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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03110315

Acronym

DREAM

Enrollment

Registered

2017-04-12

Start date

2017-03-28

Completion date

2022-03-21

Last updated

2025-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fatigue, Insomnia, Multiple Sclerosis

Keywords

Multiple Sclerosis, Fatigue, Insomnia, Suvorexant, Belsomra, Sleep disorder, Sleep

Brief summary

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

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.

Interventions

DRUGSuvorexant

See detailed information in associated Arm Description.

DRUGPlacebo

Sugar pill manufactured to mimic suvorexant 10 mg tablet.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

investigator is blinded to randomization and results until study completion

Intervention model description

randomized cross-over trial of suvorexant and placebo for people with multiple sclerosis (MS), insomnia and fatigue

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in Insomnia Severity Index (ISI) Score	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

Secondary

Measure	Time frame	Description
Change in Modified Fatigue Index Scale (MFIS) Score	Change from Baseline to 2 Weeks	This scale has 21 items with physical, cognitive and psychosocial questions regarding their fatigue levels. 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. Each question is on a scale from 0 to 4. Higher scores represent worse fatigue. Minimum score is 0 and maximum score is 84.
Patient Global Impression of Change	Change from Baseline to 2 Weeks	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. Higher score indicates improvement. Scale is 0-5 given responses. 0 is minimum, 5 is maximum.
Fatigue Visual Analog Scale	Change from Baseline to 2 Weeks	0-100 scale rating fatigue with 0 being not fatigued at all, 100 being fatigue as bad as can be. Patients are instructed to place an X on the scale based on their overall level of fatigue. On the low-end of the scale are feelings of being awake and alert, having high-energy and vigor. On the high end of the scale are feelings of tiredness, drowsiness, sluggishness, low-energy, lassitude.

Other

Measure	Time frame	Description
Sleep Latency	Change from Baseline to 2 Weeks	A measure of minutes between being awake and falling asleep.
Subjective Quality of Sleep (sQUAL)	Change from Baseline to 2 Weeks	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. 1 is Minimum, 4 is maximum. A higher score means a better outcome.

Countries

United States

Participant flow

Recruitment details

36 subjects were enrolled

Pre-assignment details

Subjects were randomized 1:1 to 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 or matching placebo. The subjects crossed over to opposite treatment for two weeks following a 1-week washout

Participants by arm

Arm	Count
Suvorexant Followed by Placebo 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. After one week washout, Placebo - one tablet taken by mouth once daily at bedtime and two tablets taken by mouth daily at bedtime if subject up-titrates. Suvorexant: See detailed information in associated Arm Description. Placebo: Sugar pill manufactured to mimic suvorexant 10 mg tablet.	18
Placebo Followed by Suvorexant Placebo - one tablet taken by mouth once daily at bedtime and two tablets taken by mouth daily at bedtime if subject up-titrates. After one week washout, 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. Suvorexant: See detailed information in associated Arm Description. Placebo: Sugar pill manufactured to mimic suvorexant 10 mg tablet.	18
Total	36

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	Suvorexant Followed by Placebo	Placebo Followed by Suvorexant	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	3 Participants	3 Participants	6 Participants
Age, Categorical Between 18 and 65 years	15 Participants	15 Participants	30 Participants
Age, Continuous	50.333 years STANDARD_DEVIATION 13.412	55.118 years STANDARD_DEVIATION 10.775	52.657 years STANDARD_DEVIATION 12.616
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants	18 Participants	35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Region of Enrollment United States	18 participants	18 participants	36 participants
Sex: Female, Male Female	12 Participants	12 Participants	24 Participants
Sex: Female, Male Male	6 Participants	6 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 35	0 / 35
other Total, other adverse events	7 / 35	1 / 35
serious Total, serious adverse events	0 / 35	0 / 35

Outcome results

Primary

Change in Insomnia Severity Index (ISI) Score

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