Alcohol DrinkingPhase 4NCT00626925
Topiramate Treatment of Problem Drinkers
A Phase 4 study testing topiramate in people with Alcohol Drinking, run by UConn Health at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Alcohol Drinking
- What is being tested?
- topiramate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2008to Nov 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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;
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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.
Read the 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.
- Conditions
- Alcohol Drinking
- Being tested
- topiramate, placebo
- Keywords
- Randomized Trial, Medication for Heavy Drinking, Topiramate Treatment
- Medical subject headings
- Alcohol Drinking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
topiramateDrug
Also called Topamax
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)
placeboDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Total Topiramate Group | Active comparator | topiramate capsules beginning at 25 mg/day with gradual increase to a maximum of 200 mg orally) Receives: Drug: topiramate |
| Total Placebo Group | Placebo comparator | inactive placebo matched in appearance with topiramate capsules Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks (from initiation to end of treatment)
Secondary outcomes (7)
Mean Abstinent Days Per Week by Medication Group
Measured: 12 weeks
Mean Daily Alcohol Consumption
Measured: 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
Measured: 12 weeks
Mean Abstinent Days Per Week by Medication Group and rs2832407 Genotype
Measured: 12 weeks
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.
Measured: 12 weeks (from intiation to end of treatment)
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.
Measured: 6 weeks (from initiation to midpoint)
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.
Measured: 12 weeks (from initiation to end of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2008 (estimated)
- Study startFeb 2008
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Alcohol DrinkingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Henry Kranzler, UConn Health
- Investigators
- Henry R Kranzler, M.D., Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00626925
- Sponsor's protocol ID
- 08-052-2
- Other IDs
- P60AA003510, M01RR006192
- Status last verified
- Feb 2018
- First submitted
- 21 Feb 2008
- Last updated
- 8 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Kranzler HR, Jinwala Z, Davis CN, Xu H, Biernacka JM, Zhou H, Kember RL, Gelernter J, Feinn R. Moderation of treatment outcomes by polygenic risk for alcohol-related traits in placebo-controlled trials of topiramate. Alcohol Clin Exp Res (Hoboken). 2025 Jun;49(6):1297-1305. doi: 10.1111/acer.70052. Epub 2025 May 30.
PubMed 40445294Kranzler 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.
PubMed 35229945Kranzler 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.
PubMed 34049101Feinn 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.
PubMed 26891181Kranzler 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.
PubMed 24786948
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topiramate Treatment of Problem Drinkers
- ClinicalTrials.gov ID
- NCT00626925
- Acronym / sponsor ID
- 08-052-2
- Conditions
- Alcohol Drinking
- Keywords
- Randomized Trial, Medication for Heavy Drinking, Topiramate Treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Center for Research Resources (NCRR)
- Study start
- Feb 2008
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 29 Feb 2008 (estimated)
- Results
- Posted 3 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Total Topiramate Group | Active comparator | Drug: topiramatetopiramate capsules beginning at 25 mg/day with gradual increase to a maximum of 200 mg orally) |
| Total Placebo Group | Placebo comparator | Drug: placeboinactive placebo matched in appearance with topiramate capsules |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (9 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| topiramateAlso: Topamaxup 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 | Total Topiramate Group |
| placeboplacebo (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) | Drug | Total Placebo Group |
Primary outcome
Mean Heavy Drinking Days Per Week by Medication Group
Time frame: 12 weeks (from initiation to end of treatment)
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.
7 secondary outcomes
Mean Abstinent Days Per Week by Medication Group
Time frame: 12 weeks
Mean Daily Alcohol Consumption
Time frame: 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
Time frame: 12 weeks
Mean Abstinent Days Per Week by Medication Group and rs2832407 Genotype
Time frame: 12 weeks
Severity of Alcohol-related Problems at End of Treatment
Time frame: 12 weeks (from intiation to end of treatment)
Gamma-glutamyl Transferase (GGT) at Midpoint
Time frame: 6 weeks (from initiation to midpoint)
Gamma-glutamyl Transferase (GGT) at End of Treatment
Time frame: 12 weeks (from initiation to end of treatment)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40445294Kranzler HR, Jinwala Z, Davis CN, Xu H, Biernacka JM, Zhou H, Kember RL, Gelernter J, Feinn R. Moderation of treatment outcomes by polygenic risk for alcohol-related traits in placebo-controlled trials of topiramate. Alcohol Clin Exp Res (Hoboken). 2025 Jun;49(6):1297-1305. doi: 10.1111/acer.70052. Epub 2025 May 30.
- Derived from this study: PubMed 35229945Kranzler 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.
- Derived from this study: PubMed 34049101Kranzler 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.
- Derived from this study: PubMed 26891181Feinn 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.
- Derived from this study: PubMed 24786948Kranzler 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henry R Kranzler, M.D. principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing topiramate in people with Alcohol Drinking, run by UConn Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Heavy Drinking Days Per Week by Medication Group (time frame: 12 weeks (from initiation to end of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00626925, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2018.