A Pharmacogenetic Human Laboratory Investigation of Brexpiprazole in Alcohol Use Disorder
University of Colorado, Denver
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.
Description
The overarching hypothesis of this study is that brexpiprazole (BREX) (2 or 4 mg/day), relative to placebo, will reduce alcohol consumption and modulate the neural substrates of moderate-severe Alcohol Use Disorder (AUD), and that genotype at a variable number tandem repeat polymorphism (VNTR) in the DAT1/SLC6A3 gene will predict BREX effects. Participants will be non-treatment-seeking AUD individuals, and will be prospectively randomized to medication on the basis of their DAT1 VNTR genotype. Since BREX affects both cortical and striatal neurophysiology, the investigators will use functional…
Eligibility
- Age range
- 21–65 years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- DrugBrexpiprazole
Brexpiprazole will be used in .5mg, 1mg, 2mg, and 4mg doses as described in the study arms.
- DrugPlacebo
A medically inert placebo medication will be used as described in the study arms.
Location
- University of Colorado Anschutz Medical CampusAurora, Colorado