Clinical trial NCT01182766: New Treatment for Alcohol and Nicotine Dependence
Official title: High and Low Dose Topiramate for the Treatment of Alcohol-Dependent Smokers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Alcohol Dependence
Nicotine Dependence
Keywords: alcohol
alcoholism
nicotine
cigarette
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: M.D. Anderson Cancer Center
name: University of California, San Diego
First posted: 2010-08-17
Enrollment: 294
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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 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 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:

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Primary outcomes:
measure: percent heavy drinking days, continuous abstinence rate for smoking
timeFrame: In the last 4 weeks of treatment
Secondary outcomes:
measure: Quality of life Questionnaire
timeFrame: In the last 4 weeks of treatment
measure: Craving for alcohol and nicotine
timeFrame: During the last 4 weeks of treatment
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Center for Addiction Research & Education
state: Virginia
city: Richmond
country: United States
facility: University of Virginia Center for Addiction Research & Education
state: Virginia
Study officials:
affiliation: University of Virginia
name: Nassima Ait-Daoud Tiouririne, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Robert M Anthenelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Paul M Cinciripini, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Bankole A Johnson, MD
role: PRINCIPAL_INVESTIGATOR
References: