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

• ClinicalTrials.gov Identifier: NCT03818581
• Recruitment Status: Active, not recruiting
• First Posted: January 28, 2019
• Last Update Posted: September 2, 2021
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): John Winkelman, MD, PhD, Massachusetts General Hospital

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 (Clinical Trial)
• 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.
• 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: March 15, 2019
• Estimated Primary Completion Date: September 15, 2021
• Estimated Study Completion Date: September 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment Group	Drug: Suvorexant; 10-mg or 20-mg Suvorexant capsules; Other Name: 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 Name: 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 :

1. Subjective Total Sleep Time [ Time Frame: 2 weeks ]
   Total sleep time as reported on daily sleep diaries

Secondary Outcome Measures :

1. Subjective Wake After Sleep Onset [ Time Frame: 2 weeks ]
   Total time awake after sleep onset as reported on daily sleep diaries
2. Insomnia Severity Index [ Time Frame: 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

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

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 25-75 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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

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

More Information

• Responsible Party: John Winkelman, MD, PhD, Chief, Sleep Disorders Clinical Research Program, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03818581
• Other Study ID Numbers: 2019P000076
• First Posted: January 28, 2019
• Last Update Posted: September 2, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

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