Alcohol Use Disorder, Liver Transplant; Complications
Conditions
Brief summary
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).
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).
Interventions
DRUGAcamprosate
2 pills three times a day
Sponsors
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 14 weeks | prevalence of adverse events (AE) by common toxicity criteria |
| Incidence of Treatment-Emergent Liver Test Changes | 14 weeks | prevalence of liver test abnormalities \[aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with weekly survey response rate >60% | 14 weeks | Feasibility was defined as a response rate \>60% to weekly surveys in both treatment groups |
| Rate of acamprosate usage> 60% | 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). |
| Change in alcohol cravings | 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. |
| change in alcohol use | 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. |
Countries
United States
Outcome results
None listed