Development of a Selective ALDH2 Inhibitor to Treat AUD
Primary Purpose
Alcohol Use Disorder
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ANS-6637 Low Dose
ANS-6637 High Dose
Matched Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Use Disorder focused on measuring Alcohol Use Disorder, Medications Development
Eligibility Criteria
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
Sites / Locations
- UCLA Addictions Lab
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
ANS-6637 Low Dose
ANS-6637 High Dose
Placebo
Arm Description
200mg ANS-6637 (2 tablets)
600mg ANS-6637 (2 tablets)
0mg matched placebo (2 tablets)
Outcomes
Primary Outcome Measures
Change in Subjective Response to 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.
Change in Neural Alcohol Cue Reactivity
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT04311294
First Posted
March 11, 2020
Last Updated
May 20, 2021
Sponsor
University of California, Los Angeles
Collaborators
Amygdala Neurosciences, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1. Study Identification
Unique Protocol Identification Number
NCT04311294
Brief Title
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
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Project was not funded.
Study Start Date
April 2020 (Anticipated)
Primary Completion Date
January 2022 (Anticipated)
Study Completion Date
March 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, Los Angeles
Collaborators
Amygdala Neurosciences, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder
Keywords
Alcohol Use Disorder, Medications Development
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, triple-blind, placebo-controlled, parallel-group study of ANS-6637 (200mg, 600mg, 0mg [palcebo])
Masking
ParticipantCare ProviderInvestigator
Masking Description
The study team, medical personnel, and participants will be blind to drug condition.
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ANS-6637 Low Dose
Arm Type
Active Comparator
Arm Description
200mg ANS-6637 (2 tablets)
Arm Title
ANS-6637 High Dose
Arm Type
Active Comparator
Arm Description
600mg ANS-6637 (2 tablets)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0mg matched placebo (2 tablets)
Intervention Type
Drug
Intervention Name(s)
ANS-6637 Low Dose
Intervention Description
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
Intervention Name(s)
ANS-6637 High Dose
Intervention Description
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
Intervention Name(s)
Matched Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Subjective Response to Alcohol
Description
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.
Time Frame
Baseline, 30-, 45-, 60-, 120-, and 180-minutes post alcohol
Title
Change in Neural Alcohol Cue Reactivity
Description
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.
Time Frame
Assessed on Day 4. Scan duration 1 hour.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lara Ray, PhD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Erica Grodin, PhD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA Addictions Lab
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
All data collected in this project will be shared (after appropriate de-identification) with the scientific community in a timely manner, in accordance with NIH Policy. Specifically, the dataset will be made available to the scientific community upon request and a data application will be required. These procedures are consistent with the recent NIAAA announcement: NOT-AA-18-010
Learn more about this trial
Development of a Selective ALDH2 Inhibitor to Treat AUD
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