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: 8266888
• 负责人: Sean I Savitz
• 金额: $ 203.96万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8266888
• 关键词: Address; Agonist; Animal Model; Animals; Award; Clinical; Clinical Data; Coagulation Process; Cytolysis; Data; Erythrocytes; Evaluation; Future; Grant; Hand; Hematoma; Human; Laboratories; Modeling; PPAR gamma; Patients; Phagocytosis; Phase; Phase II Clinical Trials; Preclinical Testing; Research Personnel; Safety; Stroke; Testing; Texas; Time; Tissues; Training; Translations; Ultrasonography; Universities; Work; acute stroke; arm; career development; design; natural hypothermia; phase 2 study; phase 3 study; programs; research study; standard care; translational study

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.

在这个SPOTRIAS申请中，我们提出了3个新的研究，其中一个（项目#1）是跨几个SPOTRIAS中心的多中心合作二期试验，一个全新的项目（项目# 2），一个（项目#3）是我们SPOTRIAS计划前5年开始的项目的下一阶段。这三个项目都是真正意义上的翻译。项目1是神经保护治疗（咖啡因和低温）的组合试验，其中一种（咖啡因）是在我们的实验室发现的，并在我们的动物中风模型中进行了广泛的临床前测试。这种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2期早期评估是UT和UC圣地亚哥的第一个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。本研究的目的是进行一项因子设计的2期研究，将单独治疗和联合治疗与标准治疗进行比较，以便尽快确定哪些治疗组应该进入3期研究。项目2是对脑出血患者的PPARgamma激动剂的研究。我们的实验室是第一个在脑出血动物模型中证明PPAR γ表达变化的实验室，项目2的PI是第一个发现PPAR γ激动剂促进血肿红细胞吞噬的实验室团队的一部分。项目二是对这项工作的直接临床转化。最后，项目3继续我们先前的超声增强凝块溶解的工作。超声的安全性和益处已经在我们的动物中风模型和其他实验室进行了测试，然后在我们之前的SPOTRIAS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装置，我们首先在动物身上进行了测试，作为我们第一个SPOTRIAS的补充奖励的一部分，现在我们打算首次在人体上进行测试。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，以及一个职业发展计划来培训新的研究者进行未来的转化研究。所有这些项目和核心都通过了我们之前的拨款审查，但关于数据核心和项目#1的担忧，我们在这次重新提交中已经彻底解决了。

项目成果

Thrombus burden is associated with clinical outcome after intra-arterial therapy for acute ischemic stroke.

• DOI: 10.1161/strokeaha.108.521054
• 发表时间: 2008-12
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Barreto AD;Albright KC;Hallevi H;Grotta JC;Noser EA;Khaja AM;Shaltoni HM;Gonzales NR;Illoh K;Martin-Schild S;Campbell MS 3rd;Weir RU;Savitz SI
• 通讯作者: Savitz SI

Results of the ICTuS 2 Trial (Intravascular Cooling in the Treatment of Stroke 2).

• DOI: 10.1161/strokeaha.116.014200
• 发表时间: 2016-12
• 期刊: Stroke
• 影响因子: 8.3
• 作者: Lyden P;Hemmen T;Grotta J;Rapp K;Ernstrom K;Rzesiewicz T;Parker S;Concha M;Hussain S;Agarwal S;Meyer B;Jurf J;Altafullah I;Raman R;Collaborators
• 通讯作者: Collaborators

Intravenous rt-PA: a tenth anniversary reflection.

• DOI: 10.1016/j.surneu.2007.07.079
• 发表时间: 2007-11
• 期刊: Surgical neurology
• 作者: J. Grotta;J. Marler

Comprehensive stroke centers and the 'weekend effect': the SPOTRIAS experience.

• DOI: 10.1159/000345077
• 发表时间: 2012
• 期刊: Cerebrovascular diseases (Basel, Switzerland)
• 作者: Albright KC;Savitz SI;Raman R;Martin-Schild S;Broderick J;Ernstrom K;Ford A;Khatri R;Kleindorfer D;Liebeskind D;Marshall R;Merino JG;Meyer DM;Rost N;Meyer BC
• 通讯作者: Meyer BC

No consensus on definition criteria for stroke registry common data elements.

• DOI: 10.1159/000334146
• 发表时间: 2011-01
• 期刊: Cerebrovascular diseases extra
• 影响因子: 1.9
• 作者: Albright KC;Martin-Schild S;Bockholt HJ;Howard G;Alexandrov A;Alexandrov A;Sline MR;Grotta JC;Savitz SI
• 通讯作者: Savitz SI