Alcoholism, Cocaine Dependence
Conditions
Keywords
Topiramate, alcoholism, cocaine dependence
Brief summary
The primary purpose of this study is to test the effectiveness of topiramate for the treatment of combined alcohol and cocaine dependence. Topiramate is approved for the treatment of seizures. It has not been proven to be effective for the treatment of alcohol or cocaine dependence.
Detailed description
The purpose of this study is to evaluate the efficacy of 300 mg/day of topiramate for the treatment of 200 treatment-seeking alcohol dependent outpatients with comorbid cocaine dependence in a double-blind, placebo-controlled 14-week trial, with a 6-month follow-up (3 months after completing medications).
Interventions
DRUGTopiramate
300mg/day for 13 weeks
DRUGplacebo
placebo pills
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Kyle Kampman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and females, 18 years or older. * Meets DSM(Diagnostic and Statistical Manual)-IV criteria for current diagnoses of cocaine and alcohol dependence, determined by the SCID (Structured Clinical Interview for the DSM)-IV. * In the past 30 days, used no less than $200-worth of cocaine and meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell and Sobell, 1995) a. drank within 30 days of intake day, b. reports a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting intake (i.e., a minimum of 40% days drinking), and c. has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period. * Two consecutive days of abstinence from cocaine and alcohol, determined by self-reports and confirmed by negative urine toxicology screens, a negative breathalyzer tests, and collateral report, a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan et al., 1989) score below eight,. Subjects will be encouraged to achieve 3 consecutive days of abstinence, however, subjects who have achieved 2 consecutive days of abstinence will be included with the approval of the principal investigator. We anticipate that these subjects will comprise less than 5% of total enrolled subjects. Subjects will be given 2 additional weeks beyond the screening week to attain the appropriate period of cocaine and alcohol abstinence prior to randomization. * Lives a commutable distance from the Treatment Research Center (TRC) and agrees to attend all research visits including follow-up visits. * Speaks, understands, and prints in English.
Exclusion criteria
* Abstinent from cocaine or alcohol for 30 consecutive days prior to signing consent form. * Meets DSM-IV criteria for dependence on any substance other than cocaine and alcohol (except nicotine and cannabis), determined by the SCID. * Needs treatment with any psychoactive medications including any anti-seizure medications (with the exception of Benadryl used sparingly, if necessary, for sleep). * Current use of phenytoin or any drug of similar class. * Meets DSM-IV criteria for schizophrenia or any psychotic disorder, or organic mental disorder. Subject meets current DSM-IV diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation. * Has evidence of a history of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease. * Severe physical or medical illnesses such as AIDS, active hepatitis, significant hepatocellular injury as evidenced by elevated bilirubin levels (\>1.3), or elevated levels (over 3.5x normal) of aspartate aminotransferase (AST), and serum glutamic-pyruvic transaminase (SGPT) after the required 3 days of abstinence, or severe renal disease, severe respiratory diseases or severe diarrhea with resulting metabolic acidosis, serum bicarbonate (\< 20 milliequivalent (mEq)/L) * History of epilepsy or seizure disorder. * Use of an investigational medication in the 30 days prior to randomization. * History of nephrolithiasis (kidney stones). * History of hypersensitivity to topiramate. * Is female and tests positive on a pregnancy test, is contemplating pregnancy in the next 6 months, is nursing, or is not using an effective contraceptive method (if relevant). Acceptable methods of contraception include barrier methods (diaphragm or condom with spermicide, intrauterine progesterone contraceptive system, levonorgestrel implant, and medroxyprogesterone acetate contraceptive injection). * Current use of a carbonic anhydrase inhibitor. * A history of glaucoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants Abstinent From Cocaine During Last 3 Weeks of 13 Week Trial | Last 3 weeks of 13 week trial | Samples were analyzed for benzoylecgonine by fluorescent polarization assay. Samples containing equal to or greater than 300 ng/ml of benzoylecgonine were considered to be positive for cocaine. |
| Number of Heavy Drinking Days | 13 weeks | Heavy drinking days, defined as more than 4 standard drinks for men and 3 standard drinks for women |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cocaine Withdrawal Symptoms Measured by Cocaine Selective Severity Assessment. | 13 weeks | Total cssa score at the end of the medication phase of the trial. The CSSA is a measure of cocaine withdrawal severity. The minimum score is 0 the maximum score is 119. Higher score means more severe cocaine withdrawal symptoms |
| The Penn Alcohol Craving Scale | 13 weeks | This Scale measures alcohol craving. The maximum score is 30, the minimum score is 0. Higher scores are indicative of more severe alcohol craving. |
Countries
United States
Participant flow
Recruitment details
Recruitment for this study began on 11/1/2004 and ended five years later in November 2009. Participants were treatment-seeking cocaine and alcohol users recruited at the UPenn Treatment Research Center.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 topiramate
Topiramate : 300mg/day for 13 weeks | 83 |
| Group 2 placebo : placebo pills | 87 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Drowsy | 1 | 0 |
| Overall Study | Incarcerated | 3 | 2 |
| Overall Study | Lost to Follow-up | 20 | 31 |
| Overall Study | Withdrawal by Subject | 5 | 8 |
Baseline characteristics
| Characteristic | Group 2 | Group 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 87 Participants | 83 Participants | 170 Participants |
| Age, Continuous | 43 years STANDARD_DEVIATION 8 | 45 years STANDARD_DEVIATION 7 | 44 years STANDARD_DEVIATION 7 |
| Region of Enrollment United States | 87 participants | 83 participants | 170 participants |
| Sex: Female, Male Female | 18 Participants | 18 Participants | 36 Participants |
| Sex: Female, Male Male | 69 Participants | 65 Participants | 134 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 83 | 0 / 87 |
| other Total, other adverse events | 46 / 83 | 24 / 87 |
| serious Total, serious adverse events | 0 / 83 | 0 / 87 |
Outcome results
Primary
Number of Heavy Drinking Days
Heavy drinking days, defined as more than 4 standard drinks for men and 3 standard drinks for women
Time frame: 13 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topirmate | Number of Heavy Drinking Days | 5.21 number of heavy drinking days | Standard Error 0.58 |
| Placebo | Number of Heavy Drinking Days | 6.10 number of heavy drinking days | Standard Error 0.61 |
p-value: 0.45Generalized Estimating Equations
Primary
Percent of Participants Abstinent From Cocaine During Last 3 Weeks of 13 Week Trial
Samples were analyzed for benzoylecgonine by fluorescent polarization assay. Samples containing equal to or greater than 300 ng/ml of benzoylecgonine were considered to be positive for cocaine.
Time frame: Last 3 weeks of 13 week trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topirmate | Percent of Participants Abstinent From Cocaine During Last 3 Weeks of 13 Week Trial | 17 Percent of participants |
| Placebo | Percent of Participants Abstinent From Cocaine During Last 3 Weeks of 13 Week Trial | 6 Percent of participants |
p-value: 0.01Chi-squared
Secondary
Cocaine Withdrawal Symptoms Measured by Cocaine Selective Severity Assessment.
Total cssa score at the end of the medication phase of the trial. The CSSA is a measure of cocaine withdrawal severity. The minimum score is 0 the maximum score is 119. Higher score means more severe cocaine withdrawal symptoms
Time frame: 13 weeks
Population: Subjects present during the last week of the trial
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topirmate | Cocaine Withdrawal Symptoms Measured by Cocaine Selective Severity Assessment. | 9.9 score on a scale | Standard Deviation 9.5 |
| Placebo | Cocaine Withdrawal Symptoms Measured by Cocaine Selective Severity Assessment. | 8.4 score on a scale | Standard Deviation 8.8 |
p-value: 0.495% CI: [-2.1, 5.2]t-test, 2 sided
Secondary
The Penn Alcohol Craving Scale
This Scale measures alcohol craving. The maximum score is 30, the minimum score is 0. Higher scores are indicative of more severe alcohol craving.
Time frame: 13 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topirmate | The Penn Alcohol Craving Scale | 7.90 score on a scale | Standard Deviation 6.86 |
| Placebo | The Penn Alcohol Craving Scale | 9.29 score on a scale | Standard Deviation 6.48 |