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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Restless Legs Syndrome, Insomnia, Sleep Disorder

Intervention / Treatment
-----------------
* Drug: Suvorexant
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment --> Placebo<br>This group will receive suvorexant during the first 4-week phase, and placebo during the second 4-week phase. | Drug: Suvorexant<br>* 10-mg or 20-mg suvorexant capsules<br>* Other names: Belsomra;Other: Placebo<br>* Matching placebo capsules<br>|
| Experimental: Placebo --> Treatment<br>This group will receive placebo during the first 4-week phase, and suvorexant during the second 4-week phase. | Drug: Suvorexant<br>* 10-mg or 20-mg suvorexant capsules<br>* Other names: Belsomra;Other: Placebo<br>* Matching placebo capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actigraphically-Derived Total Sleep Time | Total sleep time as measured by actigraphy | 2 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Suvorexant