A Randomized, Double-blind Placebo-Controlled Pharmacogenetic Study of Topiramate in European-American Heavy Drinkers — TOPG  

Alcoholism Clinical Trial

Official title: A Randomized, Double-blind Placebo-Controlled Pharmacogenetic Study of Topiramate in European-American Heavy Drinkers

Status Completed

Clinical Trial Summary

The purpose of this study is to advance the effort to develop personalized pharmacotherapy for alcohol use disorders (AUDs). The investigators propose to conduct a 12-week, prospective, randomized clinical trial of the moderating effect of rs2832407 on the efficacy of TOP in reducing heavy drinking (HD) in 200 individuals of European descent with DSM-5 AUD. The investigators will stratify the randomization on genotype and oversample rs2832407*C homozygotes, the most TOP-responsive genotype, to ensure comparable numbers of patients in the four medication x genotype groups. The investigators will use daily data collection to examine changes in relevant process variables (e.g., alcohol expectancies) and their interaction with genotype and medication group as predictors of HD. The proposed study is innovative in that it will be the first prospective test of a pharmacogenetic hypothesis involving TOP; it will use daily reports to examine expectancies and how they interact with medication and genotype to predict HD; and it will enroll DSM-5 AUD patients whose goal is either to reduce or stop drinking, which will increase the study's external validity.

Clinical Trial Description

This is a 12-week, prospective, randomized clinical trial of the moderating effect of rs2832407 on the efficacy of topiramate in reducing HD in 200 individuals of European descent with DSM-5 AUD. The investigators will stratify the randomization on genotype and oversample rs2832407*C homozygotes, the most topiramate-responsive genotype, to ensure comparable numbers of subjects in the four medication x genotype groups. The investigators will compare the efficacy of topiramate to placebo in reducing the frequency of HDDs in subjects with AUD using a two-arm, parallel-groups design. Subjects will either have a goal of reducing their drinking to safe levels or abstinence.

The investigators will use daily data collection to examine changes in relevant process variables and their interaction with genotype and medication group as predictors of HD. At each visit, all subjects will receive Medication Management (Pettinati, Weiss et al. 2004), which was developed for the COMBINE Trial and which the investigators modified to be relevant for both reducing heavy drinking and promoting abstinence. Random assignment to treatment group and double-blind conditions will be maintained throughout the study. Raters will be trained in the reliable use of all assessments. The investigators will use serum GGTP and percent disialotransferrin (%dCDT), an improved assay for carbohydrate deficient transferrin, to validate subject reports. Following a one-week pre-treatment assessment period, subjects will receive 12 weeks of treatment, after which there will be a 6-day taper period, during which subjects will reduce their dosage of topiramate gradually and then discontinue it completely. Daily reports during the treatment period will be obtained using interactive voice response (IVR) to identify subjective correlates of medication effects and to monitor medication use. Following the 12-week treatment period, subjects will be asked to return to the clinic for 3-month and 6-month post-treatment follow-up visits to evaluate the durability of treatment effects.

Two hundred men and women of European descent will be randomized to study medication. Subjects will be recruited using referrals from treatment programs throughout Philadelphia; IRB-approved advertisements on mass transit, on local radio and television stations and in newspapers, social media, and broadcast email messages at institutions that offer such a service and by posting/distributing recruitment materials in community and college settings. Respondents will initially be evaluated by telephone prior to an in-person visit to the Treatment Research Center of the University of Pennsylvania Perelman School of Medicine. The investigators will select subjects based on their genotype to ensure comparable numbers of individuals who are rs2832407*C-allele homozygotes and A-allele carriers. The investigators will block randomize subjects to balance the groups on treatment goal (i.e., reduced drinking or abstinence). ;

Related Conditions & MeSH terms

• Alcohol Use Disorder (AUD)
• Alcoholic Intoxication
• Alcoholism

• NCT number: NCT02371889
• Study type: Interventional
• Source: University of Pennsylvania
• Status: Completed
• Phase: Phase 2
• Start date: December 18, 2014
• Completion date: February 2020