Acamprosate Safe to Use in Individuals With Liver Disease.

A Phase II Study Evaluating the Safety of Acamprosate for Alcohol Use Disorder in Alcohol-related Liver Disease

Is acamprosate safe to use in individuals with liver disease.

Study Overview

• Status: Completed
• Conditions: Alcohol-related Liver Disease
• Intervention / Treatment: Drug: Acomprosate

Detailed Description

Adult patients aged 21 or over with a diagnosis of alcohol-related liver disease and alcohol use disorder (AUD) and abstinent from alcohol for at least 2 weeks (but not more than 6 months) prior to initiating acamprosate treatment.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Aged 21 or over

• Diagnosis of alcohol-related liver disease and AUD.

  • The diagnosis of alcohol-related liver disease will be determined by a hepatologist based on history of regular and excessive alcohol consumption in the absence of other causes of liver cirrhosis or acute hepatitis, compatible clinical, imaging and laboratory findings and typical histology on liver biopsy, if performed. Underlying liver disease may include alcoholic hepatitis, advanced (F3-F4) fibrosis, and/or portal hypertension.
  • The diagnosis of AUD will be determined by a hepatologist and/or addiction psychiatrist based on history obtained that is consistent with DSM-5 diagnostic criteria for AUD (all categories of mild, moderate and severe considered eligible) (American Psychiatric Association, 2013; questions from NIH, 2016).
• Abstinent from alcohol for at least 2 weeks (but not more than 6 months) prior to initiating acamprosate treatment.
• At study enrollment, initial MELD-Na score must be less than 20 for the five individuals enrolling in the first phase of the pilot safety assessment. The second phase of the pilot safety assessment will include individuals with a MELD-Na of 20 or more at enrollment.
• Have capacity to provide consent themselves

Exclusion criteria:

• Individuals with a glomerular filtration rate (GFR) of less than 30 ml/min
• Congestive heart failure (NYHA class II or higher)
• Hypotension, requiring the use of vasoconstrictors (i.e. midodrine)
• Pregnancy, lactation or refusal to use a reliable method of birth control if a sexually active female of childbearing potential. Although no human trial data is available, animal studies suggest possible teratogenic effects of acamprosate (Merck, 2005).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alcohol-related liver disease and AUD, MELD-NA less than 20; The first 5 patients enrolled = AUD (alcohol use disorder) w/MELD-Na (model for end stage liver disease sodium) score less than 20.	Drug: Acomprosate; Acamprosate will be administered orally and will be dosed at 333 mg three times a day, if tolerated it will be increased to 666 mg three times a day. Acamprosate will be administered for a total of 3 months
Experimental: Alcohol-related liver disease and AUD, MELD-NA more than 20; The second 5 patients enrolled = AUD (alcohol use disorder) w/MELD-Na (model for end stage liver disease sodium) score more than 20.	Drug: Acomprosate; Acamprosate will be administered orally and will be dosed at 333 mg three times a day, if tolerated it will be increased to 666 mg three times a day. Acamprosate will be administered for a total of 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event	Number of adverse events reported	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Alcohol Craving	Number of subjects who experienced a decrease or unchanged Pennsylvania Alcohol Craving Scale (PACS) score from baseline to week 24. Measured using self-reported questionnaire using Pennsylvania Alcohol Craving Scale (PACS). The PACS has 5 questions, where each question has six options presented in Likert Scales from 0 to 6, with 0 being the least and 6 being the highest possible option, thus the possible minimum and maximum values are 0 and 30, respectively. Higher score indicates a positive alcohol craving symptom.	Baseline, week 24

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Douglas A Simonetto, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): January 5, 2022
• Study Completion (Actual): January 5, 2022

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 27, 2020

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: November 29, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: 18-010902

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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