University of Texas Specialized Program in Acute Stroke

德克萨斯大学急性中风专业项目

• 批准号: 7633470
• 负责人: JAMES C GROTTA
• 金额: $ 160.49万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7633470
• 关键词: University; Texas; Specialized; Program; Acute

DESCRIPTION (provided by applicant): In this SPOTRIAS application, we propose 3 new studies, one of which (project #1) is a collaborative multicenter phase 2 trial across several SPOTRIAS centers, one entirely new project (project # 2), and one (project #3) which is the next phase of a project started during the first 5 years of our SPOTRIAS program. All three of these projects are translational in the true sense of the word. Project 1 is a trial of a combination of neuroprotective treatments (caffeinol and hypothermia), one of which (caffeinol) was discovered in our lab and has undergone extensive preclinical testing in our animal stroke models. The combination was also first tested in our lab. The phase 1 and early phase 2 evaluations of these treatments were part of the first SPOTRIAS from UT and UC San Diego, and showed feasibility and safety. In the spirit of translation, the study that we jointly propose in Project 1 is designed to replicate as much as possible the laboratory experiments which demonstrated the most robust benefit of this combination. The purpose of this study is to do a factorial design phase 2 study of both treatments alone and in combination compared with standard treatment in order to determine as quickly as possible which treatment arms should move forward to a phase 3 study. Project 2 is a study of a PPARgamma agonist in patients with ICH. Our lab was the first to demonstrate changes in PPARgamma expression in an animal model of ICH, and the PI of Project 2 was part of the lab team that first discovered that PPAR gamma agonists promoted the phagocytosis of the red blood cells comprising the hematoma. Project 2 is a direct clinical translation of that work. Finally, project 3 carries on our previous work with ultrasound enhanced clot lysis. The safety and benefit of ultrasound has been tested in our animal stroke models and in other labs, and then in a phase 2 study as part of our previous SPOTRIAS. In an effort to make this treatment more widely applicable, we have developed a hands-free ultrasound unit that we first tested in animals as part of a supplementary award to our first SPOTRIAS, and now propose to test for the first time in humans. We also propose 3 Cores (Clinical, Data, and Tissue) to support these translational studies, and a Career Development Program to train new investigators to carry out future translational studies. All of these projects and Cores were approved by the previous review of our grant, but there were concerns about the Data Core and Project #1 that we have thoroughly addressed in this re-submission.

描述（由申请人提供）：在此 SPOTRIAS 申请中，我们提出了 3 项新研究，其中一项（项目 #1）是跨多个 SPOTRIAS 中心的协作多中心 2 期试验，一项全新项目（项目 #2）和一项（项目 #3）这是我们 SPOTRIAS 计划前 5 年启动的项目的下一阶段。所有这三个项目都是真正意义上的转化。项目 1 是神经保护治疗（咖啡因和低温）组合的试验，其中一种（咖啡因）是在我们的实验室中发现的，并在我们的动物中风模型中进行了广泛的临床前测试。该组合也首先在我们的实验室进行了测试。这些治疗的 1 期和早期 2 期评估是 UT 和 UC San Diego 的第一个 SPOTRIAS 的一部分，并显示了可行性和安全性。本着翻译的精神，我们在项目 1 中共同提出的研究旨在尽可能多地复制实验室实验，这些实验证明了这种组合的最强大的好处。本研究的目的是对两种治疗单独和联合治疗与标准治疗进行比较进行析因设计 2 期研究，以便尽快确定哪些治疗组应进入 3 期研究。项目 2 是一项 PPARgamma 激动剂治疗 ICH 患者的研究。我们的实验室是第一个在ICH动物模型中证明PPARγ表达变化的实验室，项目2的PI是第一个发现PPARγ激动剂促进构成血肿的红细胞吞噬作用的实验室团队的成员。 项目 2 是该工作的直接临床转化。最后，项目 3 继续我们之前的超声增强凝块溶解工作。超声波的安全性和益处已在我们的动物中风模型和其他实验室中进行了测试，然后在作为我们之前 SPOTRIAS 一部分的第二阶段研究中进行了测试。为了使这种治疗方法得到更广泛的应用，我们开发了一种免提超声波装置，作为我们第一个 SPOTRIAS 补充奖励的一部分，我们首先在动物身上进行了测试，现在提议首次在人类身上进行测试。我们还提出了 3 个核心（临床、数据和组织）来支持这些转化研究，并提出了职业发展计划来培训新研究人员开展未来的转化研究。所有这些项目和核心都得到了我们之前拨款审查的批准，但也存在一些担忧 关于我们在这次重新提交中彻底解决的数据核心和项目#1。