Multisite Controlled Trial of Cocaine Vaccine (1of 6) Lead Site/ Houston Treatmen

描述（由申请人提供）：这项在300名可卡因依赖患者中进行的为期16周，6个地点，安慰剂对照的随机临床试验（PC-RCT）旨在测试新开发的抗可卡因活疫苗（TA-CD）的有效性。所有6个站点在使用可卡因药物治疗进行PC-RCT方面都具有丰富的NIDA经验。本研究的主要目的是评估两种不同剂量的TA-CD（100或400 ug）与安慰剂的疗效，以增加治疗组中可卡因依赖患者的无可卡因天数。本研究的次要目的是：评估五种注射TA-CD的安全性和耐受性，评估TA-CD的免疫原性，调查可卡因使用水平、渴望或可卡因主观效应与抗体水平的变化之间的相关性，最后，检查治疗反应的预测因子。以前对TA-CD疫苗的研究表明，两种剂量（100和400微克）和12周内5次注射的方案在临床上是安全的，并能产生大量的抗可卡因抗体。在之前的PC-RCT中，具有这些抗可卡因抗体（AB）的可卡因滥用者大大减少了吸食可卡因，并显着减少了总体可卡因使用量。该研究还表明，AB水平的预期变化是治疗反应的决定因素（例如，较高的AB水平与可卡因使用的较大减少有关）。之前的PC-RCT提供的效应量数据用于计算300的样本量，其中潜在的退出率高达30%。为了在这个为期16周的研究中提高保留率，我们将使用应急管理（CM），在一个试点研究中，它在16周的研究中提供了超过80%的出色保留率。为了在3年内完成这项研究，并对这些困难人群进行合理的累积和保留，需要六个站点的参与。这六个非常合格的研究小组具有可比性和互补性的技能，可以研究通过疫苗接种提供医疗治疗的创新方法。六个地点是：贝勒医学院（BCM），（领先）；辛辛那提大学；约翰霍普金斯大学；宾夕法尼亚大学；纽约大学；哥伦比亚大学。所有这些合作者都在与制药商凯尔特和NIDA合作，帮助进行定量尿液毒理学的数据管理和实验室处理。公共卫生相关性：需要新的方法来帮助治疗可卡因成瘾者，以成功地防止戒断后再次吸毒。刺激对可卡因产生强烈抗体反应的疫苗将有助于这些人，因为它可以阻止那些已经戒断的人在再次接触可卡因后产生的对毒品的渴望。这项研究将确定制造和有效使用这种疫苗的方法，以刺激高抗体水平，这将有最大的成功机会。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: New approaches are needed to help treat those addicted to cocaine to successfully keep from relapsing to drug abuse after withdrawal. Vaccines that stimulate strong antibody responses against cocaine will help such individuals by blocking the drug craving that occurs after re-exposure to cocaine in someone who has been abstinent. This research will define ways to make and effectively use such vaccines to stimulate high antibody levels that will have the best chance of success.