Innovative Approaches for Cocaine Pharmacotherapy

描述(由申请人提供)：MDU概述：可卡因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开发有效治疗药物成瘾的长期研究计划。将我们的MDU整合到宾夕法尼亚大学/退伍军人管理局成瘾研究中心(CSA)的保护伞内，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)，独立于其他资助的项目，这些项目更一般地专注于阿片类药物和其他类型的成瘾，或非药物研究项目。然而，MDU从Center集成中获益良多，因为它允许访问此P50 Center未提供的基础设施资源。我们MDU的主题是测试创新的药物组合，以管理“难以治疗”的可卡因/酒精依赖患者。以前我们的P50主要集中在几种类型的严重可卡因依赖上，但合并依赖的患者已经变得最常见。这一群体对现有的治疗方法反应很差，过去很少受到研究关注。 MDU核心协调各组成部分，实施积极的试点计划，为希望专门从事可卡因研究的年轻职业调查人员提供指导结构，并优先获得重要的现场资源：1)综合临床研究中心(GCRC)-进行安全试验的住院设施；2)中心生物统计师；3)基于网络的数据管理单位，以及4)特殊药物筛选实验室。试点计划是任何中心的关键部分，将强调使用动物模型和大脑成像来测试未来临床试验候选药物的新药发现。本申请中建议的组件反映了正在开发的原型，其中包含对未来5年将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(正常对照组和患者)中系统地研究从安全性到有效性的新型药物。成分1在一项随机的安慰剂对照试验中评估了一种有前景的新化合物托吡酯。第二部分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。第三部分开展了一项大型对照试验，以评估联合用药对可卡因-酒精依赖患者的疗效。组成部分4描述了一个模型，该模型确定了潜在的个体对药物反应的遗传预测因素。

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.