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.
Phase:
Phase 2
Details
Lead Sponsor:
University of Colorado, Denver
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)