Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome

AUDs are difficult to treat, and relapse rates are high, with an estimated 80% of individuals with AUDs returning to alcohol use after completing addictions treatment. Novel treatment approaches are needed to enhance long term sobriety. The investigator's research team has been investigating the use of acamprosate to prevent relapse to alcohol use. Unfortunately despite being FDA approved and endorsed by the American Psychiatric Association only 10% of patients treated for AUD are prescribed acamprosate or other antidipsotropic medications. The number is higher for patients treated in programs affiliated with Mayo Clinic Addiction Services (approximately 20%) but is way less than expected. The most common reasons behind these low numbers are the understanding that not every patient benefits from the use of specific medication and the lack of biomarkers predictive of response. The purpose of this project is to identify such biomarkers by discovery of genomic and metabolomic markers associated with response to acamprosate treatment.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Acamprosate; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 288
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Center City, Minnesota, United States, 55012
      • Hazelden Betty Ford Foundation
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Oregon
    • Newberg, Oregon, United States, 97132
      • Hazelden Betty Ford Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 to85; DSM-5 diagnosis of AUD determined by PRISM;
2. Completion of alcohol detoxification (CIWA score < 5) and no alcohol for at least 7 days (but no more than 35 days);
3. Ability to provide informed consent
4. Ability to speak English
5. Willingness to use the study medications for 3 months and attend follow-up visits.
6. No chronic/daily use of benzodiazepines, opioids, or stimulants for a period of time which is determined by 3 x the medication half-life value (see addendum A) to be completed before the initiation of study medication (acamprosate or placebo).
7. Willingness to discontinue previously prescribed acamprosate for a period of at least 3 days before randomization to study medication (acamprosate or placebo).

Exclusion Criteria:

1. Hypersensitivity or allergy to acamprosate
2. Current use of wellbutrin and not willing to switch to an acceptable antidepressant medication
3. Renal impairment (creatinine level >1.5 mg/dL);
4. Diagnosis of advanced liver disease indicated in the medical record or by a MELD score of above 10;
5. Women who are pregnant, breastfeeding, or planning to become pregnant during the next year;
6. Primary diagnosis of substance use disorder other than alcohol as determined by PRISM or in medical record review or secondary diagnosis of active (within the past year) benzo/sedative dependence, opioid dependence, stimulant dependence, heroin dependence, and/or cocaine dependence
7. Refusal to abstain from any chronic/daily use of prescribed benzodiazepines, opioids, stimulants, cannabis related medication such as CBD or medical marijuana, during the course of participation.
8. Current use of Naltrexone and not willing to stop and switch to Acamprosate/Placebo
9. Current use of Antabuse.
10. Active suicidal ideation or any unstable medical or psychiatric condition as determined by responses to PRISM or by the investigator.
11. Status of involuntary or court-ordered admission at time of consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Acamprosate; All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial. The most common side effect associated with acamprosate use is diarrhea, which occurs in approximately 16% of patients. Other frequently occurring side effects include asthenia, nausea, pruritus, and flatulence, headache, abdominal pain, flu syndrome, edema, weight gain, and myalgia.	Drug: Acamprosate; The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.
Placebo Comparator: Placebo; All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.	Other: Placebo; The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Continuous Sobriety According to Alcohol Timeline Follow Back	The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.	Will be defined as continuous sobriety (yes/no) during 3 months of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back	The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.	The number of days until first alcohol use (relapse) assessed by TLFB during 3 months of treatment
Days Until First Relapse (Heavy Relapse) - Timeline Follow Back	The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.	Number of days until first relapse (heavy relapse) between medication start and 3 months follow-up
Cumulative Abstinence Duration - Timeline Follow Back	The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.	Cumulative abstinence duration proportion: proportion of days over the length of 3 month follow-up during which participants were abstinent from alcohol use, a score range of 0 (drinking continuously) to 100 (maintain complete abstinence) is applied.

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Victor M Karpyak, MD, Ph.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): November 4, 2023
• Study Completion (Actual): November 4, 2023

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 25, 2019
• First Posted (Actual): January 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Alcohol Deterrents; Acamprosate
• Other Study ID Numbers: 18-006428; 1R01AA027486-01 (U.S. NIH Grant/Contract); 1U01AA027487 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes