Efficacy of Suvorexant in Patients With Effectively Treated Restless Legs Syndrome and Persistent Chronic Insomnia

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04706091

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Location

Arms

21.6

Anticipated Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The investigators aim to determine the effect of suvorexant on actigraphically-derived total sleep time in patients with effectively treated restless legs syndrome with persistent insomnia in a two-arm, double-blind, randomized placebo-controlled crossover 2.5-month trial.

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome Insomnia Sleep Disorder	Drug: Suvorexant Other: Placebo	Phase 4

Detailed Description

Restless Legs Syndrome (RLS) is a sensory-motor neurological disorder characterized by an irresistible urge to move the legs. Persistent difficulties with all phases of sleep are common in patients whose RLS symptoms are resolved with treatment. Multiple potential causes for treatment-refractory sleep disturbance exist, including activating effects of dopamine agonists (which are first-line RLS treatments), conditioned insomnia and poor sleep habits as a result of chronic RLS-related sleep disturbance, and comorbid medical and psychiatric illness. Suvorexant provides an important therapeutic option to treat insomnia in the context of RLS. It has demonstrated long-term efficacy, particularly in shortening the duration of nocturnal awakenings and increasing total sleep time. Similarly, it has a comparatively benign side effect profile compared to many other agents typically prescribed to treat insomnia. The investigators aim to determine the effect of suvorexant on actigraphically-derived total sleep time, as well as actigraphically-derived wake after sleep onset, Insomnia Severity Index score, subjective sleep endpoints, and RLS symptom severity.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Subjects will be randomized in a 1:1 ratio to suvorexant 10-20 mg or equivalent placebo for four weeks followed by crossover (after a 2-week washout) to the alternate treatment.Subjects will be randomized in a 1:1 ratio to suvorexant 10-20 mg or equivalent placebo for four weeks followed by crossover (after a 2-week washout) to the alternate treatment.

Masking:

Double (Participant, Investigator)

Masking Description:

The participant, investigator, and clinical research coordinator will remain masked throughout the duration of the study.

Primary Purpose:

Treatment

Official Title:

Efficacy of Suvorexant in Patients With Effectively Treated Restless Legs Syndrome and Persistent Chronic Insomnia: A Randomized Placebo-Controlled Crossover Trial

Actual Study Start Date :

Aug 12, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment --> Placebo This group will receive suvorexant during the first 4-week phase, and placebo during the second 4-week phase.	Drug: Suvorexant 10-mg or 20-mg suvorexant capsules Other Names: Belsomra Other: Placebo Matching placebo capsules
Experimental: Placebo --> Treatment This group will receive placebo during the first 4-week phase, and suvorexant during the second 4-week phase.	Drug: Suvorexant 10-mg or 20-mg suvorexant capsules Other Names: Belsomra Other: Placebo Matching placebo capsules

Arm

Intervention/Treatment

Experimental: Treatment --> Placebo

This group will receive suvorexant during the first 4-week phase, and placebo during the second 4-week phase.

Drug: Suvorexant

10-mg or 20-mg suvorexant capsules

Other Names:

Belsomra

Other: Placebo

Matching placebo capsules

Experimental: Placebo --> Treatment

This group will receive placebo during the first 4-week phase, and suvorexant during the second 4-week phase.

Drug: Suvorexant

10-mg or 20-mg suvorexant capsules

Other Names:

Belsomra

Other: Placebo

Matching placebo capsules

Outcome Measures

Primary Outcome Measures

Actigraphically-Derived Total Sleep Time [2 weeks]
Total sleep time as measured by actigraphy

Secondary Outcome Measures

Actigraphically-Derived Wake After Sleep Onset [2 weeks]
Wake after sleep onset as measured by actigraphy
Insomnia Severity Index [2 weeks]
A validated tool to measure insomnia severity, on a scale of 0-28, with a higher score representing greater insomnia severity

Other Outcome Measures

Diary-Derived Wake After Sleep Onset [2 weeks]
Wake after sleep onset as reported on daily sleep diaries
Diary-Derived Total Sleep Time [2 weeks]
Total sleep time as reported on daily sleep diaries
Diary-derived Sleep Onset Latency, Sleep Efficiency and Sleep Quality [2 weeks]
Sleep onset latency, sleep efficiency and sleep quality as reported on daily sleep diaries
International Restless Legs Syndrome Study Group Scale [1 week]
A validated tool to measure restless legs syndrome severity, on a scale of 0-40, with a higher score representing greater restless legs syndrome severity

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women of any ethnic origin
Written informed consent is obtained
Speaks and writes in English
A willingness and ability to comply with study procedures
Age 25-85 years
Diagnosis of RLS via Cambridge-Hopkins RLS questionnaire
International Restless Legs Syndrome Study Group scale score (IRLS) < 15
RLS treatment with a dopaminergic agonist or an alpha-2-delta agent
No changes in RLS medication in the previous month
DSM-5 criteria for Insomnia Disorder
Report a total sleep time ≤ 7 hours and wake after sleep onset (WASO) > 45 minutes on 7 or more of the 14 nightly sleep logs during both the initial 2-week screening period and the two-week screening run-in period. WASO does not decrease by more than 50% on the 2-week sleep diary obtained between the screening visit and the randomization visit

Exclusion Criteria:

Diagnosis of moderate/severe obstructive sleep apnea (AHI > 30) not using continuous positive airway pressure therapy (CPAP) (can be included if CPAP adherent), or other untreated primary sleep disorders (e.g. narcolepsy)
Shift workers
Unwillingness to not use sedative-hypnotics (other than suvorexant) during the study period
Unwillingness to maintain stable RLS medication during the study unless medically indicated
Current use of an opiate medication
Unwillingness to not take stimulants (e.g. caffeine) after 4:00 pm during the study
Current major depressive episode, by report and as indicated by the Patient Health Questionnaire (PHQ-9)
Lifetime history of bipolar disorder, psychosis, or other serious psychiatric illness
Current alcohol/substance use disorder
BMI ≥ 40 kg/m^2
Renal or hepatic disease judged to interfere with drug metabolism and excretion
Pregnancy or breastfeeding
Malignancy within past 2 years
Surgery within past 3 months
Neurological disorder or cardiovascular disease raising safety concerns about use of suvorexant and/or judged to interfere with ability to assess efficacy of the treatment
Medical instability considered to interfere with study procedures
Concomitant medications with drug interaction or co-administration concerns
Contraindications or allergic responses to suvorexant
History of being treated with suvorexant
Travel across two time-zones during the week prior to enrollment
Greater than 6 cups of coffee per day