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

NCT ID: NCT06471686

Last Updated: 2024-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2023-10-30

Brief Summary

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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

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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).

Conditions

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Alcohol Use Disorder Liver Transplant; Complications

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Acamprosate

Intervention Type DRUG

2 pills three times a day

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Acamprosate

2 pills three times a day

Intervention Type DRUG

Other Intervention Names

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acamprosate pills

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Hyosun Han

Assistant Professor of Clinical medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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University of Southern California

Los Angeles, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 29199144 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37314743 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32531107 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27795986 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20726963 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32226621 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36972386 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36281979 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11239123 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31758811 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33069880 (View on PubMed)

Flannery BA, Volpicelli JR, Pettinati HM. Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res. 1999 Aug;23(8):1289-95.

Reference Type BACKGROUND
PMID: 10470970 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21442687 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23276315 (View on PubMed)

Ayyala-Somayajula D, Bottyan T, Shaikh S, Lee BP, Cho SH, Dodge JL, Terrault NA, Han H. Safety of acamprosate for alcohol use disorder after liver transplant: A pilot randomized controlled trial. Liver Transpl. 2025 Apr 1;31(4):498-507. doi: 10.1097/LVT.0000000000000475. Epub 2024 Sep 3.

Reference Type DERIVED
PMID: 39225670 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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HS-19-00991

Identifier Type: -

Identifier Source: org_study_id

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