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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrew S Huhn, PhD; Phone Number: 410-550-1971; Email: ahuhn1@jhu.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Behavioral Pharmacology Research Unit at the Johns Hopkins Bayview Medical Center
      • Contact: Andrew S Huhn, PhD; Phone Number: 410-550-1971; Email: ahuhn1@jhu.edu
    • Baltimore, Maryland, United States, 21218
      • Recruiting
      • Man Alive Inc., Lane Treatment Center
      • Contact: Karen Reese, M.A.; Phone Number: 300 410-837-4292; Email: kreese@manaliveinc.org
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Addiction Treatment Services at Johns Hopkins Bayview Medical Center
      • Contact: Andrew S Huhn, PhD; Phone Number: 410-550-1971; Email: ahuhn1@jhu.edu
    • Bel Air, Maryland, United States, 21014
      • Recruiting
      • Ashley Addiction Treatment
      • Contact: Andrew S Huhn, PhD; Phone Number: 410-550-1971; Email: ahuhn1@jhu.edu
    • Elkton, Maryland, United States, 21921
      • Recruiting
      • Ashley Addiction Treatment
      • Contact: Andrew S Huhn, PhD; Phone Number: 410-550-1971; Email: ahuhn1@jhu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo sleep medication (2 placebo oral capsules)	Drug: Placebos; Weight and color matched placebo
Active Comparator: Suvorexant; Sleep medication (20mg suvorexant; 2 10mg capsules; patients can self-titrate to 1 10mg capsule)	Drug: Suvorexant; Dual orexin receptor antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Andrew S Huhn, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2020
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 27, 2020

Study Record Updates

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

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Nervous System Diseases; Sleep Wake Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Dyssomnias; Parasomnias; 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: IRB00223942; U01HL150835 (U.S. NIH Grant/Contract)

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