Blocking orexin receptors to reduce alcohol use and stress-related drinking

Orexin Receptor Antagonism for the Treatment of Alcohol Use Disorder and Stress-Related Drinking

This trial tests whether taking suvorexant at bedtime helps adults with moderate to severe alcohol use disorder drink less and have smaller stress reactions.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Ohio State University (Academic / other)
• Locations: 1 site (Columbus, Ohio)
• Trial ID: NCT07214207 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled Phase 2 trial gives adults with moderate to severe alcohol use disorder either 10 mg suvorexant or a matching placebo each night for eight weeks. Participants come to the lab at baseline, four weeks, and eight weeks for a psychophysiological stress paradigm including electromyography (EMG) and provide daily smartphone reports on medication use, side effects, sleep, alcohol use, and mood. The study compares drinking and stress reactivity between the suvorexant and placebo groups and aims to identify EMG or other markers that predict who responds to suvorexant. Eligibility is limited to medically and neurologically stable, treatment-seeking adults aged 18–65 who meet criteria for moderate to severe alcohol use disorder and engage in heavy drinking.

Who should consider this trial

Good fit: Ideal candidates are treatment-seeking adults aged 18–65 with moderate to severe alcohol use disorder who engage in heavy drinking and are generally medically and neurologically healthy.

Not a fit: People with serious medical, neurologic, or sleep disorders (e.g., narcolepsy, severe obstructive sleep apnea), significant hepatic or respiratory impairment, current psychotic or bipolar disorders, or current substance use disorders other than alcohol or mild cannabis are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, suvorexant could reduce alcohol consumption and decrease stress-related drinking in people with moderate to severe alcohol use disorder.

How similar studies have performed: Preclinical work and limited clinical data on orexin antagonists suggest potential to reduce alcohol-seeking and stress-related drinking, but suvorexant's direct effectiveness for AUD remains only modestly tested in humans.

Eligibility criteria

Inclusion Criteria:

* Generally medically and neurologically healthy;
* Age 18 to 65 at the time of consent;
* Willing and able to give informed consent;
* Current DSM-5 diagnosis of moderate to severe alcohol use disorder;
* Engages in heavy alcohol use defined as drinking ≥14 standard drinks per week if male, and ≥7 standard drinks per week if female;
* Self-reported treatment-seeking for alcohol use disorder

Exclusion Criteria:

* Clinically significant medical or neurologic condition or neurocognitive dysfunction that would affect function, and/or task performance, and/or interfere with the study protocol, and/or be contraindicated for suvorexant including sleep disorders (e.g., narcolepsy; severe obstructive sleep apnea), hepatic impairment, compromised respiratory function, renal impairment, and endocrine disorders;
* Lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder;
* Current substance use disorder (SUD) other than alcohol or mild cannabis use disorder;
* Currently pregnant (positive pregnancy test), lactating, or not agreeing to use birth control methods during the duration of the trial (women);
* Any use of medications for alcohol use disorder or any psychotropic medications (e.g., psychostimulants and benzodiazepines, some antidepressants);
* Current antihistamines use or medication use that may increase risk including, prescribed, over-the-counter, and herbal preparations, as determined by the study physician;
* Current use of strong or moderate inhibitors of CYP3A liver enzymes;
* Current use of strong CYP3A inducers;
* Current use of digoxin;
* Liver function tests more than 3 times the upper limit of normal or elevated bilirubin;
* Engages in night shift work;
* Smoke 10 or more cigarettes (or electronic equivalent) per day and are thus susceptible to acute nicotine withdrawal during lab visits;
* Obesity as defined by a body-mass index (BMI) equal or greater than 30, as calculated from weight and height self-report;
* Clinically significant alcohol withdrawal symptoms the day of the lab sessions, defined as a score \>10 on the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar);
* Unwilling/unable to sign the informed consent document;
* Under 18 years old or over 65 years old at the time of enrollment;
* Have attempted suicide in the past 3 years and/or have current suicidal ideation determined as greater than moderate via the Columbia Suicide Severity Rating Scale (C-SSRS)

Where this trial is running

Columbus, Ohio

• Ohio State University — Columbus, Ohio, United States (Recruiting)

Study contacts

• Study coordinator: Stephanie Gorka

Conditions Alcohol Use Disorder; suvorexant; alcohol use disorder; electromyography