A Pilot Study of Suvorexant for Insomnia in Parkinson Disease

Phase 4

Completed

Conditions: Insomnia

Interventions: Drug: Suvorexant
Drug: Placebo

Registration Number: NCT02729714

Lead Sponsor: Burdick, Daniel, M.D.

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Suvorexant or Placebo	Placebo	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
Placebo or Suvorexant	Placebo	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.
Placebo or Suvorexant	Suvorexant	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.
Suvorexant or Placebo	Suvorexant	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

Primary Outcome Measures

Name	Time	Method
Change in Sleep Efficiency as Measured by Polysomnogram	4 weeks	Sleep efficiency is defined as total sleep time divided by total time in bed, expressed as a percent. Polysomnograms were performed at baseline, end of treatment period 1, and end of treatment period 2. A positive change indicates improvement in sleep efficiency. Assessing difference between change in sleep efficiency during suvorexant period and change in sleep efficiency during placebo period.

Secondary Outcome Measures

Name	Time	Method
Subject's Global Impression of Change (SGI-C)	4 weeks	The Subject's Global Impression of Change (SGI-C) is a rating scale that asks 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. Evaluated at end of treatment period 1 and end of treatment period 2.
Latency to Persistent Sleep (LPS)	4 weeks	Latency to Persistent Sleep (LPS) is defined as total time between lights out and first epoch of sleep. Measured on polysomnogram performed at baseline, end of treatment period 1, and end of treatment period 2. A negative change indicates improvement in LPS.
Insomnia Severity Index (ISI)	4 weeks	The Insomnia Severity Index (ISI) is a 7-question survey assessing symptoms of insomnia. Scores range from 0 to 28, with higher scores indicating greater severity. Thus, a negative change in the ISI score indicates improvement in sleep. Performed at baseline, end of treatment period 1, start of treatment period 2, and end of treatment period 2.
Wakefulness After Sleep Onset (WASO)	4 weeks	Wakefulness after sleep onset (WASO) is defined as total time spent awake after first epoch of sleep and before final awakening. Captured during polysomnograms performed at baseline, end of treatment period 1, and end of treatment period 2. Measured in minutes. A negative change indicates improvement in WASO.
Clinician's Global Impression of Change (CGI-C)	4 weeks	The Clinician's Global Impression of Change (CGI-C) is a rating scale that asks the single 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 worse.
Epworth Sleepiness Scale (ESS)	4 weeks	The Epworth Sleepiness Scale (ESS) is an 8-question survey assessing symptoms of daytime sleepiness. Scores range from 0 to 24, with higher scores indicating greater severity of daytime sleepiness. Thus, a negative change indicates improvement in daytime sleepiness. The ESS has been validated for use in the general population and in PD. Administered at start of treatment period 1, end of treatment period 1, start of treatment period 2, and end of treatment period 2.