Innovative Approaches for Cocaine Pharmacotherapy

描述（由申请人提供）：这是nida资助的P50中心的竞争性更新，该中心作为卓越药物开发中心（MDCE）。我们的MDCE补充了宾夕法尼亚大学长期以来开发有效成瘾治疗的研究项目。我们的MDCE整合在PennA/A成瘾研究中心的框架内，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P50中心没有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——用于人体实验室试验的住院/门诊设施；2)中心生物统计学家；3)网络数据管理单位；4)专业药物筛选实验室。我们的主题是测试创新的药物组合来管理“难以治疗”的CAD患者。这个群体对现有的治疗反应很差，并且是出了名的治疗不依从。我们的MDCE建议继续对新药物进行单独和联合测试，重点是尚未获得FDA批准的新药物，以及改进的治疗依从性程序。核心项目将协调和整合“神经”核心试点项目和三个组成部分。核心职能还包括确定候选药物，开展药物组合及其与可卡因和/或酒精相互作用的安全性研究，并为新的调查人员提供指导结构。Neuro Core试点项目强调了一个多维神经成像-行为-遗传模型，该模型确定了MDCE组件中要研究的药物反应的个体预测因子。组件反映了开发原型，其中包含对未来5年计划的项目的描述。项目安排允许从安全性到有效性，单个和组合研究新药物，以便从现有的候选药物组中做出更明智的临床试验选择。成分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。第二部分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，并为这些化合物提供更多的安全性数据。组件3将测试特定药物组合对CAD的疗效。通过从大量候选药物开始，并按照上述顺序进行测试，我们希望能够更快地确定有效的药物，从而证明下一阶段的开发是合理的：多位点试验。

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.