Safety of Acamprosate in Treating Alcohol Use Disorder in the Post Liver Transplant Populations

June 25, 2024 updated by: Hyosun Han, University of Southern California
Acamprosate for alcohol use disorder may benefit liver transplant (LT) recipients with alcohol-associated liver disease (ALD), yet data on feasibility and safety in LT recipients are lacking. This was a single-center unblinded randomized controlled trial of adults (≥18 years) with LT for ALD enrolled between 2021-2023 who were randomized 2:1 to the intervention of acamprosate (666mg dose three time daily) or standard of care (SOC) for 14 weeks. The primary outcome was safety [prevalence of adverse events (AE)]. Secondary outcomes included feasibility (weekly survey response rate >60%), adherence (self reported acamprosate use>60%), and efficacy (reduction in Penn Alcohol Craving Scale [PACS]) and relapse). Relapse was defined as blood phosphatidylethanol≥20ng/mL or reported alcohol use. All analyses were done in the intention to treat (ITT) population and per-protocol population (PPP) (excluding withdrawals/acamprosate non-adherent).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Acamprosate for alcohol use disorder may benefit liver transplant (LT) recipients with alcohol-associated liver disease (ALD), yet data on feasibility and safety in LT recipients are lacking.

This was a single-center unblinded randomized controlled trial of adults (≥18 years) with LT for ALD enrolled between 2021-2023 who were randomized 2:1 to the intervention of acamprosate (666mg dose three time daily) or standard of care (SOC) for 14 weeks. The primary outcome was safety [prevalence of adverse events (AE)]. Secondary outcomes included feasibility (weekly survey response rate >60%), adherence (self reported acamprosate use>60%), and efficacy (reduction in Penn Alcohol Craving Scale [PACS]) and relapse). Relapse was defined as blood phosphatidylethanol≥20ng/mL or reported alcohol use. All analyses were done in the intention to treat (ITT) population and per-protocol population (PPP) (excluding withdrawals/acamprosate non-adherent).

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • >18 years of age
  • must have received a transplant for liver disease secondary to alcohol-associated hepatitis or alcohol-associated cirrhosis
  • greater than 24 hours of abstinence.

Exclusion Criteria:

  • patients with hypersensitivity to acamprosate calcium or any of its components
  • severe renal impairment (creatinine clearance ≤30 mL/min)
  • substance dependence other than THC, alcohol, or nicotine
  • need for inpatient detoxification or inpatient treatment of alcohol use
  • participation in a clinical trial within the past 60 days
  • women of childbearing potential without a medically acceptable form of contraception

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acamprosate
The intervention group was assigned to acamprosate 666 mg oral tablets three times daily in addition to routine medical care for 14 weeks. Once assigned to this group, participants underwent a medication reconciliation with a transplant pharmacist to ensure there were no drug-drug interactions and answer questions regarding the medication. The medication prescription was then sent by the principal investigator (HH) to the patient preferred pharmacy. The research assistants (KL and JA) would confirm that the medication was obtained. They then underwent weekly telemedicine visits with a research member for 14 weeks and filled out self-report surveys to evaluate cravings, alcohol use, and side effects
Drug: Acamprosate
2 pills three times a day
Other Names:
  • acamprosate pills
No Intervention: Standard of Care
The control group continued with what was considered routine medical care as indicated by their medical condition including frequency of clinic visits (ranging from 1-6 months dependent on time from transplant), frequency of laboratory draws (ranging from twice monthly to biannually dependent on time from transplant), and adjustment of LT related medications (i.e. immunosuppression and prophylaxis against communicable disease). They also underwent weekly telemedicine visits with a research member for 14 weeks and filled out self-report surveys to evaluate cravings, alcohol use, and side effects

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: 14 weeks
prevalence of adverse events (AE) by common toxicity criteria
14 weeks
Incidence of Treatment-Emergent Liver Test Changes
Time Frame: 14 weeks
prevalence of liver test abnormalities [aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin
14 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of acamprosate usage> 60%
Time Frame: 14 weeks
Adherence to acamprosate was measured via self-reported total milligrams of acamprosate taken weekly. Participants were deemed adherent to acamprosate to if they utilized it as prescribed for ≥60% of weeks (9 of 14 weeks).
14 weeks
Proportion of participants with weekly survey response rate >60%
Time Frame: 14 weeks
Feasibility was defined as a response rate >60% to weekly surveys in both treatment groups
14 weeks
Change in alcohol cravings
Time Frame: 14 weeks
Cravings were assessed using the validated survey Penn Alcohol Craving Scale . This is a 5 item Likert scale to measure cravings to drink alcohol within the past week with total scores ranging from 0-30. PACS scores were summarized in 4-week increments with the highest PACS score within +/- 2 weeks reported when missing at the specific time point. The median change in baseline PACS score was utilized in the analysis.
14 weeks
change in alcohol use
Time Frame: 14 weeks
Alcohol use was assessed using a modified Timeline Followback (TFLB) which is a calendar-based method to examine variability, pattern, and extent of drinking using dates to enhance recall within the past 90 days prior to enrollment at baseline and then weekly thereafter until completion of the study. number of standard alcohol drinks per day were calculated based upon the above data.
14 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2021

Primary Completion (Actual)

July 30, 2023

Study Completion (Actual)

October 30, 2023

Study Registration Dates

First Submitted

June 10, 2024

First Submitted That Met QC Criteria

June 17, 2024

First Posted (Actual)

June 24, 2024

Study Record Updates

Last Update Posted (Actual)

June 27, 2024

Last Update Submitted That Met QC Criteria

June 25, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HS-19-00991

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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