A Study of Suvorexant in Patients With Multiple Sclerosis Fatigue and Insomnia

Study Overview
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Brief Summary
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This study assesses the safety, tolerability, and efficacy of suvorexant in multiple sclerosis patients. Enrolled subjects will receive 2 weeks of treatment during treatment period 1 with either suvorexant or matching placebo (1:1). After treatment period 1, subjects will undergo a washout period of 1 week then 2 weeks of the alternate treatment (either suvorexant or placebo). The primary hypothesis is that suvorexant will provide greater improvement in sleep, as measured by symptom rating scales, compared to placebo.

Detailed Description
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The target enrollment number is 30 people with multiple sclerosis who meet inclusion criteria. After informed consent is given, potential subjects will be screened to ensure they meet eligibility criteria. Subjects who meet eligibility criteria will complete baseline assessments and will then be randomized to receive 2 weeks of treatment (Treatment Period 1) with either suvorexant or matching placebo (1:1). The initial dose of suvorexant will be 10 mg at bedtime, with optional titration to 20 mg after 5-7 days. Study drug will be dispensed by an independent research pharmacist, keeping both study staff and the subject blinded. All subjects, whether in placebo or active arm, will receive a wearable sleep monitor to be worn for 7 days at baseline, and during both treatment periods. All subjects will keep 7-day sleep diaries at baseline and during each study period. At the end of Treatment Period 1 (2 weeks), subjects will undergo efficacy assessments with repeated clinical scales. Subjects will then go through a 1-week open-label off-drug washout period. Subjects will then be crossed over into the alternate treatment group, which will once again be double-blinded; those on active treatment (suvorexant) in Treatment Period 1 will be switched to placebo, and those on placebo in Treatment Period 1 will be switched to active treatment. Treatment Period 2 will also be 2 weeks long, and at the end of this, subjects will undergo final assessment with clinical scales.

Official Title
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A Double-blind, Crossover, Placebo-controlled Study to Compare the Effects of Nighttime Administration of Suvorexant in Patients With Multiple Sclerosis Fatigue and Insomnia

Conditions
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Multiple Sclerosis, Fatigue, 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: Diagnosis of multiple sclerosis made at least 3 months prior based on McDonald criteria; Age 18-75 inclusive; Expanded Disability Status Scale (EDSS) 0- 7.5; Clinical stability defined as no multiple sclerosis exacerbation or change in disease modifying therapy for 60 days prior to screening; Screening Fatigue Severity Scale score of ≥4.0; Has Insomnia Disorder defined by diagnostic criteria published in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5); 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; 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; Signed and dated Institutional Review Board-approved informed consent form before any protocol-specific screening procedures have been performed. Exclusion Criteria: Use of potential multiple sclerosis-associated fatigue drugs within 3 days of screening until study completion, including modafinil, armodafinil, amantadine, methylphenidate, products with amphetamine or dextroamphetamine; Use of any of any prohibited medication (including Digoxin, benzodiazepines, barbiturates, opiates, Zolpidem, Zaleplon, Eszopiclone, moderate or strong CYP3A inhibitors, or strong inducers of CYP3A) from 3 days prior to screening to termination visit; Female 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); History of narcolepsy; Has a diagnosis of severe chronic obstructive pulmonary disease (COPD), defined by forced expiratory volume 1 (FEV1) < 50% of predicted on most recent available pulmonary function test (PFT). 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 (OSA), with severe obstructive sleep apnea defined as having an apnea-hypopnea index (AHI) > 30 on prior polysomnograph (PSG). Polysomnograph is not required if there is no history of obstructive sleep apnea; Is concurrently using other central nervous system (CNS) 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. Medical marijuana is allowed if consumed at the patient's usual dose at least 2 hours prior to or 8 hours after taking the study drug. Recreational marijuana is not allowed from screening until end of study; Has evidence at screening of severe hepatic impairment as defined by a Child-Pugh score > 10; Cognitive impairment that in the opinion of the investigator would prevent completion of study procedures or the ability to provide informed consent; Suicidality or severe depression as measured by screening Beck Depression Inventory II (BDI) score > 28 or score of >1 on Beck Depression Inventory II Question 9 (suicidality screen) at any time during the study; Any other serious and/or unstable medical condition.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: randomized cross-over trial of suvorexant and placebo for people with multiple sclerosis (MS), insomnia and fatigue
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Suvorexant<br>Suvorexant - 10 mg (one tablet) taken by mouth once daily at bedtime with option to up-titrate to 20 mg (two tablets) taken by mouth once daily at bedtime. | Drug: Suvorexant<br>* See detailed information in associated Arm Description.<br>* Other names: Belsomra;|
| Placebo Comparator: Placebo<br>Placebo - one tablet taken by mouth once daily at bedtime and two tablets taken by mouth daily at bedtime if subject up-titrates. | Drug: Placebo<br>* Sugar pill manufactured to mimic suvorexant 10 mg tablet.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insomnia Severity Index (ISI) score | 7-question survey assessing symptoms of insomnia over the past week. Maximum score is 28, with higher scores indicating greater severity. | Week 1, Week 3, Week 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Quality of Sleep (sQUAL) | This is a single question, How would you describe the quality of your sleep last night? There are 4 choices to answer: 1= poor, 2 = fair, 3= good, 4= excellent | Week 1, Week 3, Week 7 | 
| Subjective refreshed feeling on waking (sFRESH) | This is a single question, How refreshed do you feel this morning? There are 5 choices to answer: 1 = not at all refreshed, 2 = a little refreshed, 3 = moderately refreshed, 4 = quite a bit refreshed, 5 = extremely refreshed | Week 1, Week 3, Week 7 | 
| Change in Modified Fatigue Index Scale (MFIS) score | This scale has 21 items with physical, cognitive and psychosocial subscales. Subjects will complete the Modified Fatigue Index Scale (MFIS) as the first test conducted on the day of visit. Their ratings on the 21-item questionnaire will be based on their fatigue experience over the previous 1 week. | Week 1, Week 3, Week 7 | 
| Subjective Global Impression of Change | This is a single question: How would you rate change in your level of physical and mental function, during the study? Responses range from Extremely improved, Much improved, Slightly improved, No change, Slightly worse, Much worse, and Extremely worse. | Week 1, Week 3, Week 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Fatigue, Insomnia, Suvorexant, Belsomra, Sleep disorder, Sleep