Topiramate Treatment of Problem Drinkers
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Topiramate Treatment of Problem Drinkers|
- drinking days and heavy drinking days [ Time Frame: 12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment ] [ Designated as safety issue: No ]
- mean daily alcohol consumption [ Time Frame: 12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment ] [ Designated as safety issue: No ]
- change in gamma-glutamyl transferase (GGT) or carbohydrate-deficient transferrin (CDT) levels [ Time Frame: 12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment ] [ Designated as safety issue: No ]
- severity of alcohol-related problems (as measured on the Short Inventory of Problems; SIP) [ Time Frame: 12 weeks (from intiation to end of treatment); 3- and 6-months post-treatment ] [ Designated as safety issue: No ]
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||November 2013|
|Estimated Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
topiramate (up to 200 mg orally)
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)
Other Name: Topamax
Placebo Comparator: 2
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)
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.
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Henry R Kranzler, M.D.||University of Pennsylvania|