Official Title: “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 Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: May 2012

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 effects of topiramate in vitro using neural cultures generated from skin biopsies obtained from study participants (participation in the substudy is completely optional). Specifically, we will 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(s) in this Clinical Trial

• Drug: topiramate
  • 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)
• Drug: placebo
  • 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)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • topiramate (up to 200 mg orally)
• Placebo Comparator: 2
  • placebo

Primary Measures

• drinking days and heavy drinking days
  • Time Frame: 12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment
    Safety Issue?: No

Secondary Measures

• mean daily alcohol consumption
  • Time Frame: 12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment
    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
    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
    Safety Issue?: No

Inclusion Criteria:

• age 18 to 65 years, inclusive;
• have an average weekly ethanol consumption of >=24 standard drinks for men, or >=18 standard drinks for women;
• be able to read English at the 8th grade or higher level and show no evidence of significant cognitive impairment;
• be willing to nominate an individual who will know the patient's whereabouts in order to facilitate follow up during the study;
• if a woman of child-bearing potential (i.e., who has not had a hysterectomy, bilateral oophorectomy, tubal ligation or who are less than two years postmenopausal), must be non-lactating, practicing a reliable method of birth control, and have a negative serum pregnancy test prior to initiation of treatment;
• if applicable, individuals being treated with a single antidepressant that has been stable in dosage for a minimum of four weeks; and
• be willing to provide signed, informed consent to participate in the study (including a willingness to reduce drinking to non-hazardous levels).

Exclusion Criteria:

• a current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation, including direct bilirubin elevations of >110% or transaminase elevations >300% normal (We will not exclude patients with hypertension, diabetes mellitus, asthma or other common medical conditions, as long as these are adequately controlled and the patient has an ongoing relationship with a primary-care practitioner);
• a history of nephrolithiasis;
• a history of glaucoma;
• a serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or psychotic major depression, panic disorder, borderline or antisocial personality disorder, organic mood or mental disorders, eating disorder, or substantial suicide or violence risk) on the basis of history or psychiatric examination;
• a current Diagnostic & Statistical Manual of Mental Disorders 4th ed (DSM-IV) diagnosis of drug dependence (other than nicotine dependence);
• a current Diagnostic and Statistical Manual of Mental Disorders 4th ed (DSM-IV) diagnosis of alcohol dependence that is clinically moderate or severe;
• a history of hypersensitivity to topiramate;
• currently taking any tricyclic antidepressant (e.g., Adapin (doxepin), Anafranil (clomipramine), Elavil (amitryptyline), Pamelor (nortryptyline), Tofranil (imipramine), Sinequan (doxepin); or
• are considered by the investigators to be an unsuitable candidate for receipt of an investigational drug.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Connecticut Health Center

Overall Clinical Trial Officials and Contacts

Henry R Kranzler, M.D. Principal Investigator University of Connecticut Health Center  

Overall Contact: Kristen A Tremblay, MPH 860-679-4755 tremblay@psychiatry.uchc.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00626925

Study ID Number: 08-052-2

ClinicalTrials.gov Identifier: NCT00626925

Health Authority: United States: Institutional Review Board