Topiramate Treatment of Problem Drinkers
Condition: Alcohol Drinking
MeSH terms: Alcohol Drinking
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to evaluate the safety and efficacy of topiramate in reducing
      drinking and heavy drinking frequency in problem drinkers. We hypothesize that at a dosage of
      up to 200mg/day, topiramate will be well tolerated in this patient population and that,
      compared to placebo treatment, topiramate will result in a greater reduction in the frequency
      of both drinking days and heavy drinking days.
    

Detailed description: 
      It is estimated that 30% of the general population are problem drinkers (NIAAA 2007). Despite
      its high prevalence, problem drinkers are understudied, particularly with respect to
      medications that may help them to reduce their drinking to safe levels. The study will extend
      to this patient population findings from a trial of topiramate, which showed the drug to be
      well tolerated and efficacious in moderately-severe alcohol-dependent patients (Johnson et
      al. 2003).

      This is a 13-week, double-blind, placebo-controlled study of topiramate (12 weeks during
      which the dosage of study medication is gradually increased up to 200 mg orally and then
      maintained, and 1 week of medication taper) and medical management counseling to reduce
      drinking among problem drinkers (i.e., heavy drinkers without evidence of physical dependence
      on alcohol) who want to reduce their drinking.

      Participants attend weekly study visits for the first 5 weeks and then bi-weekly visits for
      the last 8 weeks of the study, and are randomly assigned to receive topiramate or placebo on
      a daily basis. In addition to study visits, participants report daily moods, drinking, and
      medication usage through an Interactive Voice Response (IVR) system they call each night.
      In-person follow-up evaluations are conducted at 3 and 6 months post-treatment to provide a
      measure of the durability of treatment effects. This study also aims to examine the relation
      between genotype and the response to topiramate treatment.

      An additional aim is to conduct a substudy to examine neural cells generated from skin
      fibroblast cells obtained from study participants via a skin biopsy (participation in the
      substudy is completely optional). Initially, we will examine variables key to reliably
      generating neurons from the cells and characterize these neurons using a variety of
      laboratory measures. A longer term goal is to compare gene expression in individuals who show
      a robust reduction in drinking following treatment with topiramate with those who show no
      beneficial treatment effects.

      A second additional aim is to explore whether the therapeutic and adverse effects of
      topiramate are similar in patients on a stable regimen of an antidepressant to those not
      receiving such therapy. Although exploratory, given the absence of data that directly address
      this issue, we will stratify subjects by the presence or absence of current antidepressant
      therapy.

      Careful evaluation of the study's hypotheses will provide important information on the
      efficacy and mechanism of effects of topiramate as a treatment for problem drinkers.
    

Intervention name(s): topiramate; placebo
Intervention type(s): Drug; Drug
Intervention description(s): up to 200mg/day orally (over 12 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper); placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)
Other intervention name(s): Topamax
Intervention MeSH terms: Topiramate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Randomized Trial; Medication for Heavy Drinking; Topiramate Treatment