Brexpiprazole in Alcohol Use Disorder

NCT04066192 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19-16581R01AA027765-01
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• Number of drinks consumed in natural environment

  The number of standard alcoholic drinks participants consume during the first 13 days of the medication period, as reported on the Timeline Follow-Back Interview.

  First 13 days of medication period

• Number of drinks consumed in bar lab

  The number of drinks (out of 8 possible) that participants choose to consume in the bar lab.

  Day 14 of medication period

• Change in alcohol cue-elicited brain activation (fMRI)

  Magnitude of change between baseline and day 14 fMRI scan in the blood oxygenation level dependent (BOLD) signal to alcohol cues, relative to neutral beverage cues on the Alcohol Cue Reactivity Task.

  14 days - change between baseline and day 14 scan.

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

BREX 2mg

ACTIVE COMPARATOR

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.

Drug: Brexpiprazole

BREX 4mg

ACTIVE COMPARATOR

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.

Drug: Brexpiprazole

Interventions

Brexpiprazole DRUG

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

BREX 2mg; BREX 4mg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Related Publications (1)

• Schacht JP, Voronin KE, Randall PK, Anton RF. Dopaminergic Genetic Variation Influences Aripiprazole Effects on Alcohol Self-Administration and the Neural Response to Alcohol Cues in a Randomized Trial. Neuropsychopharmacology. 2018 May;43(6):1247-1256. doi: 10.1038/npp.2017.298. Epub 2017 Dec 6.

  PMID: 29362512 BACKGROUND

MeSH Terms

Conditions

Alcoholism

Interventions

brexpiprazole

Condition Hierarchy (Ancestors)

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

Study Officials

• Joseph P Schacht, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph P Schacht, PhD

CONTACT

303-724-3773; joseph.schacht@cuanschutz.edu

Kristen M Raymond

CONTACT

303-724-3196; kristen.raymond@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be blind to medication assignment, as will all care providers and investigators.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind placebo controlled clinical trial.

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 26, 2019
• Study Start: October 30, 2020
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will become available 2 years after the grant end date, and will be available as long as the NDA exists.
• Access Criteria: Investigators at institutions with a Federal Wide Assurance (FWA) will be able to gain access to NDA data by submitting a data access request in accordance with applicable NDA policies (see https://ndar.nih.gov/access.html for sample policies). Data requests will be reviewed and granted by a NIAAA Data Access Committee.

Locations

US (1)