muscle Tonicity | Muscle activity during REM sleep will be recorded as a measure of REM behavior disorder | week 3, week 9, week, 15 | 
| Insomnia Severity Index- ISI | The ISI is a 7-question survey assessing symptoms of insomnia. Maximum score is 28, with higher scores indicating greater severity. The ISI has been validated for use in insomnia research (Bastien 2001). This will be performed at Office Visits 2, 3, 4, and 5, and will be a secondary outcome measure. | week 5, week 9, week, 11, week 15 | 
| Epworth Sleepiness Scale-ESS | The ESS is an 8-question survey assessing symptoms of sleepiness. Maximum score is 24, with higher scores indicating greater severity. The ESS has been validated for use in the general population (Johns 1991) and in PD (Hagell 2007). This will be performed at Office Visits 2, 3, 4, and 5, and will be a secondary outcome measure. | week 5, week 9, week, 11, week 15 | 
| Subject's Global Impression of Change- SGI | The SGIC will be assessed by asking a single question Since baseline (when first starting this study), how have your sleep symptoms changed? Answers will be on a 7-point scale: 1 = much improved; 2 = somewhat improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = somewhat worse; and 7 = much worse. | week 7, week 9, week, 11, week 13, week 15 | 
| Clinicians's Global Impression of Change- CGIC | The CGIC will be assessed by the investigator at week9, week 11, week 15 using a similar question: Since baseline (when first starting this study), how have the subject's sleep symptoms changed? Answers will be on a 7-point scale: 1 = much improved; 2 = somewhat improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = somewhat worse; and 7 = much | week 9, week 11, week 15 |