Clinical trial NCT04706091: Efficacy of Suvorexant in Patients With Effectively Treated Restless Legs Syndrome and Persistent Chronic Insomnia
Official title: Efficacy of Suvorexant in Patients With Effectively Treated Restless Legs Syndrome and Persistent Chronic Insomnia: A Randomized Placebo-Controlled Crossover Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Restless Legs Syndrome
Insomnia
Sleep Disorder
Keywords: Suvorexant
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2021-01-12
Enrollment: 46
Sex: ALL
Minimum age (years): 25
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Men or women of any ethnic origin
2. Written informed consent is obtained
3. Speaks and writes in English
4. A willingness and ability to comply with study procedures
5. Age 25-85 years
6. Diagnosis of RLS via Cambridge-Hopkins RLS questionnaire
7. International Restless Legs Syndrome Study Group scale score (IRLS) \< 15
8. RLS treatment with a dopaminergic agonist or an alpha-2-delta agent
9. No changes in RLS medication in the previous month
10. DSM-5 criteria for Insomnia Disorder
11. 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:

1. 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)
2. Shift workers
3. Unwillingness to not use sedative-hypnotics (other than suvorexant) during the study period
4. Unwillingness to maintain stable RLS medication during the study unless medically indicated
5. Current use of an opiate medication
6. Unwillingness to not take stimulants (e.g. caffeine) after 4:00 pm during the study
7. Current major depressive episode, by report and as indicated by the Patient Health Questionnaire (PHQ-9)
8. Lifetime history of bipolar disorder, psychosis, or other serious psychiatric illness
9. Current alcohol/substance use disorder
10. BMI ≥ 40 kg/m\^2
11. Renal or hepatic disease judged to interfere with drug metabolism and excretion
12. Pregnancy or breastfeeding
13. Malignancy within past 2 years
14. Surgery within past 3 months
15. 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
16. Medical instability considered to interfere with study procedures
17. Concomitant medications with drug interaction or co-administration concerns
18. Contraindications or allergic responses to suvorexant
19. History of being treated with suvorexant
20. Travel across two time-zones during the week prior to enrollment
21. Greater than 6 cups of coffee per day

Primary outcomes:
measure: Actigraphically-Derived Total Sleep Time
timeFrame: 2 weeks
Secondary outcomes:
measure: Actigraphically-Derived Wake After Sleep Onset
timeFrame: 2 weeks
measure: Insomnia Severity Index
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: John W Winkelman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: