Dual-Orexin Antagonism as a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder

Summary of Study Protocol. This project is designed to test neurobehavioral mechanisms underlying effects of the dual orexin-1/2 receptor antagonist suvorexant on sleep efficiency and opioid abstinence, and whether these outcomes are independent of one another. This will be the first study to investigate whether suvorexant improves outpatient opioid abstinence and sleep efficiency; and whether improving sleep mediates the improved opioid abstinence outcome. 120 participants with opioid use disorder (OUD) will complete this intent-to-treat study.

Study Overview

• Status: Recruiting
• Conditions: Sleep; Opioid-use Disorder
• Intervention / Treatment: Drug: Suvorexant Placebo; Drug: Suvorexant

Detailed Description

Study Design. Using a placebo-controlled, parallel-group, randomized clinical trial design, we will prospectively evaluate whether nightly treatment with the orexin-1/2 receptor antagonist suvorexant (20 mg/day PO), relative to placebo, can increase outpatient opioid abstinence and improve sleep efficiency (sleep time per time-in-bed) as a mediator/moderator among patients with OUD. We include current medication for treating OUD, as well as treatment site, as stratification factors in the group allocation. Using power and sample size calculations, we estimate that 120 participants will suffice to test our hypotheses.

The study aims to test three co-primary hypotheses:

Hypothesis 1: Relative to placebo, suvorexant (20 mg/day) will significantly increase percentage opioid abstinence during outpatient weeks 1-13.

Hypothesis 2: Relative to placebo, suvorexant will improve sleep efficiency.

Hypothesis 3: Higher inpatient sleep efficiency will be associated with increased outpatient opioid abstinence (independent of experimental group assignment).

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mark K Greenwald, PhD; Phone Number: 313-993-3965; Email: mgreen@med.wayne.edu

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Wayne State University
      • Contact: Mark Greenwald, PhD; Phone Number: 313-993-3965; Email: mgreen@med.wayne.edu
      • Principal Investigator: Mark Greenwald, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-70 years old
• Males and non-pregnant females who agree to medically accepted birth control for the duration of the study
• Meet DSM-5 criteria for opioid use disorder (any severity level) alone or comorbid with stable medical diseases (except for certain medications [see below])

Exclusion Criteria:

• Body mass index >38
• Acute/unstable illness: conditions making it unsafe for participation, conditions with potential to disturb sleep (i.e. acute pain, respiratory infection)
• Chronic illnesses; renal failure, liver disease, seizures, and dementing illnesses
• Current psychiatric disease: psychosis, bipolar disorder, PTSD
• Smoking during the night (11pm-7am). Nicotine replacement therapy is allowed
• Medications including anxiolytics, hypnotics (both prescription and OTC), sedating antidepressants, anticonvulsants, sedating H1 antihistamines (non-sedating second generation H4 antihistamines are allowed), systemic steroids, respiratory stimulants and decongestants, prescription and OTC stimulants, prescription and OTC diet aids, herbal preparations, and narcotic analgesics. All medications and doses will be documented
• Sleep-disordered breathing and periodic leg movements (PLMs) defined as ≥ 10 apnea-hypopneas or PLM events related to EEG arousal per hour of sleep time, or any other primary sleep (e.g. narcolepsy, restless legs syndrome) or circadian disorder
• Night-shift work, which would alter circadian rhythm and be a confound in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Suvorexant placebo; Placebo (inert) tablet	Drug: Suvorexant Placebo; Suvorexant Placebo
Experimental: Suvorexant 20mg; Suvorexant 20mg tablet	Drug: Suvorexant; In each group, the participant will take 1 tablet (placebo or 20mg) 30 minutes before bedtime.; Other Names: Belsomra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid abstinence	Percentage of opioid-free urine drug screens (UDS)	up to 13 weeks
Sleep efficiency	Sleep efficiency equals sleep time (determined by standardized scoring of electroencephalogram recordings) divided by time in bed	Sleep efficiency is measured on the evening of the first medication dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily sleep questionnaire	Morning (post-awakening) assessment of sleep quality	Change in sleep quality scores from inpatient stay to outpatient weeks 2, 6 and 10
Actigraphic assessment of sleep	Actigraphic assessment of motion (activity counts), measured with Actiwatch and scoring software; motion is absent during sleep.	Change in total activity counts across outpatient weeks 2, 6 and 10
Weekly sleep questionnaire	Retrospective (past-week) self-report of sleep quality on each of 4 outpatient weeks	Change in sleep quality scores across outpatient weeks 1, 4, 8 and 12
Timeline followback interview assessment of substance use	Percentage of outpatient weeks with substance use (opioids, methadone, buprenorphine, cocaine metabolites, benzodiazepines, barbiturates, cannabinoids, amphetamines)	Once weekly (in conjunction with urine drug screen) on outpatient weeks 1 through 13
Urinary cortisol	Change in cortisol levels in picogram per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm	Measured at 11pm on nights 4, 6, 8 (coordinated with sleep efficiency and melatonin assessments) and the following day (7am and 3pm on days 5, 7, 9) on the inpatient unit
Urinary melatonin	Change in melatonin levels in picograms per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm	Measured at 11pm on nights 4, 6, 8 (coordinated with sleep efficiency and cortisol assessments) and the following day (7am and 3pm on days 5, 7, 9) on the inpatient unit
Clinical Global Impression (CGI)	CGI subscale scores for improvement and severity. Each subscale is scored on a 1-7 scale. Higher scores indicate worse (more severe) outcomes.	Change in CGI subscale scores across outpatient weeks 4, 8, and 12
Short Form-36 v2 Health Survey	Overall health assessment. The 36 items are grouped into 8 dimensions: physical functioning, physical and emotional limitations, social functioning, bodily pain, general and mental health. Each scale is directly transformed into a 0-100 scale. Lower scores on each scale indicate greater disability.	Change in overall health total score across outpatient weeks 4, 8, and 12
Medication satisfaction	Assessment of satisfaction with assigned medication condition, on 1-7 Likert scale. Higher scores indicate greater medication satisfaction.	Change in medication satisfaction score across outpatient weeks 4, 8, and 12

Collaborators and Investigators

• Sponsor: Wayne State University
• Collaborators: Henry Ford Health System; Ascension Brighton Center for Recovery
• Investigators: Principal Investigator: Mark K Greenwald, PhD, Wayne State University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: February 7, 2020
• First Posted (Actual): February 10, 2020

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Opioid-Related Disorders; 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: OX-Sleep-OUD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This is under development, in collaboration with NIH officials. This project is funded under the NIH HEAL Initiative, which will require data sharing; details are being determined.
• IPD Sharing Time Frame: Electronic copies of publications will be deposited within 4 weeks of acceptance. Underlying primary data will be made publicly available as soon as possible (time frame to be determined).
• IPD Sharing Access Criteria: NIH will be managing sharing of data on a common web site (to be determined).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

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.: Yes