New Treatment for Alcohol and Nicotine Dependence

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Virginia
Sponsor:
Collaborators:
M.D. Anderson Cancer Center
University of California, San Diego
Information provided by (Responsible Party):
Nassima Ait-Daoud Tiouririne, University of Virginia
ClinicalTrials.gov Identifier:
NCT01182766
First received: August 10, 2010
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Alcohol Dependence
Nicotine Dependence
Drug: Topiramate with brief behavioral enhancement therapy
Drug: Placebo with brief behavioral enhancement therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: High and Low Dose Topiramate for the Treatment of Alcohol-Dependent Smokers

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • percent heavy drinking days, continuous abstinence rate for smoking [ Time Frame: In the last 4 weeks of treatment ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Quality of life [ Time Frame: In the last 4 weeks of treatment ] [ Designated as safety issue: No ]
    Quality of life will be assessed using The Quality of Life Enjoyment and Satisfaction Questionnaire

  • Craving for alcohol and nicotine [ Time Frame: During the last 4 weeks of treatment ] [ Designated as safety issue: No ]
    alcohol and nicotine craving scales will be used to monitor craving


Estimated Enrollment: 294
Study Start Date: September 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Topamax
Placebo Comparator: Placebo
Placebo with brief behavioral enhancement therapy
Drug: Placebo with brief behavioral enhancement therapy
placebo
Other Name: sugar pill

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01182766

Contacts
Contact: Eva Jenkins-Mendoza 1-888-882-2345 emj9c@virginia.edu

Locations
United States, California
University of California, San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Nicole M Bekman, Ph.D.    858-534-9456    nbekman@ucsd.edu   
Principal Investigator: Robert M Anthenelli, MD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: O'Neak Henigan    713-745-4472    OCHenigan@manderson.org   
Principal Investigator: Paul M Cinciripini, Ph.D.         
United States, Virginia
University of Virginia Center for Addiction Research & Education Recruiting
Charlottesville, Virginia, United States, 22911
Contact: Eva Jenkins-Mendoza    888-882-2345    emj9c@virginia.edu   
Principal Investigator: Nassima Ait-Daoud Tiouririne, MD         
University of Virginia Center for Addiction Research & Education Active, not recruiting
Richmond, Virginia, United States, 23294
Sponsors and Collaborators
University of Virginia
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
  More Information

Additional Information:
No publications provided

Responsible Party: Nassima Ait-Daoud Tiouririne, Associate Professor, Director of UVA Center for Addiction Research and Education, University of Virginia
ClinicalTrials.gov Identifier: NCT01182766     History of Changes
Other Study ID Numbers: 15597, 5R01AA019720-02
Study First Received: August 10, 2010
Last Updated: June 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
alcohol
alcoholism
nicotine
cigarette

Additional relevant MeSH terms:
Alcoholism
Tobacco Use Disorder
Alcohol-Related Disorders
Substance-Related Disorders
Mental Disorders
Topiramate
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents

ClinicalTrials.gov processed this record on July 20, 2014