Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome

NCT03818191 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: 18-0064281R01AA027486-011U01AA027487
• Study Type: interventional
• Target: 288
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back

  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

  Number of days until first relapse (heavy relapse) between medication start and 3 months follow-up

• Cumulative Abstinence Duration - Timeline Follow Back

  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.

Study Arms (2)

Acamprosate

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.

Other: Placebo

Interventions

Acamprosate DRUG

The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.

Acamprosate

Placebo OTHER

The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to85; DSM-5 diagnosis of AUD determined by PRISM;
• Completion of alcohol detoxification (CIWA score \< 5) and no alcohol for at least 7 days (but no more than 35 days);
• Ability to provide informed consent
• Ability to speak English
• Willingness to use the study medications for 3 months and attend follow-up visits.
• 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).
• Willingness to discontinue previously prescribed acamprosate for a period of at least 3 days before randomization to study medication (acamprosate or placebo).

You may not qualify if:

• Hypersensitivity or allergy to acamprosate
• Current use of wellbutrin and not willing to switch to an acceptable antidepressant medication
• Renal impairment (creatinine level \>1.5 mg/dL);
• Diagnosis of advanced liver disease indicated in the medical record or by a MELD score of above 10;
• Women who are pregnant, breastfeeding, or planning to become pregnant during the next year;
• 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
• 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.
• Current use of Naltrexone and not willing to stop and switch to Acamprosate/Placebo
• Current use of Antabuse.
• Active suicidal ideation or any unstable medical or psychiatric condition as determined by responses to PRISM or by the investigator.
• Status of involuntary or court-ordered admission at time of consent.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (3)

Hazelden Betty Ford Foundation

Center City, Minnesota, 55012, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Hazelden Betty Ford Foundation

Newberg, Oregon, 97132, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Alcoholism

Interventions

Acamprosate

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

Inpatient treatment centers were closed for a period of time and subsequently admission numbers were decreased to accommodate social distancing requirements during the COVID pandemic leading to lower recruitment.

Results Point of Contact

• Title: Victor Karpyak, MD, PhD
• Organization: Mayo Clinic

karpyak.victor@mayo.edu

(507)284-8891

Study Officials

• Victor M Karpyak, MD, Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 14, 2019
• First Posted: January 28, 2019
• Study Start: July 15, 2019
• Primary Completion: November 4, 2023
• Study Completion: November 4, 2023
• Last Updated: December 17, 2024
• Results First Posted: December 17, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)