A Double-blind, Crossover, Placebo-controlled Study to Compare the Effects of Nighttime Administration of Suvorexant in Patients With Multiple Sclerosis Fatigue and Insomnia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Change in Insomnia Severity Index (ISI) Score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
investigator is blinded to randomization and results until study completion
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Suvorexant
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.
干预措施: Suvorexant (Drug)
Placebo
Placebo - one tablet taken by mouth once daily at bedtime and two tablets taken by mouth daily at bedtime if subject up-titrates.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Insomnia Severity Index (ISI) Score
时间窗: Change from Baseline to 2 Weeks
7-question survey assessing symptoms of insomnia over the past week. Maximum score is 28, minimum is 0, with higher scores indicating greater severity. Guidelines for Scoring/Interpretation: Add scores for all seven items = _____ Total score ranges from 0-28 0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate
次要结局
- Change in Modified Fatigue Index Scale (MFIS) Score(Change from Baseline to 2 Weeks)
- Patient Global Impression of Change(Change from Baseline to 2 Weeks)
- Fatigue Visual Analog Scale(Change from Baseline to 2 Weeks)
研究者
Theodore R. Brown, MD MPH
Principal Investigator
EvergreenHealth