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

可卡因疫苗多中心对照试验（6 中之一）牵头中心/Houston Treatmen

• 批准号: 7685479
• 负责人: THOMAS Richard KOSTEN
• 金额: $ 58.69万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 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/7685479
• 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; 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 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.

描述(申请人提供)：这项为期16周、6个地点的安慰剂随机临床试验(PC-RCT)在300名可卡因依赖患者中进行，旨在测试一种新开发的可卡因活性疫苗(TA-CD)的有效性。所有六个网站在进行可卡因药物疗法的PC-RCT方面都有丰富的NIDA经验。这项研究的主要目的是评估两种不同剂量的TA-CD(100或400微克)与安慰剂相比，在可卡因依赖患者的治疗组中增加无可卡因天数的有效性。这项研究的次要目标是：评估五种TA-CD注射的安全性和耐受性，评估TA-CD的免疫原性，调查可卡因使用水平、渴求或可卡因主观影响的变化与抗体水平之间的任何相关性，最后检查治疗反应的预测因素。先前对TA-CD疫苗的研究表明，两种剂量(100和400微克)以及在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。在之前的PC-RCT中，使用这些抗可卡因抗体(AB)的可卡因滥用者大幅减少了吸烟的可卡因，并显著减少了总体可卡因的使用。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，AB水平越高，可卡因使用的减少越大)。以前的PC-RCT提供了用于计算300个样本量的效应量数据，潜在的丢失率高达30%。为了在这项为期16周的研究中提高保留率，我们将使用应急管理(CM)，在一项试点研究中，它为16周的研究提供了超过80%的保留率。要在3年内完成这项研究，并对这一困难群体进行合理的积累和保留，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，可以研究通过接种疫苗提供药物治疗的创新方法。这六个网站是：贝勒医学院(BCM)，(LEAD)；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；以及哥伦比亚大学。所有这些合作者都在与制药制造商凯尔特人和NIDA合作，帮助进行数据管理和实验室处理，进行定量尿液毒理学研究。与公共卫生相关：需要新的方法来帮助治疗那些对可卡因上瘾的人，以成功地防止戒毒后再次吸毒。刺激针对可卡因的强烈抗体反应的疫苗将通过阻止戒毒者再次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这种疫苗的方法，以刺激最有可能成功的高抗体水平。