Suvorexant for Alcohol Use Disorder (AUD): Neural Mechanisms

NCT06484075 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001561001561-AA
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Alcohol use disorder (AUD) is a leading cause of disease and death worldwide. New treatments for AUD are needed. Dopamine, a chemical that carries signals between brain cells, is thought to play a role in alcohol addiction. Researchers want to learn how Suvorexant, a drug used to treat sleep disorders, affects dopamine receptors in the brain. Objective: To see how Suvorexant affects dopamine receptors in people with AUD and in healthy people. Eligibility: People aged 18 to 75 years seeking treatment for AUD. Healthy volunteers are also needed. Design: Participants with AUD will stay in the clinic for at least 10-28 days for alcohol detoxification. They will receive normal treatment for AUD. Suvorexant is a medicine used to treat sleep problem that is taken taken by mouth, once a day. Some participants will take the study drug. Others will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which they are taking. Participants will wear a device that looks like a wristwatch to track their movements during their clinic stay. Participants will have blood tests and 3 brain imaging scans before starting on the study drug: 2 positron emission tomography (PET) and 1 magnetic resonance imaging (MRI) scan. They will be injected with a radioactive tracer during each PET scan. Participants will have tests to assess their thinking, memory, and attention. They will have sleep studies. Imaging scans and other tests will be repeated at the end of the study. Healthy volunteers will have 1 MRI and 2 PET scans. They will have tests to assess of their thinking, memory, and attention. They will wear a wristwatch like movement monitor for 1 week. ...

Conditions

Healthy Volunteers; Alcohol Use Disorder (AUD)

Keywords

Suvorexant; Sleep; Dopamine D2R; Dopamine D1R; Alcohol Use Disorder (AUD); Alcohol Craving

Outcome Measures

Primary Outcomes (1)

• To examine the impact of suvorexant on dopamine receptors in adults with AUD undergoing detoxification and to compare against baseline measures in healthy controls.

  We hypothesize that suvorexant compared to placebo will (1) increase striatal dopamine D2 receptors while decreasing the balance of D1 to D2 receptor signaling (D1R/D2R) and (2) improve sleep and reduce alcohol craving and dysphoria.

  3 years

Secondary Outcomes (1)

• To examine suvorexant's effects on sleep quality and alcohol craving in adults with AUD undergoing detoxification.

  3 years

Study Arms (3)

Non treatment

NO INTERVENTION

Healthy Volunteers will receive two PET scans and one MRI session without any treatment.

Placebo

PLACEBO COMPARATOR

AUD subjects randomized to receive placebo for up to 28 days during inpatient treatment.

Drug: Placebo

Suvorexant

ACTIVE COMPARATOR

AUD subjects randomized to receive Suvorexant (20 mg po) for up to 28 days during inpatient treatment.

Drug: Suvorexant

Interventions

Placebo DRUG

The placebo will be a tablet, but only containing inert inactive ingredients.

Placebo

Suvorexant DRUG

Drug approved for improving sleep

Suvorexant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All Participants
• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, ages 18-75 years old.
• Ability to understand and the willingness to sign a written informed consent document.
• AUD Participants
• DSM 5 diagnosis of moderate or severe AUD.
• Participants seeking treatment for their AUD.
• Current AUD with minimum 5-year lifetime history of heavy drinking (SAMSHA's criteria for heavy drinking: for men 5 or more drinks/day on at least 5 different days per month; and for women 4 or more drinks/day on at least 5 different days per month).
• Last alcohol use within the 7 days prior to enrollment in the Natural History protocol 14AA0181.
• Self-reported insomnia/sleep problems: PSQI score \> 4 and/or endorsing "problems falling asleep or staying asleep throughout the night".
• Ability to take oral medication and be willing to adhere to the suvorexant/placebo regimen.
• Agreement to commit to at least 28 days, and up to 40 days, inpatient stay (starting from Natural History protocol enrollment).
• Agreement to adhere to Lifestyle Considerations throughout study duration.

You may not qualify if:

• All Participants
• An individual who meets any of the following criteria will be excluded from participation:
• Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head, fear of enclosed spaces, or other standard contraindication to MRI.
• Cannot lie comfortably flat on his/her back for up to 2 hours in the MRI scanner.
• Body weight \> 400 lbs. The PET scanner bed is tested to a weight limit of 400 lbs.
• Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits as determined by medical history and physical exam.
• Pregnant or breast-feeding: Females of childbearing potential, or with tubal ligation, or are post-menopausal and are age 55 or less will undergo a urine pregnancy test and it must be negative to continue participation. Urine pregnancy tests will be repeated on subsequent days of study (i.e., within 24 hours before study procedures). Females must not be currently breastfeeding.
• Severe head trauma with loss of consciousness \> 60 minutes.
• Chronic recurrent primary psychotic disorders like schizophrenia and bipolar 1 disorder.
• Montgomery-Asberg depression rating scale (MADRS) total score \> 35 or 'suicidal thoughts' item score \> 3, indicating severe depression or moderate suicidality, respectively.
• Major medical problems that can permanently impact brain function (e.g., seizures, psychosis, stroke, Alzheimer's disease, Parkinson's disease, traumatic brain injury, clinically significant arrhythmias except bradycardia, and HIV+).
• Hepatic enzymes (ALT/GPT, AST/GOT, Total Bilirubin, Direct Bilirubin) that are \>5x the upper limit of normal, indicating severe hepatic impairment.
• Non-English speakers (must also be able to read and comprehend English).
• The intent of the research has no prospect of direct benefit to the subject. Therefore, we are excluding non-English speakers in this research study since it includes the administration of questionnaires, surveys and assessments that are validated for English; only some are available in Spanish. In addition, our fMRI paradigms require that the subject be able to speak, read and comprehend English.
• AUD Participants

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alcoholism

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Nora D Volkow Adler, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michele-Vera I Yonga, C.R.N.P.

CONTACT

(301) 273-4169; michelevera.yonga@nih.gov

Nora D Volkow Adler, M.D.

CONTACT

(301) 443-6480; nvolkow@nida.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2024
• First Posted: July 3, 2024
• Study Start: November 21, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 15, 2026

Record last verified: 2026-05-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)