New Treatment for Alcohol and Nicotine Dependence

May 6, 2022 updated by: Nassima Ait-Daoud Tiouririne, University of Virginia

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 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 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 Type

Interventional

Enrollment (Anticipated)

294

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • University of California, San Diego
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Virginia
      • Charlottesville, Virginia, United States, 22911
        • University of Virginia Center for Addiction Research & Education
      • Richmond, Virginia, United States, 23294
        • University of Virginia Center for Addiction Research & Education

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and females who have given written informed consent
  • Subjects must be above the age of 18
  • Good physical health
  • 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
  • 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

Exclusion Criteria:

Please contact site for additional information

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: topiramate
topiramate with brief behavioral enhancement therapy
Drug: Topiramate with brief behavioral enhancement therapy
high-dose topiramate (up to 250 mg/day), or low-dose topiramate (up to 125 mg/day)
Other Names:
  • Topamax
Placebo Comparator: Placebo
Placebo with brief behavioral enhancement therapy
Drug: Placebo with brief behavioral enhancement therapy
placebo
Other Names:
  • sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
percent heavy drinking days, continuous abstinence rate for smoking
Time Frame: In the last 4 weeks of treatment
The timeline follow-back (TLFB) method of measuring alcohol consumption will be used for PHDD.Continuous abstinence in smoking is determined by a combination of self-report and CO monitoring after the quit date
In the last 4 weeks of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life Questionnaire
Time Frame: In the last 4 weeks of treatment
Quality of life will be assessed using The Quality of Life Enjoyment and Satisfaction Questionnaire
In the last 4 weeks of treatment
Craving for alcohol and nicotine
Time Frame: During the last 4 weeks of treatment
alcohol and nicotine craving scales will be used to monitor craving
During the last 4 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Virginia

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
M.D. Anderson Cancer Center
University of California, San Diego

Investigators

  • Principal Investigator: Nassima Ait-Daoud Tiouririne, MD, University of Virginia
  • Principal Investigator: Robert M Anthenelli, MD, University of California, San Diego
  • Principal Investigator: Paul M Cinciripini, PhD, M.D. Anderson Cancer Center
  • Principal Investigator: Bankole A Johnson, MD, University of Virginia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Anticipated)

June 1, 2022

Study Completion (Anticipated)

June 1, 2022

Study Registration Dates

First Submitted

August 10, 2010

First Submitted That Met QC Criteria

August 16, 2010

First Posted (Estimate)

August 17, 2010

Study Record Updates

Last Update Posted (Actual)

May 9, 2022

Last Update Submitted That Met QC Criteria

May 6, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15597
  • 5R01AA019720-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Alcohol Dependence

Clinical Trials on Topiramate with brief behavioral enhancement therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Norway

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe