Innovative Approaches for Cocaine Pharmacotherapy

描述（由申请人提供）：概述MDU：药物治疗的创新方法 这是NIDA资助的P50研究中心的竞争性更新，该中心是NIDA的药物开发单位（MDU）之一。我们的MDU补充了宾夕法尼亚大学的长期研究计划，以开发有效的药物成瘾治疗方法。我们的MDU在宾夕法尼亚州/弗吉尼亚州成瘾研究中心（CSA）的保护伞内的整合使我们能够进行大量的专业研究（例如，专注于可卡因成瘾;药物治疗），独立于其他资助的计划，更普遍地集中在阿片类药物和其他类型的成瘾，或非药物研究计划。然而，MDU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。我们MDU的主题是测试用于管理“难以治疗”可卡因/酒精依赖患者的创新药物组合。以前我们的P50主要集中在几种类型的严重可卡因依赖，但患者的组合依赖已成为最常见的。这一群体对现有治疗的反应很差，过去很少受到研究的关注。 MDU CORE协调各组成部分，开展积极的试点计划，为希望专注于可卡因研究的年轻职业研究人员提供指导结构，并优先获得重要的现场资源：1）一般临床研究中心（GCRC）-进行安全性试验的住院设施; 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。试点项目是任何中心的关键部分，将强调使用动物模型和脑成像来测试未来临床试验候选药物的新药发现。本应用程序中的建议组件反映了开发原型，其中包含对未来5年内要完成的特定项目的描述。基本上，项目的安排是为了允许在人类受试者（正常对照和患者）中系统地研究新药的安全性和有效性。组分1在随机、安慰剂对照试验中评价了一种有前途的新型化合物托吡酯。组件2描述了一系列安全性/耐受性监测研究，这些研究在大型临床试验中联合用药之前是必要的。第三部分实施了一项大型对照试验，以评估可卡因-酒精依赖患者联合用药的疗效。组件4描述了一个模型，该模型识别药物反应的潜在个体遗传预测因素。

DESCRIPTION (provided by applicant): OVERVIEW MDU: Innovative Approaches for Cocaine Pharmacotherapy This is a competitive renewal of a NIDA-funded P50 Research Center that serves as one of NIDA's Medication Development Units (MDU). Our MDU complements Penn's longstanding research program to develop effective treatments for drug addiction. The integration of our MDU within the umbrella of the Penn/VA Center for the Studies of Addiction (CSA) allows us to conduct a substantial amount of specialty research (e.g., focused on cocaine addiction; pharmacotherapy treatments), independent of other funded programs that are more generally focused on opiates and other types of addiction, or, on non-medication research programs. Yet, the MDU benefits greatly from Center integration because it permits access to infrastructure resources not provided by this P50 Center. The theme of our MDU is testing innovative medication combinations for managing "hard-to-treat" cocaine/alcohol dependent patients. Previously our P50 focused primarily on several types of severe cocaine dependence, but patients with the combined dependence have become most common. This group responds poorly to existing treatments and has received little research attention in the past. The MDU CORE coordinates the components, conducts an active pilot program, provides a structure for mentoring young, career investigators who want to specialize in cocaine research, and has priority access to important on-site resources: 1) General Clinical Research Center (GCRC) - an inpatient facility for conducting safety trials; 2) Center bio-statistician; 3) web-based Data Management Unit, and 4) a specialty drug screen lab. The pilot program, a critical part of any center, will emphasize novel medication discovery using animal models and brain imaging to test medications that are candidates for future clinical trials. The proposed components in this application reflect developing prototypes, which contain descriptions of specific projects to be done over the next 5 years. Basically, projects are arranged to allow for novel medications to be systematically studied in human subjects (normal controls and patients} from safety through efficacy. Component 1 evaluates a promising novel compound, topirimate, in a randomized, placebo-controlled trial. Component 2 describes a series of safety/tolerability monitoring studies that are necessary prior to combining medications in a large clinical trial. Component 3 operationalizes a large controlled trial to evaluate the efficacy of combination medications in cocaine-alcohol dependent patients. Component 4 describes a model that identifies potential individual genetic predictors to medication response.