Innovative Approaches for Cocaine Pharmacotherapy

描述（由申请人提供）：这是一个由NIDA资助的P50中心，作为卓越的药物开发中心（MDCE）的竞争性更新。我们的MDCE补充了宾夕法尼亚大学的长期研究计划，以开发有效的成瘾治疗。我们的MDCE被整合在PennA/A成瘾研究中心的保护伞内，使我们能够专注于可卡因酒精依赖（CAD）的药物治疗。然而，MDCE从中心集成中受益匪浅，因为它允许访问P50中心不提供的基础设施资源。MDCE可优先访问重要资源：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）基于网络的数据管理单元;以及4）专业药物筛选实验室。我们的主题是测试用于管理“难以治疗”的CAD患者的创新药物组合。这一组对现有治疗反应差，并且是众所周知的治疗不依从性。我们的MDCE建议继续单独测试新药物，并重点关注尚未获得FDA批准的新药，以及改进的治疗依从性程序。CORE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，进行药物组合及其与可卡因和/或酒精相互作用的安全性研究，并为新的研究人员提供指导结构。神经核心试点计划强调多维神经成像-行为-遗传模型，该模型确定了对MDCE组件中研究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。项目的安排允许从安全性到有效性对新药进行研究，单独和组合，以便从现有的候选药物中为临床试验做出更明智的选择。第1部分建议在为期9周的安慰剂对照试验中评估有前途的新化合物。第二部分提出了人类实验室研究，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。通过从大量的候选药物开始，并按上述顺序进行测试，我们希望更快地确定有效的药物，以证明下一个发展水平：多中心试验。公共卫生相关性：可卡因和酒精依赖并存在这个国家仍然很常见，是一个有据可查的“难以治疗”的公共卫生问题。研究“错过”的机会，研究这个问题，由于解决组合依赖性研究设计的复杂性。这个P50中心的目标是弥合我们关于如何最好地治疗这一患者群体的知识差距。 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