Clinical trial NCT04262193: Dual-Orexin Antagonism As a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder
Official title: Dual-Orexin Antagonism As a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Opioid-use Disorder
Sleep
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: Henry Ford Health System
name: Ascension Brighton Center for Recovery
First posted: 2020-02-10
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to one of the 2 parallel groups for the duration of the study.
Primary purpose: BASIC_SCIENCE

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. 120 participants with opioid use disorder (OUD) will complete this intent-to-treat study.

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 (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 include current medication for treating OUD, as well as treatment site, as stratification factors in the group allocation. Using power and sample size calculations, we estimate that 120 participants will suffice to test our hypotheses.

The study aims to test three co-primary hypotheses:

Hypothesis 1: Relative to placebo, suvorexant (20 mg/day) will significantly increase percentage opioid abstinence during outpatient weeks 1-13.

Hypothesis 2: Relative to placebo, suvorexant will improve sleep efficiency.

Hypothesis 3: Higher inpatient sleep efficiency will be associated with increased outpatient opioid abstinence (independent of experimental group assignment).

Eligibility criteria: Inclusion Criteria:

* Age 18-70 years old
* Males and non-pregnant females who agree to medically accepted birth control for the duration of the study
* Meet DSM-5 criteria for opioid use disorder (any severity level) alone or comorbid with stable medical diseases (except for certain medications \[see below\])

Exclusion Criteria:

* Body mass index \>38
* Acute/unstable illness: conditions making it unsafe for participation, conditions with potential to disturb sleep (i.e. acute pain, respiratory infection)
* Chronic illnesses; renal failure, liver disease, seizures, and dementing illnesses
* Current psychiatric disease: psychosis, bipolar disorder, PTSD
* Smoking during the night (11pm-7am). Nicotine replacement therapy is allowed
* 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
* 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
* Night-shift work, which would alter circadian rhythm and be a confound in this trial.

Primary outcomes:
measure: Opioid abstinence
timeFrame: up to 13 weeks
measure: Sleep efficiency
timeFrame: Sleep efficiency is measured on the evening of the first medication dose
Secondary outcomes:
measure: Daily sleep questionnaire
timeFrame: Change in sleep quality scores from inpatient stay to outpatient weeks 2, 6 and 10
measure: Actigraphic assessment of sleep
timeFrame: Change in total activity counts across outpatient weeks 2, 6 and 10
measure: Weekly sleep questionnaire
timeFrame: Change in sleep quality scores across outpatient weeks 1, 4, 8 and 12
measure: Timeline followback interview assessment of substance use
timeFrame: Once weekly (in conjunction with urine drug screen) on outpatient weeks 1 through 13
measure: Urinary cortisol
timeFrame: 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
measure: Urinary melatonin
timeFrame: 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
measure: Clinical Global Impression (CGI)
timeFrame: Change in CGI subscale scores across outpatient weeks 4, 8, and 12
measure: Short Form-36 v2 Health Survey
timeFrame: Change in overall health total score across outpatient weeks 4, 8, and 12
measure: Medication satisfaction
timeFrame: Change in medication satisfaction score across outpatient weeks 4, 8, and 12
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
Study officials:
affiliation: Wayne State University
name: Mark K Greenwald, PhD
role: PRINCIPAL_INVESTIGATOR
References: