Clinical trial NCT03818191: Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome
Official title: Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Alcohol Use Disorder
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2019-01-28
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Continuous Sobriety According to Alcohol Timeline Follow Back
timeFrame: Will be defined as continuous sobriety (yes/no) during 3 months of treatment
Secondary outcomes:
measure: Day Until First Alcohol Use (Relapse) - Alcohol Timeline Follow Back
timeFrame: The number of days until first alcohol use (relapse) assessed by TLFB during 3 months of treatment
measure: Days Until First Relapse (Heavy Relapse) - Timeline Follow Back
timeFrame: Number of days until first relapse (heavy relapse) between medication start and 3 months follow-up
measure: Cumulative Abstinence Duration - Timeline Follow Back
timeFrame: 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.
Other outcomes:
Locations:
city: Center City
country: United States
facility: Hazelden Betty Ford Foundation
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Newberg
country: United States
facility: Hazelden Betty Ford Foundation
state: Oregon
Study officials:
affiliation: Mayo Clinic
name: Victor M Karpyak, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: