Innovative Approaches for Cocaine Pharmacotherapy

描述(由申请人提供)：这是NIDA资助的P50中心的竞争性续签，该中心作为卓越药物开发中心(MDCE)。我们的MDCE是对宾夕法尼亚大学开发有效成瘾治疗的长期研究计划的补充。我们的MDCE集成在Penna/A成瘾研究中心的保护伞下，使我们能够专注于可卡因酒精依赖(CAD)的药物治疗。然而，MDCE从中心集成中获益良多，因为它允许访问非P50中心提供的基础设施资源。MDCE优先获得重要资源：1)临床转化研究中心--人体实验室试验的住院/门诊设施；2)中心生物统计学家；3)基于网络的数据管理单位；以及4)特殊药物筛选实验室。我们的主题是测试创新的药物组合，以管理“难以治疗”的冠心病患者。这组人对现有的治疗反应很差，而且出了名的是治疗不依从性。我们的MDCE建议继续单独测试新药，并结合强调尚未获得FDA批准的新药，以及改进的治疗依从性程序。核心将协调和整合“神经”核心试点计划和三个组成部分。核心职能还确定候选药物，对药物组合及其与可卡因和/或酒精的相互作用进行安全性研究，并为新的调查人员提供指导结构。神经核心试验计划强调一个多维神经成像-行为-遗传模型，该模型确定MDCE组件中要研究的药物反应的个体预测因素。这些组成部分反映了正在开发的原型，其中包含对未来5年计划的项目的描述。项目的安排是为了能够从安全性和有效性方面研究新的药物，无论是单独的还是联合的，以便从现有的候选药物中进行更多知情的临床试验选择。组成部分1建议在为期9周的安慰剂对照试验中评估有前景的新化合物。组成部分2建议进行人体实验室研究，以评估这些化合物可能减少可卡因使用的机制，也为这些化合物提供更多的安全数据。组件3将测试特定药物组合对冠心病的疗效。通过从大量候选药物开始并按所述顺序进行测试，我们希望更快地确定有效的药物，以证明下一阶段的开发是合理的：多地点试验。与公共卫生相关：可卡因和酒精依赖并存的情况在这个国家仍然很常见，这是一个公共健康问题，有很好的记录表明这是一个“难以治疗”的问题。由于处理组合相关性研究设计的复杂性，研究“错失”了研究这个问题的机会。这个P50中心的目标是弥合我们在如何最好地治疗这一患者群体方面的知识差距。 中心特征

DESCRIPTION (provided by applicant): This is a competitive renewal of a NIDA-funded P50 Center that serves as a Medication Development Center of Excellence (MDCE). Our MDCE complements Penn's longstanding research program to develop effective addiction treatments. Our MDCE is integrated within the umbrella of the PennA/A Center for the Study of Addiction, allowing us to focus on pharmacotherapy for cocaine alcohol dependence (CAD). Yet, the MDCE benefits greatly from Center integration because it permits access to infrastructure resources not provided by a P50 Center. The MDCE has priority access to important resources: 1) Clinical Translational Research Center - an inpatient/outpatient facility for human laboratory trials; 2) Center bio-statistician; 3) web-based Data Management Unit; and, 4) a specialty drug screen laboratory. Our theme is testing innovative medication combinations for managing "hard-to-treat" CAD patients. This group responds poorly to existing treatments and is notoriously treatment nonadherent. Our MDCE proposes to continue testing new medications singly and in combination with an emphasis on novel medications not yet approved by the FDA, plus improved treatment adherence procedures. The CORE will coordinate and integrate a "Neuro" Core Pilot Program and three Components. Core functions also identify candidate medications, conduct safety studies of medication combinations and their interactions with cocaine and/or alcohol, and provide a mentoring structure for new investigators. The Neuro Core Pilot Program emphasizes a multidimensional neuroimaging-behavioral-genetic model that identifies individual predictors of response to the medications to be studied in MDCE Components. The Components reflect developing prototypes, which contain descriptions of projects planned over the next 5 years. Projects are arranged to allow for novel medications to be studied from safety through efficacy, singly and in combination, to make more informed selections for clinical trials from among the group of candidates now available. Component 1 proposes to evaluate promising novel compounds in 9-week placebo-controlled trials. Component 2 proposes human lab studies to evaluate the mechanisms by which those compounds may decrease cocaine use, also providing more safety data for these compounds. Component 3 will test the efficacy of specific medication combinations for CAD. By starting with a large number of candidate medications and sequentially testing as described, we hope to more rapidly identify effective medications that justify the next level of development: Multi-site trials. PUBLIC HEALTH RELEVANCE: Co-occurring cocaine and alcohol dependence continues to be common in this country, and represents a public health problem that is well documented as "hard to treat". Research has "missed" opportunities to study this problem due to the complexities of addressing combined dependencies study designs. The goal of this P50 Center is to bridge the gap in our knowledge about how best to treat this patient population. CENTER CHARACTERISTICS