Development of a Selective ALDH2 Inhibitor to Treat AUD

NCT ID: NCT04311294

Last Updated: 2021-05-25

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-30
• Study Completion Date: 2022-03-31

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.

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

ANS-6637 Low Dose

200mg ANS-6637 (2 tablets)

Group Type: ACTIVE_COMPARATOR

ANS-6637 Low Dose

Intervention Type: DRUG

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.

ANS-6637 High Dose

600mg ANS-6637 (2 tablets)

Group Type: ACTIVE_COMPARATOR

ANS-6637 High Dose

Intervention Type: DRUG

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

0mg matched placebo (2 tablets)

Group Type: PLACEBO_COMPARATOR

Matched Placebo

Intervention Type: DRUG

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.

Interventions

ANS-6637 Low Dose

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.

Intervention Type: DRUG

ANS-6637 High Dose

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.

Intervention Type: DRUG

Matched Placebo

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amygdala Neurosciences

UNKNOWN

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Lara Ray, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lara Ray, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Erica Grodin, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Locations

UCLA Addictions Lab

Los Angeles, California, United States

Countries

United States

Other Identifiers

1R21AA028444

Identifier Type: -

Identifier Source: org_study_id