- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04311294
Development of a Selective ALDH2 Inhibitor to Treat AUD
Development of a Selective ALDH2 Inhibitor for the Treatment of Alcohol Use Disorder
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90095
- UCLA Addictions Lab
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 21 years and older (adult, older adult);
- meeet DSM-5 diagnostic criteria for alcohol use disorder (moderate or severe);
- report drinking at least 48 standard drinks in a 30-day period, during the 90 days before enrollment.
Exclusion Criteria:
- current treatment for alcohol problems;
- a history of treatment for alcohol problems in the 30 days before enrollment;
- currently seeking treatment for alcohol problems;
- current DSM-5 diagnosis of dependence on any psychoactive substances other than alcohol or nicotine;
- lifetime DSM-5 diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder;
- positive urine screen for narcotics, amphetamines, or sedative hypnotics;
- serious alcohol withdrawal symptoms as indicated by a score of ≥10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar)
- pregnant, nursing, or refusal to use reliable birth control method (if female);
- medical condition that may interfere with safe study participation (e.g. unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes);
- AST, ALT, or GGT ≥ 3 times upper limit of normal;
- attempted suicide in the past 3 years and/or serious suicidal intention or plan in the past year;
- currently on prescription medication that contraindicates use of ANS-6637;
- other circumstances that, in the opinion of the investigators, compromises participant safety
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: ANS-6637 Low Dose
200mg ANS-6637 (2 tablets)
|
ANS-6647 is a selective, reversible, and orally bioavailable aldehyde dehydrogenase 2 (ALDH2) inhibitor.
It will be tested at a low dose (200mg) and a high dose (600mg) against matched placebo.
|
Active Comparator: ANS-6637 High Dose
600mg ANS-6637 (2 tablets)
|
ANS-6647 is a selective, reversible, and orally bioavailable aldehyde dehydrogenase 2 (ALDH2) inhibitor.
It will be tested at a low dose (200mg) and a high dose (600mg) against matched placebo.
|
Placebo Comparator: Placebo
0mg matched placebo (2 tablets)
|
ANS-6647 is a selective, reversible, and orally bioavailable aldehyde dehydrogenase 2 (ALDH2) inhibitor.
It will be tested at a low dose (200mg) and a high dose (600mg) against matched placebo.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Subjective Response to Alcohol
Time Frame: Baseline, 30-, 45-, 60-, 120-, and 180-minutes post alcohol
|
Participants will complete an oral alcohol challenge and will rate their subjective responses to alcohol at baseline (BrAC = 0.00 g/dl) and at 30, 45, 60, 120, and 180 minutes post alcohol.
The primary outcome variables will be (a) alcohol craving, (b) stimulant/reward, and (c) sedative/aversive effects of alcohol.
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Baseline, 30-, 45-, 60-, 120-, and 180-minutes post alcohol
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Change in Neural Alcohol Cue Reactivity
Time Frame: Assessed on Day 4. Scan duration 1 hour.
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Participants will complete a neuroimaging paradigm in which they view alcoholic and non-alcoholic beverage cues and will rate their subjective craving for alcohol.
The primary outcome variable will be BOLD activation to alcohol cues in mesocorticolimbic reward circuitry.
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Assessed on Day 4. Scan duration 1 hour.
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Collaborators and Investigators
Investigators
- Principal Investigator: Erica Grodin, PhD, University of California, Los Angeles
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1R21AA028444
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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