Examining the Role of the Orexin System in Sleep and Stress in Persons With Opioid Use Disorder

NCT04287062 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: IRB00223942U01HL150835
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 5

Brief Summary

This study is designed to elucidate the role of the orexin neurotransmitter system in sleep disturbance and circadian rhythms of stress that might in turn influence relapse behaviors in persons on medication-assisted treatments (MAT) who are in early recovery from opioid use disorder (OUD). Briefly, the study will enroll recently abstinent OUD patients (N=200) maintained on either extended-release naltrexone (XR-NTX), buprenorphine, or methadone. Within each MAT group, participants will be randomized to either suvorexant or placebo. The study is expected to have a 20% treatment attrition rate which will result in N=160 completers in the entire study. Patients will be recruited from and treated at Ashley Addiction Treatment, Addiction Treatment Services at Johns Hopkins Bayview Medical Center, Man Alive, or community providers.

Conditions

Sleep Disturbance; Opioid-use Disorder

Outcome Measures

Primary Outcomes (3)

• Total Sleep Time

  Mean total number of minutes slept per night as measured by actigraphy and self-reported sleep diary. Mean total sleep time will be collected over a seven-night period in weeks 1, 4, and 8 of the trial.

  21 nights

• Total Wake Time After Sleep Onset

  Mean total number of minutes awake between initial sleep onset and final morning awakening, measured by actigraphy and self-reported sleep diary. Mean wake after sleep onset will be collected over a seven-night period in weeks 1, 4, and 8 of the trial.

  21 nights

• Change in Perceived Stress Scale 4 (PSS-4) score

  Mean daily scores on the PSS-4 (a four item scale self-reported scale than measures stress using a 0-4 Likert scale; total range of PSS-4 scores is 0-16; lower scores indicate lower daily stress relative to higher scores, which indicate higher daily stress). Mean PSS-4 scores will be collected over a seven-day period in weeks 1, 4, and 8 of the trial.

  21 days (collected over a seven-day period in weeks 1, 4, and 8 of the trial)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo sleep medication (2 placebo oral capsules)

Drug: Placebos

Suvorexant

ACTIVE COMPARATOR

Sleep medication (20mg suvorexant; 2 10mg capsules; patients can self-titrate to 1 10mg capsule)

Drug: Suvorexant

Interventions

Suvorexant DRUG

Dual orexin receptor antagonist

Suvorexant

Placebos DRUG

Weight and color matched placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Gender Eligibility Details: Self-reported male or female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 21-65, inclusive.
• Past 30-day sleep disturbance as evidenced by a Pittsburgh Sleep Quality Index Total Score \>5.
• Enrolled in either outpatient methadone-maintenance, buprenorphine-maintenance, or XR-NTX treatment for OUD.
• Willingness to be maintained on a protocolized dose starting between 60-130mg methadone or 380mg XR-NTX for the duration of the study.
• At least two weeks of continuous abstinence from illicit opioids as evidenced by self-report and urine drug screens collected as part of routine care.
• Willing to comply with the study protocol, which will include weekly study visits, daily actigraphy and ecological momentary assessments.
• Use of birth control throughout study.
• Have no clinically significant chronic medical disorders or conditions that are judged by the investigators to prevent participation.

You may not qualify if:

• Serious mental illnesses that are unstable and could affect study participation (thought disorders, hallucinations, delusions, thoughts of harm to self/others).
• Current moderate to severe substance use disorder other than OUD.
• Current illicit stimulant use, including cocaine and methamphetamine.
• Pregnant or breast feeding.
• Have a known allergy to the study medications.
• Past 30-day prescribed use of suvorexant.
• Current use of a benzodiazepine or other schedule IV medication for insomnia.
• Use of Cytochrome P450 3A inhibitors.
• Current narcolepsy, sleep paralysis, or restless leg syndrome as assessed by medical history
• Apnea-hypopnea index \> 30.
• Use of glucocorticoid medications and any medication that would alter the hypothalamic-pituitary-adrenal axis.
• Past 30-day suicidal behavior as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS).
• Have circumstances that would interfere with study participation (e.g., impending jail; severe clinical issues).

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (5)

Man Alive Inc., Lane Treatment Center

Baltimore, Maryland, 21218, United States

Location

Addiction Treatment Services at Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Behavioral Pharmacology Research Unit at the Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Ashley Addiction Treatment

Bel Air, Maryland, 21014, United States

Location

Ashley Addiction Treatment

Elkton, Maryland, 21921, United States

Location

MeSH Terms

Conditions

Parasomnias; Opioid-Related Disorders

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Andrew S Huhn, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: February 27, 2020
• Study Start: November 20, 2020
• Primary Completion: August 15, 2025
• Study Completion: August 15, 2025
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)