Back to resultsTopiramate Treatment of Problem Drinkers
Primary Purpose
Alcohol Drinking
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
topiramate
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Alcohol Drinking focused on measuring Randomized Trial, Medication for Heavy Drinking, Topiramate Treatment
Eligibility Criteria
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.
Sites / Locations
- University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Total Topiramate Group
Total Placebo Group
Arm Description
topiramate capsules beginning at 25 mg/day with gradual increase to a maximum of 200 mg orally)
inactive placebo matched in appearance with topiramate capsules
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Mean Abstinent Days Per Week by Medication Group
Mean Daily Alcohol Consumption
Mean Heavy Drinking Days Per Week by Medication Group and rs2832407 Genotype
Mean Abstinent Days Per Week by Medication Group and rs2832407 Genotype
Severity of Alcohol-related Problems at End of Treatment
The Short Inventory of Problems (SIP). The SIP, a 15-item instrument, yields a total score that ranges from 0 to 45, higher score indicating higher levels of drinking problems. The SIP was derived from the Drinker Inventory of Consequences (DrInC), which was developed for use in Project MATCH (Miller and Tonigan 1995). We (Feinn et al. 2003) have found that, like the DrInC, the SIP measures a single factor of alcohol-related problems. Given that it is substantially shorter than the DrInC, we will use the SIP as a measure of alcohol-related consequences.
Gamma-glutamyl Transferase (GGT) at Midpoint
Gamma-glutamyl transferase (GGT) is a liver enzyme biochemical measure used to detect liver health and function and alcohol consumption. GGT is a very sensitive measure than can change very quickly compared to other biochemical markers.
Gamma-glutamyl Transferase (GGT) at End of Treatment
Gamma-glutamyl transferase (GGT) is a liver enzyme biochemical measure used to detect liver health and function and alcohol consumption. GGT is a very sensitive measure than can change very quickly compared to other biochemical markers.
Full Information
NCT ID
NCT00626925
First Posted
February 21, 2008
Last Updated
February 7, 2018
Sponsor
UConn Health
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT00626925
Brief Title
Topiramate Treatment of Problem Drinkers
Official Title
Topiramate Treatment of Problem Drinkers
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UConn Health
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Drinking
Keywords
Randomized Trial, Medication for Heavy Drinking, Topiramate Treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
200 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Total Topiramate Group
Arm Type
Active Comparator
Arm Description
topiramate capsules beginning at 25 mg/day with gradual increase to a maximum of 200 mg orally)
Arm Title
Total Placebo Group
Arm Type
Placebo Comparator
Arm Description
inactive placebo matched in appearance with topiramate capsules
Intervention Type
Drug
Intervention Name(s)
topiramate
Other Intervention Name(s)
Topamax
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
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)
Primary Outcome Measure Information:
Title
Mean Heavy Drinking Days Per Week by Medication Group
Description
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.
Time Frame
12 weeks (from initiation to end of treatment)
Secondary Outcome Measure Information:
Title
Mean Abstinent Days Per Week by Medication Group
Time Frame
12 weeks
Title
Mean Daily Alcohol Consumption
Time Frame
12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment
Title
Mean Heavy Drinking Days Per Week by Medication Group and rs2832407 Genotype
Time Frame
12 weeks
Title
Mean Abstinent Days Per Week by Medication Group and rs2832407 Genotype
Time Frame
12 weeks
Title
Severity of Alcohol-related Problems at End of Treatment
Description
The Short Inventory of Problems (SIP). The SIP, a 15-item instrument, yields a total score that ranges from 0 to 45, higher score indicating higher levels of drinking problems. The SIP was derived from the Drinker Inventory of Consequences (DrInC), which was developed for use in Project MATCH (Miller and Tonigan 1995). We (Feinn et al. 2003) have found that, like the DrInC, the SIP measures a single factor of alcohol-related problems. Given that it is substantially shorter than the DrInC, we will use the SIP as a measure of alcohol-related consequences.
Time Frame
12 weeks (from intiation to end of treatment)
Title
Gamma-glutamyl Transferase (GGT) at Midpoint
Description
Gamma-glutamyl transferase (GGT) is a liver enzyme biochemical measure used to detect liver health and function and alcohol consumption. GGT is a very sensitive measure than can change very quickly compared to other biochemical markers.
Time Frame
6 weeks (from initiation to midpoint)
Title
Gamma-glutamyl Transferase (GGT) at End of Treatment
Description
Gamma-glutamyl transferase (GGT) is a liver enzyme biochemical measure used to detect liver health and function and alcohol consumption. GGT is a very sensitive measure than can change very quickly compared to other biochemical markers.
Time Frame
12 weeks (from initiation to end of treatment)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henry R Kranzler, M.D.
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35229945
Citation
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.
Results Reference
derived
PubMed Identifier
34049101
Citation
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.
Results Reference
derived
PubMed Identifier
26891181
Citation
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.
Results Reference
derived
PubMed Identifier
24786948
Citation
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.
Results Reference
derived
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Topiramate Treatment of Problem Drinkers
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