Topiramate versus naltrexone for alcohol use disorder: study protocol for a genotype-stratified, double-blind randomised controlled trial (TOP study)

BACKGROUND: Current 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/DESIGN: This 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. DISCUSSION: If 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 REGISTRATION: ClinicalTrials.gov, NCT03479086. Registered on 27 March 2018. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13063-018-2824-z) contains supplementary material, which is available to authorized users.