Acamprosate Safe to Use in Individuals With Liver Disease.

Study Overview
=================
Brief Summary
-----------------
Is acamprosate safe to use in individuals with liver disease.

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.

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

Conditions
-----------------
Alcohol-related Liver Disease

Intervention / Treatment
-----------------
* Drug: Acomprosate


Participation Criteria
=================
Eligibility Criteria
-----------------
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).

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alcohol-related liver disease and AUD, MELD-NA less than 20<br>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<br>* 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<br>|
| Experimental: Alcohol-related liver disease and AUD, MELD-NA more than 20<br>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<br>* 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<br>|

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 |