Alcohol DependencePhase 2/3NCT01182766
New Treatment for Alcohol and Nicotine Dependence
A Phase 2/3 study testing Low-Dose Topiramate and High-Dose Topiramate in people with Alcohol Dependence and Nicotine Dependence, run by University of Virginia at 4 sites in United States.
Trial summary
This research study aims to test whether topiramate (a drug that is being used for seizure) will help individuals who have problems with both alcohol and nicotine. The investigators believe that individuals taking topiramate will be more successful at abstaining from both alcohol and nicotine than individuals taking… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcohol Dependence, Nicotine Dependence
- What is being tested?
- Low-Dose Topiramate and High-Dose Topiramate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 236 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Nov 2011to 6 Oct 2017
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females who have given written informed consent
- Subjects must be above the age of 18
- Good physical health
- Diagnostic and Statistical Manual (DSM)-IV diagnosis of mild to severe alcohol use disorder
- Smoking ≥ 5 cigarettes/day
- Currently drinking at least 8 standard drink units (SDUs) per week for women and at least 15 SDUs per week in the 30 days prior to randomization
Show all 10Show fewer
- Subjects must provide evidence of stable residence
- The pregnancy test for females of child-bearing potential at screen and prior to randomization must be negative. Additionally, women of child-bearing potential must be using an acceptable form of contraception.
- Literate in English and able to read, understand, and complete the rating scales and questionnaires accurately, follow instructions, and make use of the behavioral treatments
- Willing to participate in a treatment program for alcohol and nicotine dependence
Who cannot join
- Please contact site for additional information
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Virginia Center for Addiction Research & Education
Charlottesville, Virginia, 22911
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of California, San Diego
La Jolla, California, 92093
University of Virginia Center for Addiction Research & Education
Richmond, Virginia, 23294
About this study
Official title: High and Low Dose Topiramate for the Treatment of Alcohol-Dependent Smokers
This research study aims to test whether topiramate (a drug that is being used for seizure) will help individuals who have problems with both alcohol and nicotine. The investigators believe that individuals taking topiramate will be more successful at abstaining from both alcohol and nicotine than individuals taking placebo.
Read the detailed description
We propose a novel pharmacological strategy for treating alcohol and nicotine dependence concomitantly.
The reinforcing effects of both alcohol and nicotine are mediated through the cortico-mesolimbic dopamine (CMDA) system, and the concomitant use of both drugs enhances their pharmacological effects. We propose a better approach to control dopamine (DA) effects by contemporaneous indirect modulation of DA release and its functional expression. Both DA release from its cell bodies in the ventral tegmental area and the expression of its reinforcing effects through the cortico-mesolimbic system are modulated by gamma-aminobutyric acid (GABA) efferents under the tonic control of glutamate-mediated excitatory amino acid pathways. Thus, it is reasonable to hypothesize that a medication that facilitates cortico-mesolimbic GABAergic function and inhibits glutamate action should diminish both nicotine's and alcohol's reinforcing effects by inhibiting the release of midbrain DA and its functional expression through pathways projecting from the nucleus accumbens to the cortex. The promise of this novel approach is exemplified by our recent proof-of-concept demonstration that topiramate compared with placebo significantly improved smoking abstinence rates and decreased serum cotinine levels among alcohol dependent smokers. An important clinical effect of topiramate in alcohol-dependent individuals appears to be that its anti-withdrawal effects promote the gradual tapering of drinking. Hence, due to this unique anti-withdrawal effect of topiramate, we propose to adopt the same methodology for treating alcohol-dependent individuals, as is common practice with smokers, of setting a target quit date (TQD) after which relapse to either drug can be measured. We propose an 18-week, double-blind clinical trial with follow-up visits at 1 month and 3 months, in which alcohol-dependent smokers will receive brief behavioral compliance enhancement treatment (BBCET) plus a smoking self-help manual as their psychosocial treatment, and will be randomized to receive placebo,high-dose topiramate (up to 250 mg/day), or low-dose topiramate (up to 125 mg/day) to prevent relapse to heavy drinking and smoking. Each of the 3 treatment arms shall contain 98 individuals, with a total N of 294.
The TQD will occur at the beginning of the 6th week of treatment. Our primary objective is to determine whether both low- and high-dose topiramate will be more efficacious than placebo at reducing the percentage of heavy drinking days and increasing the continuous abstinence rate for smoking determined by a combination of self-report and carbon monoxide (CO) monitoring after the TQD and in the last 4 weeks of treatment. We also will be able to determine whether a lower dose of topiramate is as efficacious as the higher dose and, therefore, is associated with a lower adverse profile. Our secondary objectives are to test whether topiramate will be more efficacious than placebo at improving quality of life and reducing craving after the TQD and in the last 4 weeks of treatment and whether this improvement will be sustained in the follow-up phase.
- Conditions
- Alcohol Dependence, Nicotine Dependence
- Being tested
- Low-Dose Topiramate, Placebo, High-Dose Topiramate
- Keywords
- alcohol, alcoholism, nicotine, cigarette
- Medical subject headings
- Alcoholism, Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-Dose TopiramateDrug
Also called Topamax
Low-dose topiramate (up to 125 mg/day) with brief behavioral enhancement therapy
PlaceboDrug
Also called sugar pill
Placebo with brief behavioral enhancement therapy
High-Dose TopiramateDrug
Also called Topamax
High-dose topiramate (up to 250 mg/day) with brief behavioral enhancement therapy
| Study group | Role | What they receive |
|---|---|---|
| Low-Dose Topiramate | Experimental | Low-dose topiramate (125 mg) with brief behavioral enhancement therapy Receives: Drug: Low-Dose Topiramate |
| High-Dose Topiramate | Experimental | High-dose topiramate (250 mg) with brief behavioral enhancement therapy Receives: Drug: High-Dose Topiramate |
| Placebo | Placebo comparator | Placebo with brief behavioral enhancement therapy Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Continuous Smoking Abstinence in the Last 4 Weeks of Treatment Continuous Smoking Abstinence in the Last 4 Weeks of Treatment
No smoking in the last 4 weeks of the 18-week treatment with an expired carbon monoxide level of <10 ppm as the biochemical verification. We used the intent-to-treat assumption, where missing smoking data were considered as smoking.
Measured: Week 15 - 18 of the 18-week medication treatment
Percentage of Heavy Drinking Days (PHDD) in the Last 4 Weeks of Treatment
A heavy drinking day is defined as >= 5 standard drinking units for men and >= 4 standard drinking units for women. We calculated the PHDD used the intent-to-treat assumption, where missing drinking data were considered as heavy drinking.
Measured: Week 15 - 18 of the 18-week medication treatment
Secondary outcomes (2)
Quality of Life in the Last 4 Weeks of Treatment
We used the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) to measure quality of life in the last 4 weeks of treatment. Scoring involves summing the individual item scores on a 5-point scale, with higher scores indicating greater life satisfaction and enjoyment (better outcome). We report here a percent score of subscales contained within the Q-LES-Q, with higher scores indicating a better outcome. The subscales within the questionnaire have different numbers of items, resulting in different ranges of raw scores, so using a percent score, which used the following formula: (raw_score - scale_min_possible_score) / (scale_max_possible_score - scale_min_possible_score), helped normalize such differences, improving interpretation using the same range (i.e., 0 - 100) between subscales.
Measured: Week 15 - 18 of the 18-week medication treatment
Craving for Alcohol and Cigarettes in the Last 4 Weeks of Treatment
We used the Visual Analog Scales (VAS) to assess the craving levels for alcohol and cigarettes, respectively. VAS uses a 100 millimeter line, where 0 mm = no craving (minimum value) and 100 mm = strongest craving ever (maximum value). Participants are asked to make a mark on the line that best represents their current level of craving. Research staff then measure the distance in millimeters from the "No Craving" anchor (0 mm) to the participant's mark, which is their score. A higher score is equal to higher craving (worse outcome). Mean scores of the last 4 weeks of treatment are reported.
Measured: Week 15 - 18 of the 18-week medication treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2010 (estimated)
- Study start1 Nov 2011
- Primary completion6 Oct 2017
- Study completion6 Oct 2017
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.
- Other trials for Alcohol DependenceStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 236 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), M.D. Anderson Cancer Center, University of California, San Diego
- Responsible party
- Principal investigator, Nassima Ait-Daoud Tiouririne, University of Virginia
- Investigators
- Nassima Ait-Daoud Tiouririne, MD, Principal investigator, University of VirginiaRobert M Anthenelli, MD, Principal investigator, University of California, San DiegoPaul M Cinciripini, PHD, Principal investigator, M.D. Anderson Cancer CenterBankole A Johnson, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01182766
- Sponsor's protocol ID
- 15597
- Other IDs
- 5R01AA019720-02
- Status last verified
- Oct 2025
- First submitted
- 10 Aug 2010
- Last updated
- 31 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High and Low Dose Topiramate for the Treatment of Alcohol-Dependent Smokers
- ClinicalTrials.gov ID
- NCT01182766
- Acronym / sponsor ID
- 15597
- Conditions
- Alcohol Dependence, Nicotine Dependence
- Keywords
- alcohol, alcoholism, nicotine, cigarette
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 236 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), M.D. Anderson Cancer Center, University of California, San Diego
- Study start
- 1 Nov 2011 (actual)
- Primary completion
- 6 Oct 2017 (actual)
- Study completion
- 6 Oct 2017 (actual)
- First posted
- 17 Aug 2010 (estimated)
- Results
- Posted 31 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study aims to test whether topiramate (a drug that is being used for seizure) will help individuals who have problems with both alcohol and nicotine. The investigators believe that individuals taking topiramate will be more successful at abstaining from both alcohol and nicotine than individuals taking placebo.
Detailed description
We propose a novel pharmacological strategy for treating alcohol and nicotine dependence concomitantly.
The reinforcing effects of both alcohol and nicotine are mediated through the cortico-mesolimbic dopamine (CMDA) system, and the concomitant use of both drugs enhances their pharmacological effects. We propose a better approach to control dopamine (DA) effects by contemporaneous indirect modulation of DA release and its functional expression. Both DA release from its cell bodies in the ventral tegmental area and the expression of its reinforcing effects through the cortico-mesolimbic system are modulated by gamma-aminobutyric acid (GABA) efferents under the tonic control of glutamate-mediated excitatory amino acid pathways. Thus, it is reasonable to hypothesize that a medication that facilitates cortico-mesolimbic GABAergic function and inhibits glutamate action should diminish both nicotine's and alcohol's reinforcing effects by inhibiting the release of midbrain DA and its functional expression through pathways projecting from the nucleus accumbens to the cortex. The promise of this novel approach is exemplified by our recent proof-of-concept demonstration that topiramate compared with placebo significantly improved smoking abstinence rates and decreased serum cotinine levels among alcohol dependent smokers. An important clinical effect of topiramate in alcohol-dependent individuals appears to be that its anti-withdrawal effects promote the gradual tapering of drinking. Hence, due to this unique anti-withdrawal effect of topiramate, we propose to adopt the same methodology for treating alcohol-dependent individuals, as is common practice with smokers, of setting a target quit date (TQD) after which relapse to either drug can be measured. We propose an 18-week, double-blind clinical trial with follow-up visits at 1 month and 3 months, in which alcohol-dependent smokers will receive brief behavioral compliance enhancement treatment (BBCET) plus a smoking self-help manual as their psychosocial treatment, and will be randomized to receive placebo,high-dose topiramate (up to 250 mg/day), or low-dose topiramate (up to 125 mg/day) to prevent relapse to heavy drinking and smoking. Each of the 3 treatment arms shall contain 98 individuals, with a total N of 294.
The TQD will occur at the beginning of the 6th week of treatment. Our primary objective is to determine whether both low- and high-dose topiramate will be more efficacious than placebo at reducing the percentage of heavy drinking days and increasing the continuous abstinence rate for smoking determined by a combination of self-report and carbon monoxide (CO) monitoring after the TQD and in the last 4 weeks of treatment. We also will be able to determine whether a lower dose of topiramate is as efficacious as the higher dose and, therefore, is associated with a lower adverse profile. Our secondary objectives are to test whether topiramate will be more efficacious than placebo at improving quality of life and reducing craving after the TQD and in the last 4 weeks of treatment and whether this improvement will be sustained in the follow-up phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low-Dose Topiramate | Experimental | Drug: Low-Dose TopiramateLow-dose topiramate (125 mg) with brief behavioral enhancement therapy |
| High-Dose Topiramate | Experimental | Drug: High-Dose TopiramateHigh-dose topiramate (250 mg) with brief behavioral enhancement therapy |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo with brief behavioral enhancement therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Males and females who have given written informed consent
- Subjects must be above the age of 18
- Good physical health
- Diagnostic and Statistical Manual (DSM)-IV diagnosis of mild to severe alcohol use disorder
- Smoking ≥ 5 cigarettes/day
Key exclusion criteria (1 listed)
- Please contact site for additional information
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 |
|---|---|---|
| Low-Dose TopiramateAlso: TopamaxLow-dose topiramate (up to 125 mg/day) with brief behavioral enhancement therapy | Drug | Low-Dose Topiramate |
| PlaceboAlso: sugar pillPlacebo with brief behavioral enhancement therapy | Drug | Placebo |
| High-Dose TopiramateAlso: TopamaxHigh-dose topiramate (up to 250 mg/day) with brief behavioral enhancement therapy | Drug | High-Dose Topiramate |
Primary outcome
Continuous Smoking Abstinence in the Last 4 Weeks of Treatment Continuous Smoking Abstinence in the Last 4 Weeks of Treatment
Time frame: Week 15 - 18 of the 18-week medication treatment
No smoking in the last 4 weeks of the 18-week treatment with an expired carbon monoxide level of <10 ppm as the biochemical verification. We used the intent-to-treat assumption, where missing smoking data were considered as smoking.
Percentage of Heavy Drinking Days (PHDD) in the Last 4 Weeks of Treatment
Time frame: Week 15 - 18 of the 18-week medication treatment
A heavy drinking day is defined as >= 5 standard drinking units for men and >= 4 standard drinking units for women. We calculated the PHDD used the intent-to-treat assumption, where missing drinking data were considered as heavy drinking.
2 secondary outcomes
Quality of Life in the Last 4 Weeks of Treatment
Time frame: Week 15 - 18 of the 18-week medication treatment
Craving for Alcohol and Cigarettes in the Last 4 Weeks of Treatment
Time frame: Week 15 - 18 of the 18-week medication treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- (UVA CARE Website)Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Alcohol Dependence
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingPhase 1
Environment and Alcohol: A Pilot Study
Alcohol Use Disorder
RecruitingObservational study
SMART-r: Substance Monitoring and Active Relapse Tracking Repository
Alcoholism, Substance-Related Disorders
Not yet recruiting
A MRT to Optimize a JITAI for Alcohol Craving and Suicide Ideation
Alcohol Use Disorder (AUD), Suicide Ideation
RecruitingPhase 2
Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder
Alcohol Use Disorder
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.
Nassima Ait-Daoud Tiouririne, MD principal investigator
University of Virginia
Robert M Anthenelli, MD principal investigator
University of California, San Diego
Paul M Cinciripini, PHD principal investigator
M.D. Anderson Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Low-Dose Topiramate and High-Dose Topiramate in people with Alcohol Dependence and Nicotine Dependence, run by University of Virginia at 4 sites 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 10 inclusion and 1 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 31 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 31 Oct 2025). 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?
Continuous Smoking Abstinence in the Last 4 Weeks of Treatment Continuous Smoking Abstinence in the Last 4 Weeks of Treatment (time frame: Week 15 - 18 of the 18-week medication treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2025.