Suvorexant on Sleep Disturbance in Patients With Chronic Insomnia and Suboptimally Controlled Type 2 Diabetes

Study Overview
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Brief Summary
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The investigators aim to determine the effect of suvorexant on subjective total sleep time (TST) in suboptimally controlled Type 2 diabetics with chronic insomnia in a randomized placebo-controlled trial for 3 months.

Detailed Description
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Type 2 diabetes results from a progressive insulin secretory defect on the background of insulin resistance and is a growing pandemic and a leading cause of morbidity and mortality. Sleep disturbance is one of the underappreciated and important features of Type 2 diabetes, and may contribute to the development of the disease. In those with established Type 2 diabetes, there is emerging evidence from cross-sectional studies that sleep disturbance affects glycemic control. Although cross-sectional studies suggest a relationship between sleep disturbance and glycemic control in Type 2 diabetes, causality is best investigated by interventional studies. Suvorexant has a comparatively benign side effect profile compared to many of the hypnotic agents typically prescribed for insomnia. The investigators aim to determine the effect of suvorexant on subjective total sleep time (TST), as well as subjective wake after sleep onset, Insomnia Severity Index, HbA1c levels and insulin sensitivity, inflammatory markers, and other subjective sleep endpoints.

Official Title
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Effect of Suvorexant on Sleep Disturbance in Patients With Chronic Insomnia and Suboptimally Controlled Type 2 Diabetes: A Randomized 3-month Clinical Trial Using a Sequential Parallel Comparison Design

Conditions
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Type 2 Diabetes Mellitus, Insomnia, Sleep Disorder, Inflammation

Intervention / Treatment
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* Drug: Suvorexant
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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 25-75 years Diagnosis of Type 2 diabetes with suboptimally controlled blood sugar determined by HbA1c > 6.5% (and < 10.0%) at both the screening and randomization visits No changes in diabetes medication in the previous month DSM-5 criteria for Insomnia Disorder Score on the Insomnia Severity Index (ISI) measure >10, indicating at least a moderate level of insomnia symptoms2 Report a total sleep time ≤ 6.5 hours and combined sleep onset latency (SOL) 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. Combined SOL and 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: Sleep and medical factors: Diagnosis of severe obstructive sleep apnea not using CPAP (can be included if CPAP adherent), or other untreated primary sleep disorders (e.g. narcolepsy, moderate to severe restless legs syndrome) Shift workers Use of hypnotic medications more than twice per week in the past month Unwillingness to not use sedative-hypnotics (other than suvorexant) during the study period Unwillingness to maintain stable diabetes medication during the study unless medically indicated Positive urine toxic screen for any drugs of abuse other than marijuana at Screening Visit HbA1c ≥ 10.0% at either the screening or randomization visit Psychiatric factors: Current major depressive episode, by report and as indicated by the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR). Subjects with active or unstable major psychiatric disorder, who, in the investigator's judgement, require further treatment. Current alcohol/substance use disorder Medical factors: Renal or hepatic disease judged to interfere with drug metabolism and excretion Pregnant 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 Lifestyle and other factors: Travel across two time-zones during the week prior to enrollment Greater than 6 cups of coffee per day

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Sequential Parallel Comparison Design: subjects will be randomized in a 1:2 ratio to suvorexant 10-20 mg or equivalent placebo for six weeks, followed by re-randomization of placebo non-responders to either suvorexant or placebo in a 1:1 design for six weeks.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment Group<br> | Drug: Suvorexant<br>* 10-mg or 20-mg Suvorexant capsules<br>* Other names: Belsomra;|
| Placebo Comparator: Placebo Responders<br> | Other: Placebo<br>* Matching placebo capsules<br>|
| Active Comparator: Placebo Non-responders Re-randomized to Treatment<br> | Drug: Suvorexant<br>* 10-mg or 20-mg Suvorexant capsules<br>* Other names: Belsomra;Other: Placebo<br>* Matching placebo capsules<br>|
| Placebo Comparator: Placebo Non-responders Re-randomized to Placebo<br> | Other: Placebo<br>* Matching placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Total Sleep Time | Total sleep time as reported on daily sleep diaries | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Wake After Sleep Onset | Total time awake after sleep onset as reported on daily sleep diaries | 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 |