Alcohol-related Liver Disease
Conditions
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.
Interventions
DRUGAcomprosate
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
Sponsors
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | 24 weeks | Number of adverse events reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Alcohol Craving | Baseline, week 24 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Acamprosate: Acamprosate was administered orally and was dosed at 333 mg three times a day, if tolerated it was increased to 666 mg three times a day. Acamprosate was administered for a total of 3 months | 6 |
| 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.
Acamprosate: Acamprosate was administered orally and was dosed at 333 mg three times a day, if tolerated it was increased to 666 mg three times a day. Acamprosate was administered for a total of 3 months | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Alcohol-related Liver Disease and AUD, MELD-NA Less Than 20 | Total | Alcohol-related Liver Disease and AUD, MELD-NA More Than 20 |
|---|---|---|---|
| Age, Continuous | 48 years | 50 years | 50 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 9 Participants | 4 Participants |
| Region of Enrollment United States | 6 participants | 12 participants | 6 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
Adverse Event
Number of adverse events reported
Time frame: 24 weeks
Population: One MELD-NA less than 20 subject and four MELD-NA more than 20 subjects withdrew prior to initiating the study drug. Data was not collected nor analyzed for those 5 subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alcohol-related Liver Disease and AUD, MELD-NA Less Than 20 | Adverse Event | 0 adverse events |
| Alcohol-related Liver Disease and AUD, MELD-NA More Than 20 | Adverse Event | 1 adverse events |
Secondary
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.
Time frame: Baseline, week 24
Population: One MELD-NA less than 20 subject and four MELD-NA more than 20 subjects withdrew prior to initiating the study drug. Data was not collected nor analyzed for those 5 subjects
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alcohol-related Liver Disease and AUD, MELD-NA Less Than 20 | Change in Alcohol Craving | 3 Participants |
| Alcohol-related Liver Disease and AUD, MELD-NA More Than 20 | Change in Alcohol Craving | 1 Participants |