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

Johns Hopkins University

Status and phase: Completed; Phase 2

Conditions: Opioid-use Disorder; Sleep Disturbance

Treatments: Drug: Suvorexant; Drug: Placebos

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04287062

IRB00223942

U01HL150835 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 138 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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138 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo sleep medication (2 placebo oral capsules)

Treatment:

Drug: Placebos

Suvorexant

Active Comparator group

Description:

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

Treatment:

Drug: Suvorexant