Alcoholism, Cocaine Dependence
Conditions
Brief summary
The purpose of this study is to evaluate the effectiveness of vigabatrin at reducing drug and alcohol use in individuals addicted to cocaine and alcohol. Vigabatrin 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 hypotheses in the proposed study will be tested with a 2-group design to assess the efficacy of vigabatrin compared to placebo. We will follow NIAAA's COMBINE Medical Management (MM) manual in weekly dispensing medications, safety checks and medication adherence. The psychosocial treatment will be Cognitive Behavioral Coping Skills Therapy (CBT). Subjects will be 60 men and women with current DSM-IV diagnoses of both cocaine and alcohol dependence who will be randomized to vigabatrin or placebo (30 subjects per group). All subjects will receive weekly sessions of CBT. The study length for each subject is comprised of a1-3 weeks of screening and baseline evaluations, an 8-week double-blind, placebo-controlled trial with CBT (medication phase), and one follow-up visit 12 weeks after starting study medication. Study medication will be initiated in Week 2. The research physician will explain the dosing regimen and subjects will be randomly assigned to receive either vigabatrin or identical placebo tablets. Subjects will receive 1 gram of vigabatrin or identical placebo tablets on medication days 1-3 then 1.5 grams or identical placebo tablets on days 4-7. The dose ids increased to 2 grams in week 2, 3 grams in weeks 4-7 and then reduced to 2 grams days 50-53, and to 1 gram on days 54-56
Interventions
DRUGVigabatrin
Vigabatrin escalated to 3 grams daily for 8 weeks
DRUGPlacebo
Placebo pills
Sponsors
National Institute on Drug Abuse (NIDA)
University of Pennsylvania
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
1. Male and females, 18 years of age or older. 2. Meets DSM-IV criteria for current diagnoses of cocaine and alcohol dependence, determined by the SCID-IV. 3. Used cocaine in the past 30 days and used no less than $200 of cocaine in a consecutive 30 day period over the 90 day period prior to intake. Meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell 1995) a drank within 30 days of intake day, b. reports a minimum of 48 standard alcoholic (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 greater than 4 drinks per day in males and greater than 3 drinks per day in females) in this same pre-treatment period. 4. Three consecutive days of abstinence from alcohol directly prior to the day of randomization, determined by self-reports and confirmed by negative breathalyzer tests, and a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan and Sellers 1989) score below eight. Subjects will be given 2 additional weeks beyond the screening week to attain the appropriate period of alcohol abstinence prior to randomization. 5. Have a verifiable address of principal residence, lives a commutable distance from the TRC and agrees to attend all research visits including follow-up visits. 6. Speaks, understands, and prints in English 7. Ability to give informed consent
Exclusion criteria
1. 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 diphenhydramine used sparingly, if necessary, for sleep). 2. Meets current or lifetime 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 as determined by the principal investigator. 3. Has evidence of a history of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease. 4. Severe physical or medical illnesses such as AIDS, active hepatitis, significant hepatocellular injury as evidenced by elevated total bilirubin levels (\>1.3 mg/dl), or elevated levels (over 4.5x normal) of aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT). Patients with Gilberts Syndrome will not be excluded. 5. Use of an investigational medication in the 30 days prior to randomization. 6. History of prior treatment with vigabatrin 7. History of prior treatment with drugs with known retinotoxicity 8. History of visual field defects or predisposing factors, including glaucoma, severe myopia, retinal disorders, cataracts, diabetes, or uncontrolled hypertension. 9. 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, female condom), intrauterine progesterone contraceptive system, levonorgrestrel implant, and medroxyprogesterone acetate contraceptive injection, copper IUD, vaginal contraceptive film, cervical cap, contraceptive foam, hormonal vaginal contraceptive ring (NuvaRing®) or oral contraceptives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Reduction in Cocaine Use | last 3 weeks of the trial | The primary outcome measure for reduction in cocaine use will be the number of benzoylecgonine (BE) negative urine samples. The main outcome is the number of participants in each group who reported all BE negative urine samples in the last three weeks of the trial. |
| Proportion of Heavy Drinking Days | 8 weeks | The primary outcome measure for reduction in alcohol use will be recorded using the Timeline Followback method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measures of Cocaine Craving | 8 weeks | Measures of cocaine craving at the end of the trial will be measured using the Brief Substance Craving Ccale. Craving intensity + Craving frequency + Craving Duration each measured on a 4 point scale. Sum of the three scales was overall craving composite. Higher numbers meaning greater craving. Maximum score 12 minimum 0. |
| Disease Severity and Improvement | 8 weeks | Number of subjects in each group rated as improved or very much improved at the end of the trial |
| Cocaine Withdrawal Severity | 8 weeks | Measure of cocaine withdrawal severity will include Cocaine Selective Severity Assessment scores. Minimum score is 0 Maximum score is 119 Higher score is indicative of worse cocaine withdrawal symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vigabatrin Vigabatrin: Vigabatrin escalated to 3 grams daily for 8 weeks | 16 |
| Placebo Placebo: Placebo pills | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Placebo | Vigabatrin | 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 | 16 Participants | 16 Participants | 32 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 6.81 | 46 years STANDARD_DEVIATION 7.97 | 47 years STANDARD_DEVIATION 7.35 |
| Region of Enrollment United States | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 16 | 13 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Number of Participants With a Reduction in Cocaine Use
The primary outcome measure for reduction in cocaine use will be the number of benzoylecgonine (BE) negative urine samples. The main outcome is the number of participants in each group who reported all BE negative urine samples in the last three weeks of the trial.
Time frame: last 3 weeks of the trial
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vigabatrin | Number of Participants With a Reduction in Cocaine Use | 0 participants |
| Placebo | Number of Participants With a Reduction in Cocaine Use | 2 participants |
p-value: 0.14Chi-squared
Primary
Proportion of Heavy Drinking Days
The primary outcome measure for reduction in alcohol use will be recorded using the Timeline Followback method.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vigabatrin | Proportion of Heavy Drinking Days | .26 proportion of heavy drinking days | Standard Deviation 0.18 |
| Placebo | Proportion of Heavy Drinking Days | .20 proportion of heavy drinking days | Standard Deviation 0.25 |
Secondary
Cocaine Withdrawal Severity
Measure of cocaine withdrawal severity will include Cocaine Selective Severity Assessment scores. Minimum score is 0 Maximum score is 119 Higher score is indicative of worse cocaine withdrawal symptoms.
Time frame: 8 weeks
Population: subjects receiving vigabatrin or placebo who were available at the end of the trial to provide data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vigabatrin | Cocaine Withdrawal Severity | 8.0 score on a scale | Standard Deviation 8.1 |
| Placebo | Cocaine Withdrawal Severity | 6.5 score on a scale | Standard Deviation 6.8 |
p-value: 0.64t-test, 2 sided
Secondary
Disease Severity and Improvement
Number of subjects in each group rated as improved or very much improved at the end of the trial
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vigabatrin | Disease Severity and Improvement | 5 Participants |
| Placebo | Disease Severity and Improvement | 2 Participants |
p-value: 0.2Chi-squared
Secondary
Measures of Cocaine Craving
Measures of cocaine craving at the end of the trial will be measured using the Brief Substance Craving Ccale. Craving intensity + Craving frequency + Craving Duration each measured on a 4 point scale. Sum of the three scales was overall craving composite. Higher numbers meaning greater craving. Maximum score 12 minimum 0.
Time frame: 8 weeks
Population: subjects receiving vigabatrin or placebo who were available at the end of the trial to provide data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vigabatrin | Measures of Cocaine Craving | 1.44 score on a scale | Standard Deviation 2.3 |
| Placebo | Measures of Cocaine Craving | 0.38 score on a scale | Standard Deviation 1.1 |
p-value: 0.24t-test, 2 sided