Early Phase 1
N=64
Orexin Receptor Antagonists as Modulators of Threat Sensitivity in Individuals With Alcohol Use Disorder
Alcohol Use Disorder
Bottom Line
View on ClinicalTrials.gov: NCT05656534 ↗Enrolled (actual)
64
Serious AEs
0.0%
Results posted
Oct 2025
Primary outcome: Primary: Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant — 0.01; .24; 0.01; -0.18 Standardized residual scores — p=.19
Study Design & Population
- Study type
- Interventional
- Phase
- Early Phase 1
- Interventions
- Suvorexant (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ohio State University
- Primary completion
- Aug 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Startle Eyeblink Electromyographic (EMG) Response to Stress With an Acute Dose of Suvorexant |
0.01; .24; 0.01; -0.18 | .19 |
| PRIMARY Startle Eyeblink Electromyographic (EMG) Response to Stress With Daily Use of Suvorexant. |
-0.13; 0.28; 0.08; -0.23 | 0.03 sig |
| PRIMARY Percentage of Heavy Drinking Days During Daily Use of Suvorexant. |
27.7; 29.5; 31.2; 29.5; 27.2; 24.4 | .01 sig |
| SECONDARY Changes in Neural Activation During Unpredictable Stress Anticipation Following Daily Use of Suvorexant. |
0.330; 0.652; 0.482; 0.226 | <.05 sig |
Summary
The goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (AUD). The main questions it aims to answer are:
* Does an acute dose of suvorexant (SUV) and/or daily use of SUV modify brain-behavior targets of AUD dysfunction?
* Does daily SUV use change alcohol behavior and if so, is this change in behavior linked to brain-behavior change?
Participants will be randomized to a treatment group (SUV or placebo) and protocol arm, electromyography (EMG) only or EMG+functional magnetic resonance imaging (fMRI). Participants will be asked to complete the following:
* Baseline lab visit(s) that include the psychophysiological stress paradigm (EMG only or EMG+fMRI, dependent upon randomization).
* Acute drug challenge where the participant will return to the lab to repeat the stress paradigm following administration of a single dose of either 10mg SUV or placebo.
* Medication trial where participants will be instructed to take 10mg capsules of SUV or placebo orally each night before bedtime for 4-weeks.
* Daily reports of medication adherence, side-effects, sleep, alcohol use, and mood will be collected via smartphones during the 4-week medication trial.
* Post-treatment lab visit(s) where participants will return to the lab at the end of the medication trial and complete the same stress paradigm from baseline (EMG only or EMG+fMRI, dependent upon randomization).
Eligibility Criteria
Inclusion Criteria
- Age 18-65.
- Participant is able to give informed consent.
- Generally medically and physically healthy as confirmed by medical history.
- Meet DSM-5 diagnostic criteria for current moderate or severe AUD.
- Engage in heavy alcohol use defined as drinking equal or greater than 14 standard drinks per week if male and equal or greater than 7 standard drinks per week if female.
Exclusion Criteria
- Clinically significant medical or neurological condition (e.g., liver disease, narcolepsy, complex sleep behaviors, severe hepatic impairment, COPD, severe obstructive sleep apnea).
- Current cognitive dysfunction (traumatic brain injury, mental retardation, organic mental syndrome, pervasive developmental disorder, or dementia).
- Current use of antihistamines, strong or moderate inhibitors of CYP3A liver enzymes, strong CYP3A inducers, or digoxin.
- Current or past DSM-5 diagnosis of mania, schizophrenia, psychosis, suicidality, major depressive disorder, or obsessive compulsive disorder.
- Current substance use disorder other than alcohol or mild cannabis use disorder.
- Treatment seeking for AUD.
- Recent psychotropic medication use in the past 2 months.
- Currently smokes 5 or more cigarettes (or electronic equivalent) per day.
- BMI equal or greater than 35.
- Engage in night-shift work.
- Lack of fluency in English.
- Presence of ferrous-containing metal in the body.
- Inability to tolerate small, enclosed spaces.
- Deafness in one or both ears.
- Currently pregnant (positive pregnancy test), lactating, or not agreeing to use birth control methods during the duration of the trial.
Data sourced from ClinicalTrials.gov (NCT05656534). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.