Clinical trial NCT04311294: Development of a Selective ALDH2 Inhibitor to Treat AUD
Official title: Development of a Selective ALDH2 Inhibitor for the Treatment of Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Alcohol Use Disorder
Keywords: Alcohol Use Disorder
Medications Development
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: Amygdala Neurosciences
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2020-03-17
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, triple-blind, placebo-controlled, parallel-group study of ANS-6637 (200mg, 600mg, 0mg \[palcebo\])
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

1. 21 years and older (adult, older adult);
2. meeet DSM-5 diagnostic criteria for alcohol use disorder (moderate or severe);
3. report drinking at least 48 standard drinks in a 30-day period, during the 90 days before enrollment.

Exclusion Criteria:

1. current treatment for alcohol problems;
2. a history of treatment for alcohol problems in the 30 days before enrollment;
3. currently seeking treatment for alcohol problems;
4. current DSM-5 diagnosis of dependence on any psychoactive substances other than alcohol or nicotine;
5. lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder;
6. positive urine screen for narcotics, amphetamines, or sedative hypnotics;
7. serious alcohol withdrawal symptoms as indicated by a score of ≥10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar)
8. pregnant, nursing, or refusal to use reliable birth control method (if female);
9. medical condition that may interfere with safe study participation (e.g. unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes);
10. AST, ALT, or GGT ≥ 3 times upper limit of normal;
11. attempted suicide in the past 3 years and/or serious suicidal intention or plan in the past year;
12. currently on prescription medication that contraindicates use of ANS-6637;
13. other circumstances that, in the opinion of the investigators, compromises participant safety

Primary outcomes:
measure: Change in Subjective Response to Alcohol
timeFrame: Baseline, 30-, 45-, 60-, 120-, and 180-minutes post alcohol
measure: Change in Neural Alcohol Cue Reactivity
timeFrame: Assessed on Day 4. Scan duration 1 hour.
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Addictions Lab
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Lara Ray, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Erica Grodin, PhD
role: PRINCIPAL_INVESTIGATOR
References: