Development of a Selective ALDH2 Inhibitor to Treat AUD
Status:
Withdrawn
Trial end date:
2022-03-01
Target enrollment:
Participant gender:
Summary
Alcohol use disorder (AUD) represents a highly prevalent, costly, and often untreated
condition in the United States. Pharmacotherapy offers a promising avenue for treating AUD
and for improving clinical outcomes for this debilitating disorder. While developing novel
medications to treat AUD remains a high priority research area, there are major opportunities
to refine the process of screening novel compounds.
A promising novel pharmacology for AUD consists of the ANS-6637 compound which provides novel
aldehyde dehydrogenase 2 (ALDH2) inhibition. Unlike disulfiram, a non-selective and
irreversible ALDH2 and ALDH1 inhibitor, which produces an aversive flushing response, the
oral ANS-6637 compound is a selective and reversible inhibitor of ALDH2 that attenuates the
surge in dopamine (DA). Specifically, a preclinical study found that ANS-6637 blunted the
surge of DA in ventral tegmental neurons without affecting the basal levels of DA in vivo in
a rodent model of alcohol seeking behavior. In rodent models, selective and reversible ALDH2
inhibitors decrease alcohol seeking and taking, prevent operant self-administration, and
block cue-induced reinstatement. These results suggest that ANS-6637 may be an effective
treatment to reduce heavy drinking and suppress relapse in individuals with AUD.
This is a randomized, double-blind, placebo-controlled, dose response study of ANS-6637. A
total of 75 men and women with current AUD will be randomly assigned to receive (a) ANS-6637
(200 mg), (b) ANS-6637 (600 mg), or (c) matched placebo for 7 days. On Day 4, participants
will complete an fMRI task before and 45-minutes after a priming dose of alcohol (target
Breath Alcohol Concentration (BrAC) of 0.03 g/dl). On Day 7 participants will return to the
laboratory to complete an oral alcohol administration paradigm. The successful completion of
this study will advance medications development for AUD by advancing the development of
ANS-6637, a novel and promising compound for AUD.
Phase:
Phase 2
Details
Lead Sponsor:
University of California, Los Angeles
Collaborators:
Amygdala Neurosciences National Institute on Alcohol Abuse and Alcoholism (NIAAA)