Clinical trial NCT06471686: Safety of Acamprosate in Treating Alcohol Use Disorder in the Post Liver Transplant Populations
Official title: Safety of Acamprosate in Treating Alcohol Use Disorder in the Post Liver Transplant Populations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcohol Use Disorder
Liver Transplant; Complications
Lead sponsor: University of Southern California
Sponsor class: OTHER
First posted: 2024-06-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 14 weeks
measure: Incidence of Treatment-Emergent Liver Test Changes
timeFrame: 14 weeks
Secondary outcomes:
measure: Proportion of participants with weekly survey response rate >60%
timeFrame: 14 weeks
measure: Rate of acamprosate usage> 60%
timeFrame: 14 weeks
measure: Change in alcohol cravings
timeFrame: 14 weeks
measure: change in alcohol use
timeFrame: 14 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
Study officials:
References:
citation: Cholankeril G, Ahmed A. Alcoholic Liver Disease Replaces Hepatitis C Virus Infection as the Leading Indication for Liver Transplantation in the United States. Clin Gastroenterol Hepatol. 2018 Aug;16(8):1356-1358. doi: 10.1016/j.cgh.2017.11.045. Epub 2017 Dec 1. No abstract available.
citation: Ilyas F, Ali H, Patel P, Basuli D, Giammarino A, Satapathy SK. Rising alcohol-associated liver disease-related mortality rates in the United States from 1999 to 2022. Hepatol Commun. 2023 Jun 14;7(7):e00180. doi: 10.1097/HC9.0000000000000180. eCollection 2023 Jul 1.
citation: Cotter TG, Sandikci B, Paul S, Gampa A, Wang J, Te H, Pillai A, Reddy KG, di Sabato D, Little EC, Sundaram V, Fung J, Lucey MR, Charlton M. Liver transplantation for alcoholic hepatitis in the United States: Excellent outcomes with profound temporal and geographic variation in frequency. Am J Transplant. 2021 Mar;21(3):1039-1055. doi: 10.1111/ajt.16143. Epub 2020 Aug 13.
citation: Heyes CM, Schofield T, Gribble R, Day CA, Haber PS. Reluctance to Accept Alcohol Treatment by Alcoholic Liver Disease Transplant Patients: A Qualitative Study. Transplant Direct. 2016 Sep 7;2(10):e104. doi: 10.1097/TXD.0000000000000617. eCollection 2016 Oct.
citation: DiMartini A, Dew MA, Day N, Fitzgerald MG, Jones BL, deVera ME, Fontes P. Trajectories of alcohol consumption following liver transplantation. Am J Transplant. 2010 Oct;10(10):2305-12. doi: 10.1111/j.1600-6143.2010.03232.x. Epub 2010 Aug 19.
citation: Yoo ER, Cholankeril G, Ahmed A. Treating Alcohol Use Disorder in Chronic Liver Disease. Clin Liver Dis (Hoboken). 2020 Mar 26;15(2):77-80. doi: 10.1002/cld.881. eCollection 2020 Feb.
citation: Rabiee A, Mahmud N, Falker C, Garcia-Tsao G, Taddei T, Kaplan DE. Medications for alcohol use disorder improve survival in patients with hazardous drinking and alcohol-associated cirrhosis. Hepatol Commun. 2023 Mar 24;7(4):e0093. doi: 10.1097/HC9.0000000000000093. eCollection 2023 Apr 1.
citation: Ayyala D, Bottyan T, Tien C, Pimienta M, Yoo J, Stager K, Gonzalez JL, Stolz A, Dodge JL, Terrault NA, Han H. Naltrexone for alcohol use disorder: Hepatic safety in patients with and without liver disease. Hepatol Commun. 2022 Dec;6(12):3433-3442. doi: 10.1002/hep4.2080. Epub 2022 Oct 25.
citation: Weinrieb RM, Van Horn DH, McLellan AT, Alterman AI, Calarco JS, O'Brien CP, Lucey MR. Alcoholism treatment after liver transplantation: lessons learned from a clinical trial that failed. Psychosomatics. 2001 Mar-Apr;42(2):110-6. doi: 10.1176/appi.psy.42.2.110.
citation: Rogal S, Youk A, Zhang H, Gellad WF, Fine MJ, Good CB, Chartier M, DiMartini A, Morgan T, Bataller R, Kraemer KL. Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis. Hepatology. 2020 Jun;71(6):2080-2092. doi: 10.1002/hep.31042. Epub 2020 May 22.
citation: Im GY, Mellinger JL, Winters A, Aby ES, Lominadze Z, Rice J, Lucey MR, Arab JP, Goel A, Jophlin LL, Sherman CB, Parker R, Chen PH, Devuni D, Sidhu S, Dunn W, Szabo G, Singal AK, Shah VH. Provider Attitudes and Practices for Alcohol Screening, Treatment, and Education in Patients With Liver Disease: A Survey From the American Association for the Study of Liver Diseases Alcohol-Associated Liver Disease Special Interest Group. Clin Gastroenterol Hepatol. 2021 Nov;19(11):2407-2416.e8. doi: 10.1016/j.cgh.2020.10.026. Epub 2020 Oct 16.
citation: Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res. 1999 Aug;23(8):1289-95.
citation: Rief W, Barsky AJ, Glombiewski JA, Nestoriuc Y, Glaesmer H, Braehler E. Assessing general side effects in clinical trials: reference data from the general population. Pharmacoepidemiol Drug Saf. 2011 Apr;20(4):405-15. doi: 10.1002/pds.2067. Epub 2010 Nov 8.
citation: Robinson SM, Sobell LC, Sobell MB, Leo GI. Reliability of the Timeline Followback for cocaine, cannabis, and cigarette use. Psychol Addict Behav. 2014 Mar;28(1):154-62. doi: 10.1037/a0030992. Epub 2012 Dec 31.