This 16 week, six-site, placebo-controlled randomized, clinical trial (PC-RCT) among 300 cocaine dependent patients is designed to test the efficacy of a newly developed active vaccine against cocaine (TA-CD). All six sites have substantial NIDA experience in conducting PC-RCT with cocaine pharmacotherapies. The primary objective of this study is to evaluate the efficacy of two different doses of TA-CD (100 or 400 ug) versus placebo to increase the number of cocaine-free days across treatment groups in cocaine-dependent patients. Secondary objectives of this study are: to evaluate safety and tolerability of five injections of TA-CD, to evaluate immunogenicity of TA-CD, to investigate any correlation between change in levels of cocaine use, craving, or subjective effects of cocaine and antibody levels, and finally, to examine predictors of treatment response. Previous work with the TA-CD vaccine has shown both doses (100 and 400 ug) and a regimen of 5 injections over 12 weeks are clinically safe and produce substantial levels of anti-cocaine antibody. During a previous PC-RCT, cocaine abusers with these anti-cocaine antibodies (AB) substantially reduced their smoked cocaine and had a significant reduction in overall cocaine use. That study also showed an expected variation in AB levels was a determinant of therapeutic response (e.g. higher AB levels were associated with a greater reduction in cocaine use). That previous PC-RCT provided effect size data for calculating the sample size of 300 with a potential dropout of up to 30%. In order to enhance retention in this 16-week study, we will use contingency management (CM), which in a pilot study provided outstanding retention of over 80% for a 16-week study. To complete this study within a 3-year period and have reasonable accrual and retention of this difficult population requires participation of six sites. These six extremely well qualified research groups have comparable and complementary skills that can examine innovative ways to deliver a medical therapy through vaccination. The six sites are: Baylor College of Medicine (BCM), (lead); University of Cincinnati; Johns Hopkins University; University of Pennsylvania; New York University; and, Columbia University. All of these collaborators are working with the pharmaceutical manufacturer--Celtic, and NIDA to help with data management and laboratory processing for quantitative urine toxicology.
Cocaine dependence remains a significant public health problem that produces substantial morbidity and at times, mortality. To date, there is no approved pharmacologic treatment for cocaine dependence. The cocaine vaccine, which will be tested in this multi-site, collaborative treatment study, may provide an innovative and effective treatment for this persistent public health problem. ? ? ?