Abstract
BackgroundCurrent treatments for alcohol use disorders have limited efficacy and there is a high degree of variability in treatment response. In a randomised, placebo-controlled clinical trial, there was a large effect size for topiramate in people homozygous for the GRIK1 rs2832407*C allele. The primary aim of the TOP study is to examine prospectively the therapeutic and cost-effectiveness of topiramate versus an active control (naltrexone) in improving treatment outcomes for alcohol dependence. Participants will be stratified on rs2832407 to compare C-allele homozygotes with A-allele carriers to examine the moderating effect of rs2832407 on drinking outcomes. An exploratory aim is to examine the moderating effects of rs1799971, a polymorphism in OPRM1, on the response to naltrexone by comparing Asn40 homozygotes with Asp40 carriers.Methods/designThis double-blind trial will randomise 180 alcohol-dependent participants to a 12-week regime of either topiramate (titrating the dose up to 200 mg/day) or naltrexone (50 mg/day). Participants will be stratified on the two polymorphisms before randomisation. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days per week and secondary drinking outcomes will include the time to relapse, the time to lapse and the percentage of abstinent days. Other secondary outcomes will include body mass index, tobacco use, anxiety symptoms and depressive symptoms.DiscussionIf successful, the TOP study will improve management strategies for alcohol dependence by providing support for the use of genetic biomarkers to inform medication selection.Trial registrationClinicalTrials.gov, NCT03479086. Registered on 27 March 2018.
Highlights
Current treatments for alcohol use disorders have limited efficacy and there is a high degree of variability in treatment response
Pharmacological treatment of alcohol use disorder (AUD) is widely accepted, current treatments have modest efficacy and there is a high degree of variability in treatment response
Naltrexone was selected as the comparator for this trial because it is widely available as the standard of care for the pharmacotherapy of AUD [10]
Summary
Current treatments for alcohol use disorders have limited efficacy and there is a high degree of variability in treatment response. The primary aim of the TOP study is to examine prospectively the therapeutic and cost-effectiveness of topiramate versus an active control (naltrexone) in improving treatment outcomes for alcohol dependence. Pharmacological treatment of alcohol use disorder (AUD) is widely accepted, current treatments have modest efficacy and there is a high degree of variability in treatment response. While a moderate signal of efficacy for topiramate in reducing heavy drinking has been demonstrated, there have been no well-controlled or well-powered direct comparative trials of topiramate with other commonly prescribed alcohol pharmacotherapies to guide treatment practice. There have been very few economic evaluations of commonly prescribed medications for AUD [13, 14] This absence of information on costs and potential economic benefits of treatment, given the significant burden of alcohol dependence, limits informed decision making by clinicians and policymakers
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