Suvorexant as an Adjunct to Buprenorphine in Persons Who Use Fentanyl

Study Overview
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Brief Summary
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This is a 4-week, randomized-controlled trial of suvorexant vs placebo in persons with opioid use disorder who have recent fentanyl exposure. Participants will first undergo a 5-day residential phase wherein participants are stabilized on sublingual buprenorphine/naloxone, followed by a 3-week outpatient phase wherein participants are maintained on sublingual buprenorphine/naloxone and transitioned to extended-release buprenorphine).

Detailed Description
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This study will enroll persons with opioid use disorder (N=120) who have recent fentanyl exposure (as assessed via urinalysis testing). Participants will be randomized to receive suvorexant or placebo for the duration of the study enrollment, which will serve as the between-groups experimental comparison. The study will consist of a brief (5 day) residential phase and 3-week outpatient phase. During the residential phase, all participants will be briefly maintained on a short acting opioid prior to induction onto sublingual (SL) buprenorphine (using either the buprenorphine or buprenorphine/naloxone product). At the end of the 5-day residential period, participants will be discharged to complete the  3-week outpatient phase. During the outpatient period all participants will be maintained on SL buprenorphine/naloxone and continue to receive suvorexant or placebo, and at the end of the study participants will receive an injection of XR-buprenorphine (Sublocade). All buprenorphine procedures will be open label and will follow standard-of-care practices. Study medication during the outpatient period will be managed using an automated pill dispenser. Data collection will consist of forehead-based EEG monitoring, wrist-worn actigraphy/photoplethysmography, and questionnaires delivered during study visits or via cell-phone based ecological momentary assessments.

Official Title
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Suvorexant as an Adjunct to Buprenorphine Induction and Maintenance in Persons Who Use Fentanyl

Conditions
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Suvorexant, Placebo, Opioid Use Disorder

Intervention / Treatment
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* Drug: Suvorexant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65 Meets DSM-5 criteria for opioid use disorder (OUD) with evidence of physical dependence on opioids Provides a urine sample that tests positive for fentanyl and/or fentanyl analogues Interest in being maintained on buprenorphine for OUD Plans to reside in current area for study period Achieving a study maintenance dose of >=8mg sublingual buprenorphine/naloxone Willing to comply with study protocol Have no clinically significant chronic medical or surgical disorders or conditions that are judged by the investigators to prevent participation Exclusion Criteria: Medically contraindicated for buprenorphine, extended-release (XR)-buprenorphine (Sublocade), or suvorexant (as per medication labels) Pregnant or breast feeding Severe Diagnostic and Statistical Manual (DSM)-5 alcohol, benzodiazepine, or stimulant use disorder or evidence of alcohol/benzodiazepine physical dependence Have a known allergy to the study medications Past 30-day prescribed use of suvorexant for the indication of insomnia Current benzodiazepine or other prescribed medication for the indication of insomnia Urine sample testing positive for benzodiazepine at screening and admission to residential treatment Current narcolepsy, restless leg syndrome or sleep paralysis High risk for current sleep apnea Current (past 30-day) suicidal behaviors Severe hepatic or renal impairment aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3x upper limit of normal (ULN) Total bilirubin >2x ULN Creatinine >1.5x ULN Past year clinically-significant psychiatric condition judged to interfere with study participation Lack of access to stable housing (necessary for electronic pill dispenser charging) Have circumstances that would interfere with study participation (e.g., impending jail)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Suvorexant<br>Nightly dosing of suvorexant | Drug: Suvorexant<br>* Encapsulated suvorexant (matched for color, weight, and size)<br>|
| Placebo Comparator: Placebo<br>Nightly dosing of placebo | Drug: Placebo<br>* Encapsulated placebo (matched for color, weight, and size)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Sleep Time | Duration of nightly total sleep time in minutes, as measured by electroencephalography (EEG) and supplemented by actigraphy/photoplethysmography (e.g., if EEG malfunctions). | 3 nights during the initial residential phase and 1 night at the end of outpatient treatment | 
| Buprenorphine compliance as assessed by the number of study days complying with buprenorphine treatment | Buprenorphine compliance will be assessed by the number of study days complying with buprenorphine treatment. | 25 days across residential and outpatient treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid use disorder, Insomnia, Suvorexant, Fentanyl, Buprenorphine