Alcohol Dependence, Nicotine Dependence
Conditions
Keywords
tobacco use disorders, alcoholism
Brief summary
The purpose of this study is to determine whether topiramate is effective as an aid to smoking cessation for recovering alcohol dependent men.
Detailed description
This study is a 12-week, double-blind, placebo-controlled trial to test the efficacy of topiramate versus placebo as an aid to smoking cessation for recovering alcohol dependent men. Another aim of the study is to explore whether or not topiramate reduces relapse to alcohol use in patients with comorbid alcohol and nicotine dependence. All participants will receive a standardized psychosocial intervention in combination with the medication (or placebo). Following completion of the treatment phase of the study, participants will enter a 24-week follow-up period during which the longer-term outcome of the intervention will be assessed.
Interventions
DRUGTopiramate
Topiramate will be titrated over 5 weeks to a maximum dosage of 200 mg according to the following schedule: 25mg daily for days 1-7, 50mg daily for days 8-14, 75mg daily for days 15-21, 100mg daily for days 22-28, 150mg daily for days 29-35, 200mg daily for days 36-42. Maximum dosage will be maintained for 6 weeks, followed by a one-week taper-off period (100mg daily for 4 days and 50mg daily for 3 days).
DRUGPlacebo
Placebo/study medication will be administered in opaque capsules in an identical fashion to maintain the double-blind study design.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Subjects will be included if they: * are 18-70 years of age, inclusive; * are male outpatients with a diagnosis of DSM-IV-TR nicotine dependence and alcohol dependence in early full remission (1-36 months abstinence); * are current tobacco smokers who smoke an average of 10 or more cigarettes per day in the two months prior to the screening visit; * are motivated to try to quit smoking and maintain abstinence from alcohol and other illicit drugs;
Exclusion criteria
Subjects will be excluded if they: * have any clinically significant laboratory evidence of hematologic, hepatic, cardiovascular, renal, pulmonary, or thyroid disease; * have a current significant neurologic, hepatic, renal, gastrointestinal, pulmonary, metabolic, cardiovascular, infectious, or endocrine disease; * have a history of known hypersensitivity to topiramate; * in the investigator's judgment, pose a current suicidal or homicidal risk; * have taken any investigational drug within 30 days of baseline; and * have a current seizure disorder or a history of severe alcohol withdrawal (alcohol withdrawal seizures, hallucinations / illusions, delirium tremens).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 4-week Continuous Abstinence From Smoking | Weeks 8-12 of treatment. | This measure indicates the proportion of participants who did or did not smoke any cigarettes during the final 4 weeks of treatment, which represented weeks 8-12 of study participation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Relapsing to Any Drinking or Illicit Drug Use | 12-week treatment phase, 36-week combined treatment and follow-up | Alcohol or illicit drug use during treatment or follow up. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Received active topiramate | 63 |
| Placebo Received placebo | 66 |
| Total | 129 |
Baseline characteristics
| Characteristic | Topiramate | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 9 | 46.9 years STANDARD_DEVIATION 9.8 | 47.0 years STANDARD_DEVIATION 9.4 |
| Fagerstrom | 5.4 units on a scale STANDARD_DEVIATION 2 | 6.1 units on a scale STANDARD_DEVIATION 1.6 | 5.8 units on a scale STANDARD_DEVIATION 1.7 |
| Gender Female | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 63 Participants | 66 Participants | 129 Participants |
| Race/Ethnicity, Customized Caucasian | 32 participants | 40 participants | 72 participants |
| Region of Enrollment United States | 63 participants | 66 participants | 129 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 63 | 49 / 66 |
| serious Total, serious adverse events | 1 / 63 | 3 / 66 |
Outcome results
Primary
4-week Continuous Abstinence From Smoking
This measure indicates the proportion of participants who did or did not smoke any cigarettes during the final 4 weeks of treatment, which represented weeks 8-12 of study participation.
Time frame: Weeks 8-12 of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topiramate | 4-week Continuous Abstinence From Smoking | 7.9 percentage of participants abstinent |
| Placebo | 4-week Continuous Abstinence From Smoking | 10.6 percentage of participants abstinent |
Secondary
Percent Relapsing to Any Drinking or Illicit Drug Use
Alcohol or illicit drug use during treatment or follow up.
Time frame: 12-week treatment phase, 36-week combined treatment and follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topiramate | Percent Relapsing to Any Drinking or Illicit Drug Use | 31.8 percentage of participants |
| Placebo | Percent Relapsing to Any Drinking or Illicit Drug Use | 27.3 percentage of participants |
p-value: 0.5195% CI: [0.4, 6.5]Regression, Logistic
p-value: 0.4595% CI: [0.66, 2.55]Regression, Cox