Dual-Orexin Antagonism as a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder
Study Details
Study Description
Brief Summary
Summary of Study Protocol. This project is designed to test neurobehavioral mechanisms underlying effects of the dual orexin-1/2 receptor antagonist suvorexant on sleep efficiency and opioid abstinence, and whether these outcomes are independent of one another. This will be the first study to investigate whether suvorexant improves outpatient opioid abstinence and sleep efficiency; and whether improving sleep mediates the improved opioid abstinence outcome. 180 participants with opioid use disorder (OUD) who have just completed detoxification will complete this intent-to-treat study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Study Design. Using a placebo-controlled, parallel-group, randomized clinical trial design, we will prospectively evaluate whether nightly treatment with the orexin-1/2 receptor antagonist suvorexant (10 or 20 mg/day PO), relative to placebo, can increase outpatient opioid abstinence and improve sleep efficiency (sleep time per time-in-bed) as a mediator/moderator among patients with OUD. We have included current major depression and current alcohol use disorder severity as stratification factors in the group allocation. Using power and sample size calculations, we estimate that 60 participants in each study arm will suffice to test our hypotheses. We anticipate enrolling 210 participants to obtain the 180 completers (60 participants in each of the 3 treatment arms).
The study aims to test three co-primary hypotheses:
Hypothesis 1: Relative to placebo, at least one of the two suvorexant doses (10 or 20 mg/day) will significantly increase percentage opioid abstinence during outpatient weeks 1-13.
Hypothesis 2: Relative to placebo (i.e. expected sleep loss related to opioid detoxification), at least one of the two suvorexant doses will improve sleep efficiency during the inpatient stay.
Hypothesis 3: Higher inpatient sleep efficiency will be associated with increased outpatient opioid abstinence (independent of experimental group assignment).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Suvorexant placebo Placebo (inert) tablet |
Drug: Suvorexant Placebo
Suvorexant Placebo
|
| Experimental: Suvorexant 10mg Suvorexant 10mg tablet |
Drug: Suvorexant
In each group, the participant will take 1 tablet (placebo, 10mg or 20mg) 30 minutes before bedtime.
Other Names:
|
| Experimental: Suvorexant 20mg Suvorexant 20mg tablet |
Drug: Suvorexant
In each group, the participant will take 1 tablet (placebo, 10mg or 20mg) 30 minutes before bedtime.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Opioid abstinence [up to 13 weeks]
Percentage of opioid-free urine drug screens (UDS)
- Sleep efficiency [Sleep efficiency is measured on the night before discharge from the inpatient unit]
Sleep efficiency equals sleep time (determined by standardized scoring of electroencephalogram recordings) divided by time in bed
Secondary Outcome Measures
- Daily sleep questionnaire [Change in sleep quality scores from inpatient stay to outpatient weeks 2, 6 and 10]
Morning (post-awakening) assessment of sleep quality
- Actigraphic assessment of sleep [Change in total activity counts across outpatient weeks 2, 6 and 10]
Actigraphic assessment of motion (activity counts), measured with Actiwatch and scoring software; motion is absent during sleep.
- Weekly sleep questionnaire [Change in sleep quality scores across outpatient weeks 1, 4, 8 and 12]
Retrospective (past-week) self-report of sleep quality on each of 4 outpatient weeks
- Timeline followback interview assessment of substance use [Once weekly (in conjunction with urine drug screen) on outpatient weeks 1 through 13]
Percentage of outpatient weeks with substance use (opioids, methadone, buprenorphine, cocaine metabolites, benzodiazepines, barbiturates, cannabinoids, amphetamines)
- Urinary cortisol [Measured at 11pm on nights 4, 6, 8 (coordinated with sleep efficiency and melatonin assessments) and the following day (7am and 3pm on days 5, 7, 9) on the inpatient unit]
Change in cortisol levels in picogram per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm
- Urinary melatonin [Measured at 11pm on nights 4, 6, 8 (coordinated with sleep efficiency and cortisol assessments) and the following day (7am and 3pm on days 5, 7, 9) on the inpatient unit]
Change in melatonin levels in picograms per milliliter (pg/ml) across 24 hour interval used to measure circadian rhythm
- Clinical Global Impression (CGI) [Change in CGI subscale scores across outpatient weeks 4, 8, and 12]
CGI subscale scores for improvement and severity. Each subscale is scored on a 1-7 scale. Higher scores indicate worse (more severe) outcomes.
- Short Form-36 v2 Health Survey [Change in overall health total score across outpatient weeks 4, 8, and 12]
Overall health assessment. The 36 items are grouped into 8 dimensions: physical functioning, physical and emotional limitations, social functioning, bodily pain, general and mental health. Each scale is directly transformed into a 0-100 scale. Lower scores on each scale indicate greater disability.
- Medication satisfaction [Change in medication satisfaction score across outpatient weeks 4, 8, and 12]
Assessment of satisfaction with assigned medication condition, on 1-7 Likert scale. Higher scores indicate greater medication satisfaction.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 18-70 years old
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Males and non-pregnant females who agree to medically accepted birth control for the duration of the study
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Meet DSM-5 criteria for opioid use disorder (any severity level) alone or comorbid with stable medical diseases (except for certain medications [see below])
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Must complete opioid detoxification (days 1-4 on the inpatient unit)
Exclusion Criteria:
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Body mass index >38
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Acute/unstable illness: conditions making it unsafe for participation, conditions with potential to disturb sleep (i.e. acute pain, respiratory infection)
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Chronic illnesses; renal failure, liver disease, seizures, and dementing illnesses
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Current psychiatric disease: psychosis, bipolar disorder, PTSD
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Smoking during the night (11pm-7am). Nicotine replacement therapy is allowed
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Medications including anxiolytics, hypnotics (both prescription and OTC), sedating antidepressants, anticonvulsants, sedating H1 antihistamines (non-sedating second generation H4 antihistamines are allowed), systemic steroids, respiratory stimulants and decongestants, prescription and OTC stimulants, prescription and OTC diet aids, herbal preparations, and narcotic analgesics. All medications and doses will be documented
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Sleep-disordered breathing and periodic leg movements (PLMs) defined as ≥ 10 apnea-hypopneas or PLM events related to EEG arousal per hour of sleep time, or any other primary sleep (e.g. narcolepsy, restless legs syndrome) or circadian disorder
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Night-shift work, which would alter circadian rhythm and be a confound in this trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Wayne State University | Detroit | Michigan | United States | 48202 |
Sponsors and Collaborators
- Wayne State University
- Henry Ford Health System
Investigators
- Principal Investigator: Mark K Greenwald, PhD, Wayne State University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- OX-Sleep-OUD