The Effects of Topiramate on Alcohol Use in Alcohol Dependent Subjects

Phase 4

Completed

Conditions: Alcoholism

Interventions: Drug: Topiramate (Topamax)

Registration Number: NCT00329407

Lead Sponsor: Boston University

Brief Summary: This investigation will assess the effectiveness of topiramate in reducing ethanol consumption by alcohol dependent subjects. It also will seek to establish whether topiramate can be safely used in this population including whether it might be subject to abuse by alcohol dependent individuals.

A secondary goal of this study is to assess the effects of topiramate on verbal fluency during treatment for alcohol dependence.

Detailed Description: Alcoholism is a disorder that produces extensive morbidity and mortality. Substantial progress has been made in the development of medications that can help to promote abstinence in alcohol dependent individuals. However, investigations of the most promising drugs, particularly naltrexone and acamprosate, suggest that these agents have at best moderate efficacy and there is a great need for additional medications for the treatment of alcoholism.

The results of a recent study suggest that the administration of the anticonvulsant agent ,topiramate helps alcoholic individuals to maintain abstinence (Johnson et al., 2003). The objectives of this study is to determine whether topiramate will reduce the consumption of alcohol in subjects dependent on this substance, as has been previously reported.Other study objectives are to assess the abuse liability properties of topiramate in alcohol dependent subjects and to examine the effects of chronic topiramate administration on cognitive functioning.

This will be a thirteen week long open label clinical trial of the effects of topiramate administration on ethanol consumption by alcohol dependent subjects.

Subjects will be asked to provide informed consent and then will be screened on the same day to determine if they meet study eligibility criteria. Subjects will be asked to return to provide two urines over the following week.

Baseline measures of mood, craving, withdrawal, cognitive functioning and physical health will be obtained. In the afternoon they will receive their first dose of medication. Their responses to this medication challenge will be assessed over a 3-hour period.

During the drug treatment phase subjects will be asked to come to the clinic weekly for assessment and manual guided therapy during weeks 1-4 and biweekly during weeks 6-8. On day 85 subjects will be seen at the clinic for a termination visit.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

DSM-IV Diagnosis of Alcohol Dependence; Minimal drinking level of 14 drinks per week for women and 20 drinks per week for men over a consecutive 30 day period during the last 90 days
Intent to stop drinking
Male or female age 18-65
Able to maintain sobriety for 3 consecutive days without the use of detoxification medications
Able to provide informed consent and to comprehend study procedures.
If a woman, then is willing to use an effective means of birth control during throughout the study period. These include: a. barrier (diaphragm or condom) with spermicide b.intrauterine progesterone contraceptive system c. levonorgestrel implant d. medroxyprogesterone acetate contraceptive injection e. complete abstinence

Exclusion Criteria

Dependent on or extensive abuse of drugs or substances other than ethanol, nicotine, or caffeine as assessed by urine toxicology (2 out of 3 Dependent on or extensive abuse of drugs or substances other than positive consecutive urines)
DSM IV Axis I diagnoses other than ethanol, caffeine, or nicotine dependence severe enough to require treatment with medication or to prevent compliance with the protocol.
Currently being treated with disulfiram (Antabuse), naltrexone (ReVia), or acamprosate
Currently being treated with any other psychoactive or other CNS medications or a carbonic anhydrase inhibitor (e.g. acetazolamide)
In need of medical detoxification from alcohol.
Prior history of kidney stones.
History of liver disease. ALT or AST 3 times higher than upper range of normal values.
BUN or serum creatinine outside the normal range
Major neurological disorder including seizures
Other major diseases including severe hypertension, renal disease, or cardiac disease.
Prior participation within 60 days in another clinical study.
If female, a positive serum HCG or breast feeding.
If female using oral contraceptives as a means of birth control.
History of allergic sensitivity to topiramate
Pending imprisonment
Cardiac pacemaker or metal surgical implant.
History of angle closure glaucoma.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Topiramate Treatment	Topiramate (Topamax)	In this open label non-placebo controlled trial all subjects received topiramate, the active medication. Medication Dosing Schedule: Days 1-3 50 mg q PM Days 4-7 50 mg BID Days 8-11 50 mg q AM \& 100 mg q PM Days 12-15 100mg BID Days 16-19 100 mg q AM \& 150 mg q PM Days 20-23 150 mg BID Days 24-27 150 mg qAM \& 200 mg q PM Days 28-70 200 mg BID Days 71-77 150 mg BID Days 78-84 100mg BID Days 85-87 50 mg BID Days 88-91 50 mg qPM

Primary Outcome Measures

Name	Time	Method
The Primary Outcome Measure Will be Subjects Ethanol Consumption Over the Course of the Drug Treatment Period as Assessed by the Timeline Followback Method	70 days	The primary outcome was the mean daily consumption of standard alcoholic drinks (14 g per ethanol) during the baseline week compared to week 10, the final week subjects were one maintenance dose of topirmate.

Secondary Outcome Measures

Name	Time	Method
Phonetic Portion of the Controlled Word Association Test (COWAT)	Baseline compared to Week 10	Phonetic COWAT is a measure of verbal fluency. Results are in terms of number of words produced starting with a set of particular letters.This involves a comparison of baseline and Week 10 COWAT scores