This 20 week, placebo-controlled randomized clinical trial among 120 methadone maintained cocaine abusing patients is designed to test the efficacy of a newly developed active vaccine against cocaine (TA-CD) in conjunction with cognitive behavioral therapy (CBT). This vaccine generates antibodies that can retain cocaine in the bloodstream and allow naturally occurring cholinesterases to convert cocaine into inactive metabolites. Previous work by this investigator has shown a dose (100ug) and regimen (4 injections over 8 weeks) among cocaine abusers is clinically safe and produces substantial levels of anti-cocaine antibodies that persist for at least 3 months after final vaccination. TA-CD is however limited by two factors: 1) antibodies take 6-8 weeks following multiple inoculations to rise to effective levels, and 2) although it reportedly attenuates the subjective effects of cocaine, it can be over-ridden by increasing cocaine doses. To address these limitations, methadone maintenance will retain patients while the vaccine becomes effective, and the CBT will encourage abstinence. Because initial cocaine abstinence carries a good prognosis and we hypothesize that TA-CD's optimal efficacy will be to maintain this abstinence, we will stratify patients on their ability to attain a week of abstinence during an initial 2-week run-in period prior to randomization. Thus, during weeks 1-10 subjects will be maintained on methadone and learn the skills of CBT, at week 3 they will be randomized to vaccine or placebo and by week 10 complete the vaccine regimen of 4 injections over 8 weeks. Weeks 11-20 will provide clinical trial testing of the efficacy of TA-CD vs. placebo. Follow-ups at weeks 24, 28, & 32 will track any decline in antibody levels as well as cocaine use. To allow for analyses based on variation in antibody levels patients will be randomized in a 2 to 1 ratio of active to placebo (80 to 40 patients). Outcomes include treatment retention and 3 times per week urines for cocaine metabolites. Because the levels of antibody are expected to vary across individuals, antibody levels will be used as a covariate in analyses of outcome.
