Recruiting
Phase 2

Brexpiprazole

Sponsor:

University of Colorado, Denver

Code:

NCT04066192

Conditions

Alcohol Use Disorder

Eligibility Criteria

Sex: All

Age: 21 - 65

Healthy Volunteers: Not accepted

Interventions

Brexpiprazole

Placebo

Study Details

Brief summary:

Few medications are currently Food \& Drug Administration (FDA)-approved for the treatment of Alcohol Use Disorder (AUD), and those that are have, on average, modest effects on drinking. "Precision medicine" research has explored whether patient-level variables, such as genetic variation, may identify subgroups of individuals with larger medication effects, but few findings have been replicated. A promising novel medication for AUD is brexpiprazole (BREX), a serotonin/dopamine activity modulator (SDAM). The investigators conducted a prior study in which the effects of another SDAM, aripiprazole, were influenced by genetic variation in the gene encoding the dopamine transporter (DAT1). This study will evaluate the effects of two doses of BREX, relative to placebo, among non-treatment-seeking individuals with AUD, and will test whether DAT1 genotype influences these effects. Primary outcomes are drinking under natural conditions and in a laboratory paradigm. Functional magnetic resonance imaging (fMRI) will be used to explore whether BREX effects on brain activation associated with cognitive control or elicited by alcohol cues accounts for its effects on drinking. The investigators hypothesize that BREX, relative to placebo, will reduce drinking under natural conditions and in the lab, and will do so to a greater extent among individuals who carry the DAT1 9-repeat allele, relative to those homozygous for the 10-repeat allele. If these hypotheses are supported, BREX may represent a novel pharmacogenetic treatment for AUD.

Conditions

Alcohol Use Disorder

Study ID

NCT04066192

Start date

Oct 30, 2020

Status verified date

Apr, 2026

Completion date

Aug 31, 2026

Anticipated

Primary completion date

Aug 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Ages 21-65.
  • Meet DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) diagnostic criteria for AUD, as assessed by the Structured Clinical Interview for DSM-5 (SCID-5).
  • Currently not engaged in, and does not want treatment for, AUD.
  • Currently not taking any medication for AUD.
  • Able to read and understand questionnaires and informed consent.
  • Lives within 50 miles of the study site.
  • Physically healthy with no history of significant medical illness.
  • Negative urine drug screen (UDS) for all substances of abuse prior to taking the first dose of medication.

Please contact clinical site for additional inclusion criteria.

Exclusion Criteria:

  • Refusal of valid written consent.
  • Insufficient English skills for consenting or interviews.
  • Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.
  • Contraindications to MRI scanning, ferrous metal in the body including intracranial, intraorbital, or intraspinal metal, pacemakers, cochlear implants or other non-MRI-compatible devices.
  • History of head injury with loss of consciousness for more than 2 minutes, neurological illness, or history of neurosurgical procedures.
  • Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
  • Current DSM-5 psychotic, mood, anxiety, obsessive-compulsive, trauma-related, or eating disorder, as assessed by SCID-5.
  • Current suicidal ideation or homicidal ideation.
  • Current use of any psychoactive medication, as evidenced by self-report and UDS.
  • History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced by self-report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar).
  • Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems, as evidenced by medical history and physical exam.
  • Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
  • Current or past hepatocellular disease, as indicated by verbal report or elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limit of the normal range at screening.
  • Females of childbearing potential who are pregnant (by plasma or urine HCG), nursing, or who are not using a reliable form of contraception.
  • Current charges pending for a violent crime (not including DUI-related offenses).
  • Currently incarcerated.
  • Lack of a stable living situation.
  • History of head injury with loss of consciousness for more than 2 minutes, neurological illness, or history of neurosurgical procedures.
  • Decisionally challenged.

Study Design

Enrollment

250 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Placebo

Participants in this Arm will take a medically inert placebo. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the capsule orally each morning.

active comparator: BREX 2mg

The BREX 2mg group will start at the same dose at the BREX 4mg group and titrate up at the same rate, so the BREX 2mg Arm will take .5 mg of brexpiprazole on day 1-2, 1 mg on day 3-4, and 2mg on day 5, to reach its final 2mg dose for day 5-14. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the medication orally each morning.

active comparator: BREX 4mg

The BREX 4mg group will start at the same dose as the BREX 2mg group and titrate up at the same rate, so the BREX 4mg Arm will take .5 mg of brexpiprazole on day 1-2, 1 mg on day 3-4, 2mg on day 5-6, and 4mg on day 7 to reach its final 4mg dose for days 7-14. To ensure pill equivalence between groups, tablets will be packaged in the same capsule; thus, each participant will take one capsule per day. Participants will be instructed to ingest the medication orally each morning.

Interventions

Brexpiprazole

Brexpiprazole will be used in .5mg, 1mg, 2mg, and 4mg doses as described in the study arms.

Placebo

A medically inert placebo medication will be used as described in the study arms.

Primary outcome measure

  • Number of drinks consumed in natural environment [ Time Frame: First 13 days of medication period ]
  • Number of drinks consumed in bar lab [ Time Frame: Day 14 of medication period ]
  • Change in alcohol cue-elicited brain activation (fMRI) [ Time Frame: 14 days - change between baseline and day 14 scan. ]

Central Contacts and Locations

Locations

University of Colorado Anschutz Medical Campus

Recruiting

Aurora, Colorado, United States, 80045

Contacts

More Information

Sponsor

University of Colorado, Denver

Last update posted

May 1, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Colorado, Denver on 2026-05-01.