Multisite Controlled Trial of Cocaine Vaccine (4 of 6) Philadelphia Treatment Sit

可卡因疫苗多中心对照试验（第 4 次，共 6 次）费城治疗中心

• 批准号: 8277544
• 负责人: KYLE Matthew KAMPMAN
• 金额: $ 8.3万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8277544
• 关键词: AIDS pharmacotherapy; Abstinence; Acquired Immunodeficiency Syndrome; Acute; Address; Administrative Coordination; Adverse effects; 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; Cognitive Therapy; Communication; Complement; Connecticut; Coupled; Data; Data Analyses; Dose; Dropout; Drug Addiction; Drug abuse; Drug usage; Educational process of instructing; Electronic Mail; Evaluation; Health; Human; Illicit Drugs; Immunology; Individual; Industry; Injection of therapeutic agent; Joints; Laboratories; Lead; Letters; Manuals; Manufacturer Name; Measures; Medical; Medicine; Mental Depression; Methamphetamine; Monitor; National Institute of Drug Abuse; New York; Nucleus Accumbens; Outcome; Outpatients; Paper; Patient Self-Report; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacists; Pharmacologic Substance; Pharmacotherapy; Philadelphia; Pilot Projects; Placebo Control; Placebos; Population; Procedures; Process; Publications; Qualifying; Randomized; Randomized Clinical Trials; Recombinants; Recruitment Activity; Regimen; 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; Universities; Update; Urine; Vaccination; Vaccines; Variant; Withdrawal; Work; Writing; addiction; base; benzoylecgonine; cocaine exposure; cocaine use; college; contingency management; control trial; coping; cost; craving; data management; design; drug craving; efficacy testing; electronic data; experience; follow-up; immunogenicity; innovation; intravenous administration; meetings; multi-site trial; novel strategies; novel vaccines; placebo controlled study; prevent; primary outcome; programs; randomized placebo controlled trial; rapid technique; response; skills; success; symposium; treatment response; 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 5g) 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.

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、随机化临床试验（PC-RCT）旨在测试新开发的可卡因活性疫苗（TA-CD）的有效性。所有六个研究中心在进行可卡因药物治疗的PC-RCT方面都有大量的NIDA经验。本研究的主要目的是评价两种不同剂量的TA-CD（100或400 5g）与安慰剂相比在增加可卡因依赖患者治疗组间无可卡因天数方面的疗效。本研究的次要目的是：评价5次TA-CD注射的安全性和耐受性，评价TA-CD的免疫原性，研究可卡因使用水平、渴望或可卡因主观效应与抗体水平变化之间的任何相关性，最后检查治疗反应的预测因素。先前关于TA-CD疫苗的研究表明，两种剂量（100和400 μ g）和12周内注射5次的方案在临床上是安全的，并产生大量的抗可卡因抗体。在先前的PC-RCT期间，具有这些抗可卡因抗体（AB）的可卡因滥用者大大减少了他们吸食的可卡因，并且总体可卡因使用量显著减少。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水平与可卡因使用的较大减少相关）。先前的PC-RCT提供了用于计算样本量300的效应量数据，潜在脱落率高达30%。为了提高保留在这个为期16周的研究，我们将使用应急管理（CM），这在一个试点研究提供了超过80%的16周的研究优秀的保留。为了在3年内完成本研究并合理增加和保留这一困难人群，需要6家研究中心参与。这六个非常合格的研究小组具有可比和互补的技能，可以研究通过疫苗接种提供医学治疗的创新方法。这六个地点是：贝勒医学院（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凯尔特人和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复发滥用药物。刺激针对可卡因的强烈抗体反应的疫苗将通过阻断已经戒断的人在重新接触可卡因后发生的药物渴望来帮助这些人。这项研究将确定制造和有效使用此类疫苗的方法，以刺激高抗体水平，从而获得最佳成功机会。