Baclofen in the Treatment of Alcohol Dependence With or Without Alcoholic Liver Disease

Study Overview
=================
Brief Summary
-----------------
To explore the effectiveness and biobehavioural basis of baclofen in improving treatment outcomes for alcohol dependence in people with or without alcoholic cirrhosis in a double-blind randomised placebo-controlled trial.

Detailed Description
-----------------
This is a double-blind randomised placebo-controlled study investigating the efficacy of baclofen for the treatment of alcohol dependence in patients with alcoholic liver disease. Medications will be given for 12 weeks, with a further 6 months follow-up. Both male and female participants will be recruited to this study. Trial patients will be randomised to one of three treatment groups: (1) baclofen 30mg/day (10 mg t.i.d), (2) baclofen 75mg/day (25 mg t.i.d) or (3) Placebo (3 matched tabs/day). This study will also include a second, parallel group of patients with alcohol dependence (non alcoholic-liver disease patients) that will undergo the trial protocol as described above. These patients will be randomised according to a separate list into one of three treatment groups: (1) baclofen 30mg/day (10 mg t.i.d), (2) baclofen 75mg/day (25 mg t.i.d) or (3) Placebo (3 matched tabs/day).

Official Title
-----------------
Exploring the Efficacy and Biobehavioural Basis of Baclofen in the Treatment of Alcoholic Liver Disease

Conditions
-----------------
Alcoholic Liver Disease, Alcohol Dependence

Intervention / Treatment
-----------------
* Drug: Baclofen 30mg/day
* Drug: Baclofen 75mg/day
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ALD (for trial group 1), defined as the presence of symptoms and/or signs referable to liver disease with or without cirrhosis, in which alcohol use is considered to play a major aetiological role. Alcohol use will have exceeded an average of 60g/day in women and 80g/day in men for >10 years. Alcohol dependence according to the ICD-10 criteria (for both trial 1 and 2) Adequate cognition and English language skills to give valid consent and complete research interviews Willingness to give written informed consent Abstinence from alcohol for between 3 and 21 days Resolution of any clinically evident alcohol withdrawal (CIWA-AR) Exclusion Criteria: Active major psychological disorder associated with psychosis or significant suicide risk Pregnancy or lactation Concurrent use of any psychotropic medication other than antidepressants Substance use other than nicotine if unstable Clinical evidence of persisting hepatic encephalopathy Pending incarceration Lack of stable housing Active peptic ulcers Unstable diabetes mellitus

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Baclofen low dose | Drug: Baclofen 30mg/day<br>* 30mg/day 10 mg t.i.d<br>|
| Experimental: Arm 2<br>Baclofen high dose | Drug: Baclofen 75mg/day<br>* 75mg/day 25 mg t.i.d<br>|
| Placebo Comparator: Arm 3<br>Placebo | Drug: Placebo<br>* Placebo 3 matched tabs/day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| alcohol consumption | as measured by the number of days abstinent, number of heavy drinking days, time to relapse, time to lapse and number of drinks per drinking day | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical markers of liver injury |  | 12 weeks | 
| incidence of hepatic side effects |  | 12 weeks | 
| craving for alcohol |  | 12 weeks | 
| early termination due to side effects |  | 12 weeks |