The efficacy and biobehavioural basis of baclofen in the treatment of alcoholic liver disease: study protocol for a multi-site randomised controlled trial

Introduction and Aims: Effective treatments for alcohol use disorders
in those with significant liver disease are critically lacking.The
primary aim of the current study is to explore the effectiveness and
biobehavioural basis of low and high dose baclofen in improving
treatment outcomes for alcohol dependence in people with alcoholic
liver disease (The BacALD study).
Design and Methods: This double-blind, placebo-controlled study
will randomise 120 participants to a 12-week regime of either two
doses of baclofen (10 mg t.i.d vs. 25 mg t.i.d) or placebo. Participants
must meet the ICD-10 criteria for alcohol dependence in addition to
alcoholic liver disease defined as the presence of symptoms and/or
signs referable to liver disease or its complications with or without
cirrhosis. Primary outcome measures will include total abstinence
duration, time to lapse and relapse. Furthermore, 60 of the alcoholic
liver disease patients enrolled in the trial will also participate in a
pharmacokinetic and cue-reactivity component along with an additional
30 healthy volunteers matched for age and gender randomised
to either one week regime of 30 mg/day baclofen or 75 mg/day
baclofen. At week 1, plasma levels of baclofen and β-p-chlorophenol-
γ-hydroxybutric acid will be measured at zero, one and four hours
following baclofen administration and psychophysiological responses
to alcohol-associated stimuli will be assessed in a cue reactivity
paradigm.
Results: Recruitment commenced in late March 2013.Thus far the
sample consists of 50% males, with an average age of 55, 20+ years of
alcohol use and two-thirds of patients classified as Child-Pugh B
(significant functional compromise) for severity of liver disease.
Average alcohol consumption is 9.3 standard drinks per drinking day
at a rate of six days/week during the previous month before enrolment,
although the majority of patients were drinking over twice the
baseline amount during their heaviest lifetime consumption. Adherence
to the research protocol is 83%.
Discussion and Conclusions: This trial will demonstrate the efficacy
and safety of two doses of baclofen in patients with alcoholic
liver disease and will explore the biobehavioural mechanisms of the
treatment effect.