Dual-Orexin Antagonism As a Mechanism for Improving Sleep and Drug Abstinence in Opioid Use Disorder

Wayne State University

Status and phase: Terminated; Phase 2

Conditions: Opioid-use Disorder; Sleep

Treatments: Drug: Suvorexant Placebo; Drug: Suvorexant

Study type: Interventional

Funder types: Other

Identifiers

NCT04262193

DORA, Sleep and Opioid Use

Details and patient eligibility

About

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.

Full 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).

Enrollment: 37 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

37 participants in 2 patient groups, including a placebo group

Suvorexant placebo

Placebo Comparator group

Description:

Placebo (inert) tablet

Treatment:

Drug: Suvorexant Placebo

Suvorexant 20mg

Experimental group

Description:

Suvorexant 20mg tablet

Treatment:

Drug: Suvorexant