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

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Type 2 Diabetes Mellitus; Sleep Disorder; Insomnia
• Intervention / Treatment: Other: Placebo; Drug: Suvorexant

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 Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 25-75 years
6. 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
7. No changes in diabetes medication in the previous month
8. DSM-5 criteria for Insomnia Disorder
9. Score on the Insomnia Severity Index (ISI) measure >10, indicating at least a moderate level of insomnia symptoms2
10. 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:

1. Sleep and medical factors:

   1. 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)
   2. Shift workers
   3. Use of hypnotic medications more than twice per week in the past month
   4. Unwillingness to not use sedative-hypnotics (other than suvorexant) during the study period
   5. Unwillingness to maintain stable diabetes medication during the study unless medically indicated
   6. Positive urine toxic screen for any drugs of abuse other than marijuana at Screening Visit
   7. HbA1c ≥ 10.0% at either the screening or randomization visit

2. Psychiatric factors:

   1. Current major depressive episode, by report and as indicated by the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR).
   2. Subjects with active or unstable major psychiatric disorder, who, in the investigator's judgement, require further treatment.
   3. Current alcohol/substance use disorder

3. Medical factors:

   1. Renal or hepatic disease judged to interfere with drug metabolism and excretion
   2. Pregnant or breastfeeding
   3. Malignancy within past 2 years
   4. Surgery within past 3 months
   5. 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
   6. Medical instability considered to interfere with study procedures
   7. Concomitant medications with drug interaction or co-administration concerns
   8. Contraindications or allergic responses to suvorexant
   9. History of being treated with suvorexant

4. Lifestyle and other factors:

   1. Travel across two time-zones during the week prior to enrollment
   2. Greater than 6 cups of coffee per day

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / 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	Other: Placebo; Matching placebo capsules; Drug: Suvorexant; 10-mg or 20-mg Suvorexant capsules; Other Names: Belsomra
Placebo Comparator: Placebo Non-responders Re-randomized to Placebo	Other: Placebo; Matching placebo capsules

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: John W Winkelman, MD/PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): November 3, 2021
• Study Completion (Actual): November 3, 2021

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Sleep Disorders, Intrinsic; Neurologic Manifestations; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Inflammation; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Dyssomnias; Parasomnias; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: 2019P000076

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No