Efficacy of Baclofen Vs Naltrexon in Achieving & Maintaining Abstinence in Alcohol Dependence.

Study Overview
=================
Brief Summary
-----------------
ALD is the most common cause of liver cirrhosis in western world. In patients with ALD persistent alcohol intake is associated with increased mortality while cessation of alcohol consumption improve survival. Baclofen is GABA-B receptor agonist and it is safe in cirrhotic patient for alcohol abstinence i.e. already proven and naltrexone is Delta and k-opioid receptor antagonist and it is safe in cirrhotic for alcohol abstinence i.e, proven in ILBS.

Detailed Description
-----------------
Aim and Objective: • To compare the efficacy of Naltrexone Vs Baclofen in achieving and maintaining 12-week abstinence in patients with alcohol associated liver cirrhosis with continued alcohol use Primary objective: The comparison in the proportion of patients achieving and maintaining alcohol abstinence between Naltrexone and Baclofen in alcohol associated liver cirrhosis patients with continued alcohol intake at 12 weeks Secondary objectives: To evaluate drinking pattern before and after 4 week on Naltrexone without liver related adverse effects compared to baclofen To evaluate proportion of patients maintaining abstinence from alcohol in both the group at 24 weeks To evaluate difference in craving measures between groups at 4, 8,12 and 24 weeks To evaluate difference in alcohol free days between groups at 4, 8,12 and 24 weeks To evaluate proportion of patients developing lapse and relapse in both the group at 4,8,12 and 24 weeks To evaluate the progression of liver disease in both group Methodology: Study population: All patients aged ≥ 18 years and ≤ 65 years admitted in Institute of Liver and Biliary Sciences, New Delhi with alcohol dependence in compensated liver disease and are giving written consent for participation in the study. Study design - Single center, Open label, Randomized controlled trial Study period - 1.5 years after IEC approval. Sample size - We are enrolling 110 patients, with 55 in each arm. Intervention - Naltrexon group: Naltrexone 50mg orally once daily will give for 12 weeks. Baclofen group: Baclofen 10mg orally thrice daily will give for 12 weeks. Monitoring and assessment: Follow up- weekly in first month and 2nd weekly there after LFT (AST, ALT, GGT, Albumin, INR), CBC with MCV, KFT at every visit At every visit Review of drinking and assessment of abstinence, lapses and relapses from alcohol Overall functioning, quality of life, social relationships Difficulties with treatment adherence (pill counts) Adverse effects - drug/ withdrawal related Psychological support and counselling at every visit by psychiatrist Statistical Analysis: The data will be represented as mean±SD. The categorical data will be analysed using Chi-square test. The continuous data will be analysed by student T test, or Mann-Whitney test, whichever is applicable. Besides this, Cox regression will be applied to analyse the variables. For all tests, p≤ 0.05 will be considered statistically significant Adverse effects Headaches, nausea, dyspepsia, anorexia, anxiety and sedation. Stopping rule Worsening of liver disease severity to CTP >9 AST or ALT > 5 times ULN Withdrawal of consent New onset decompensation Worsening of Bilirubin > 5 mg/dl Expected outcome of the project: - To achieve abstinence in both the group without affecting the liver.

Official Title
-----------------
Efficacy of Baclofen Vs Naltrexon in Achieving & Maintaining Abstinence in Alcohol Dependence.

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

Intervention / Treatment
-----------------
* Drug: Naltrexon
* Drug: Baclofen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All consecutive alcohol related compensated cirrhotic patients with continued alcohol consumption despite counselling in last 4 weeks aged between 18 - 65yrs Fulfilling DSM - 5 criteria for alcohol use disorder (Association, 2013) History of recent recidivism / relapse Exclusion Criteria: Current HE Total Bilirubin > 5 mg/dl Recent bleed Treatment with corticosteroids within the past 60 days Unwilling to participate Dependence on any other substance (except Nicotine) Psychotic disorder requiring treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Naltrexone<br>Naltrexone 50mg orally once daily will give for 12 weeks | Drug: Naltrexon<br>* Naltrexone 50mg orally once daily will give for 12 weeks<br>|
| Active Comparator: Baclofen<br>Baclofen 10mg orally thrice daily will give for 12 weeks | Drug: Baclofen<br>* Baclofen 10mg orally thrice daily will give for 12 weeks<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The comparison in the proportion of patients achieving and maintaining alcohol abstinence between Naltrexone and Baclofen in alcohol associated liver cirrhosis patients with continued alcohol intake at 12 weeks |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate abstinence rate by OCDS score in both the group (OCDS- Obsessive compulsive drinking scale 0-40, Higher total score indicate more obsessive thoughts or compulsive behaviour regarding alcohol use) |  | 4 weeks | 
| To evaluate proportion of patients maintaining abstinence from alcohol in both the group at 24 weeks |  | 24 weeks | 
| To evaluate difference in craving measures between groups at 4,8,12 and 24 weeks. | Craving measures will be assessed based on pre existing structured and validated questionnaires. (Visual analogue scale (VAS) score, score 0-10, 10 suggestive of maximum craving). | 4, 8,12 and 24 weeks | 
| To evaluate difference in alcohol free days between groups at 4, 8,12 and 24 weeks |  | 4, 8,12 and 24 weeks | 
| To evaluate proportion of patients developing lapse and relapse in both the group at 4,8,12 and 24 weeks |  | 4,8,12 and 24 weeks | 
| To evaluate the progression of liver disease in both group at 24weeks by measuring Child pugh score. |  | 24 weeks |