Medical Management of Sleep Disturbance During Opioid Tapering

Study Overview
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Brief Summary
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This study will evaluate whether a dual orexin-receptor antagonist approved by the FDA for sleep disturbance, suvorexant (SUVO; Belsomra), will increase total sleep time in patients with opioid use disorder (OUD) undergoing supervised withdrawal. This study is designed as a dose-finding study of SUVO compared to placebo. Briefly, OUD patients seeking supervised withdrawal will be admitted into a clinical research unit and stabilized onto buprenorphine for three days before being randomly assigned to study condition. All participants will then undergo a routine four-day buprenorphine taper, followed by a four-day post-taper phase. Participants will be randomized to receive either placebo, Low Dose SUVO, or High Dose SUVO and the investigators hypothesize that one or both doses of SUVO will improve total sleep time relative to placebo. Patients will attend a single follow-up session, 5-10 days following discharge.

Official Title
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Medical Management of Sleep Disturbance During Opioid Tapering

Conditions
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Opioid Dependence, Opioid Withdrawal, Sleep Disturbance

Intervention / Treatment
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* Drug: Placebo oral capsule
* Drug: Low Dose Suvorexant
* Drug: High Dose Suvorexant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years old and above Meets Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for OUD with evidence of physical dependence on opioids, and seeking treatment to stop using illicit opioids. Provides a urine sample that tests positive for opioids. Willing to comply with the study protocol. Have no clinically significant chronic medical or surgical disorders or conditions that are judged by the investigators to prevent participation. Exclusion Criteria: Seeking or currently enrolled in methadone or buprenorphine maintenance treatment for OUD Pregnant or breast feeding Have evidence of physical dependence on alcohol or benzodiazepines that requires medical detoxification Have a known allergy to the study medications Past 30-day prescribed use of suvorexant or benzodiazepines for the indication of insomnia Current use of a Selective Serotonin Reuptake Inhibitor (SSRI) or Monoamine oxidase (MAO) inhibitor for depression or insomnia, or other medications that are contraindicated with suvorexant Current narcolepsy, restless leg syndrome or sleep paralysis High risk for current sleep apnea Current major depressive disorder Past year suicidal behavior Severe hepatic or renal impairment Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3x ULN Total bilirubin >2x Upper Limit of Normal (ULN) Creatinine >1.5x ULN Have circumstances that would interfere with study participation (e.g., impending jail)

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo sleep medication (Placebo oral capsule) | Drug: Placebo oral capsule<br>* Placebo Sleep Medication<br>|
| Active Comparator: Low Dose Suvorexant<br>Low dose sleep medication | Drug: Low Dose Suvorexant<br>* Low Dose Suvorexant<br>|
| Active Comparator: High Dose Suvorexant<br>High dose sleep medication | Drug: High Dose Suvorexant<br>* High Dose Suvorexant<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abuse Liability as Assessed by Visual Analogue Scale | Area-under-the-curve of self-reported feelings of drug High on the morning after study drug administration, measured each morning on a 0-100 point visual analogue scale of the question Last night, did you feel HIGH?. A score of 0 indicates no abuse liability and a score of 100 indicates extreme abuse liability. This will be assessed over four nights during an opioid taper. | 4 nights | 
| Total Sleep Time During Buprenorphine Taper | Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy. | Four nights during a buprenorphine taper | 
| Total Sleep Time During Post-taper | Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy. | Four nights following buprenorphine discontinuation | 
| Subjective Opiate Withdrawal Scale During Buprenorphine Taper | Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal). | Three days during a buprenorphine taper | 
| Subjective Opiate Withdrawal Scale During Post-taper | Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal). | Three days following buprenorphine discontinuation |