Topiramate Treatment of Problem Drinkers

NCT00626925 | Completed Phase 4 Results

• 3 other identifiers: 08-052-2P60AA003510M01RR006192
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alcohol Drinking

Keywords

Randomized Trial; Medication for Heavy Drinking; Topiramate Treatment

Outcome Measures

Primary Outcomes (1)

• Mean Heavy Drinking Days Per Week by Medication Group

  Change in the number of heavy drinking days during treatment phase of study. Drinking data were aggregated to the weekly level. The number of days per week of heavy drinking (i.e., four or more drinks in a day for women and five or more drinks in a day for men) and of abstinence were the primary outcomes.

  12 weeks (from initiation to end of treatment)

Secondary Outcomes (7)

• Mean Abstinent Days Per Week by Medication Group

  12 weeks

• Mean Daily Alcohol Consumption

  12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment

• Mean Heavy Drinking Days Per Week by Medication Group and rs2832407 Genotype

  12 weeks

• Mean Abstinent Days Per Week by Medication Group and rs2832407 Genotype

  12 weeks

• Severity of Alcohol-related Problems at End of Treatment

  12 weeks (from intiation to end of treatment)

Study Arms (2)

Total Topiramate Group

ACTIVE COMPARATOR

topiramate capsules beginning at 25 mg/day with gradual increase to a maximum of 200 mg orally)

Drug: topiramate

Total Placebo Group

PLACEBO COMPARATOR

inactive placebo matched in appearance with topiramate capsules

Drug: placebo

Interventions

topiramate DRUG

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)

Also known as: Topamax

Total Topiramate Group

placebo DRUG

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)

Total Placebo Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• UConn Health: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (4)

• Kranzler HR, Feinn R, Pond T, Hartwell E, Gelernter J, Crist RC, Witkiewitz K. Post-treatment effects of topiramate on alcohol-related outcomes: A combined analysis of two placebo-controlled trials. Addict Biol. 2022 Mar;27(2):e13130. doi: 10.1111/adb.13130.

  PMID: 35229945 DERIVED

• Kranzler HR, Hartwell EE, Feinn R, Pond T, Witkiewitz K, Gelernter J, Crist RC. Combined analysis of the moderating effect of a GRIK1 polymorphism on the effects of topiramate for treating alcohol use disorder. Drug Alcohol Depend. 2021 Aug 1;225:108762. doi: 10.1016/j.drugalcdep.2021.108762. Epub 2021 May 21.

  PMID: 34049101 DERIVED

• Feinn R, Curtis B, Kranzler HR. Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care. J Clin Psychiatry. 2016 Mar;77(3):e278-82. doi: 10.4088/JCP.15m10053.

  PMID: 26891181 DERIVED

• Kranzler HR, Armeli S, Feinn R, Tennen H, Gelernter J, Covault J. GRIK1 genotype moderates topiramate's effects on daily drinking level, expectations of alcohol's positive effects and desire to drink. Int J Neuropsychopharmacol. 2014 Oct;17(10):1549-56. doi: 10.1017/S1461145714000510. Epub 2014 Apr 30.

  PMID: 24786948 DERIVED

MeSH Terms

Conditions

Alcohol Drinking

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Drinking Behavior; Behavior

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Henry R. Kranzler, M.D.
• Organization: University of Pennsylvania Perelman School of Medicine

kranzler@mail.med.upenn.edu

215-386-6662

Study Officials

• Henry R Kranzler, M.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: February 21, 2008
• First Posted: February 29, 2008
• Study Start: February 1, 2008
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: March 8, 2018
• Results First Posted: August 3, 2016

Record last verified: 2018-02

Locations

US (1)