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

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03818581

Collaborator

(none)

107

Enrollment

Location

Arms

30.1

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Insomnia Sleep Disorder Inflammation	Drug: Suvorexant Other: Placebo	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

107 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention 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.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 (Participant, Investigator)

Masking Description:

The participant, investigator, and clinical research coordinator will remain masked throughout the duration of the study. An unmasked research coordinator will be responsible for assessing mid-point outcomes on the sleep diaries and communicating with the pharmacy for re-randomization medication orders.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 15, 2019

Anticipated Primary Completion Date :

Sep 15, 2021

Anticipated Study Completion Date :

Sep 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Treatment Group	Drug: Suvorexant 10-mg or 20-mg Suvorexant capsules Other Names: Belsomra
Placebo Comparator: Placebo Responders	Other: Placebo Matching placebo capsules
Active Comparator: Placebo Non-responders Re-randomized to Treatment	Drug: Suvorexant 10-mg or 20-mg Suvorexant capsules Other Names: Belsomra Other: Placebo Matching placebo capsules
Placebo Comparator: Placebo Non-responders Re-randomized to Placebo	Other: Placebo Matching placebo capsules

Outcome Measures

Primary Outcome Measures

Subjective Total Sleep Time [2 weeks]
Total sleep time as reported on daily sleep diaries

Secondary Outcome Measures

Subjective Wake After Sleep Onset [2 weeks]
Total time awake after sleep onset as reported on daily sleep diaries
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 75 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 25-75 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