Multi-Site Controlled Trial of Cocaine Vaccine (6 of 6) Columbia University Site

可卡因疫苗多中心对照试验（6 / 6）哥伦比亚大学网站

• 批准号: 7514741
• 负责人: Frances Rudnick Levin
• 金额: $ 36.32万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7514741
• 关键词: AIDS pharmacotherapy; Abstinence; Acquired Immunodeficiency Syndrome; Acute; Address; Administrative Coordination; Adverse effects; All Sites; Antibodies; Antibody Formation; Antigen-Antibody Complex; Attenuated; Authorship; Back; Binding; Biological Assay; Blood - brain barrier anatomy; Blood Circulation; Brain; Censuses; Cholera Toxin Protomer B; Clinical Trials; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive Therapy; Communication; Complement; Connecticut; Coupled; Daily; Data; Data Analyses; Dose; Dropout; Drug Addiction; Drug abuse; Drug usage; Educational process of instructing; Electronic Mail; Electronics; Evaluation; Human; Illicit Drugs; Immunology; Industry; Injection of therapeutic agent; Joints; Laboratories; Lead; Letters; Manuals; Manufacturer Name; Measures; Medical; Medicine; Mental Depression; Methamphetamine; Monitor; Morbidity - disease rate; National Institute of Drug Abuse; New York; Nucleus Accumbens; Numbers; Outcome; Outpatients; Paper; Patient Self-Report; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacists; Pharmacologic Substance; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Population; Procedures; Process; Public Health; Publications; Qualifying; Randomized; Randomized Clinical Trials; Range; Rate; Recombinants; Recruitment Activity; Relapse; Reporting; Research; Research Personnel; Risk; Route; Safety; Sample Size; Sampling; Schedule; Site; Smoke; Smoking; Statistical Data Interpretation; Structure; Study Section; Telephone; Testing; Therapeutic; Time; TimeLine; Toxicology; Training; Treatment Protocols; United States Food and Drug Administration; Universities; Update; Urine; Vaccination; Vaccines; Variant; Week; Work; Writing; addiction; base; benzoylecgonine; college; contingency management; coping; cost; craving; data management; day; design; experience; follow-up; immunogenicity; innovation; intravenous administration; mortality; novel vaccines; placebo controlled study; prevent; programs; randomized placebo controlled trial; rapid technique; response; size; skills; symposium; vaccine effectiveness; vaccine efficacy

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: 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.

描述（由申请人提供）：这项为期 16 周、六中心、安慰剂对照的随机临床试验 (PC-RCT) 在 300 名可卡因依赖患者中进行，旨在测试新开发的可卡因活性疫苗 (TA-CD) 的功效）。所有六个中心在使用可卡因药物疗法进行 PC-RCT 方面都拥有丰富的 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）与安慰剂相比，在增加可卡因依赖患者各治疗组的戒除可卡因天数方面的功效。本研究的次要目标是：评估五次注射 TA-CD 的安全性和耐受性，评估 TA-CD 的免疫原性，研究可卡因使用水平的变化、可卡因的渴望或主观影响与抗体水平之间的相关性，最后，检查治疗反应的预测因素。之前对 TA-CD 疫苗的研究表明，两种剂量（100 和 400 ug）以及 12 周内注射 5 次的方案在临床上都是安全的，并且会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，并且总体可卡因使用量显着减少。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 水平与可卡因使用量的大幅减少相关）。之前的 PC-RCT 提供了效应量数据，用于计算 300 个样本量，潜在的脱落率高达 30%。为了提高这项为期 16 周的研究的保留率，我们将使用应急管理 (CM)，在一项试点研究中，该管理为为期 16 周的研究提供了超过 80% 的出色保留率。为了在三年内完成这项研究并合理地增加和保留这一困难人群，需要六个地点的参与。这六个非常合格的研究小组拥有可比较和互补的技能，可以研究通过疫苗接种提供医疗治疗的创新方法。这六个站点是： 贝勒医学院 (BCM)（牵头）；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；和哥伦比亚大学。所有这些合作者都与制药商 Celtic 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：可卡因依赖仍然是一个重大的公共卫生问题，导致大量发病率，有时甚至导致死亡率。迄今为止，还没有批准的可卡因依赖药物治疗方法。可卡因疫苗将在这项多地点合作治疗研究中进行测试，可能为这一持续存在的公共卫生问题提供创新且有效的治疗方法。