The NIH SPAN Coordinating Center

NIH SPAN 协调中心

基本信息

批准号：
10224355
负责人：
Patrick D Lyden
金额：
$ 78.29万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224355
关键词：
Acute Address Alteplase Animal Model Animals Appearance Award Awareness Back Behavior Behavioral Blinded Cerebral hemisphere hemorrhage Clinical Clinical Trials Coagulation Process Consultations Data Databases Development Doctor of Philosophy Evaluation Failure Federal Government Funding Futility Future Goals Government Grouping Hemorrhage Histologic Histology Human Image Individual Industry Infrastructure Ischemia Ischemic Stroke Knowledge Laboratories Lead Leadership Lesion Masks Measures Middle Cerebral Artery Occlusion Modeling Mus National Institute of Neurological Disorders and Stroke Neuroprotective Agents Oryctolagus cuniculus Outcome Outcome Assessment Personal Communication Phase Preclinical Testing Procedures Production Quality Control Rattus Reperfusion Therapy Research Personnel Scanning Secure Site Specific qualifier value Stroke System Talents Testing Thrombectomy Time Training United States National Institutes of Health arm base behavior test behavioral outcome cost cost efficient design drug testing experience flexibility improved outcome industry partner innovation neuroimaging neuroprotection novel novel strategies phase 2 testing pre-clinical pre-clinical assessment preclinical development preclinical study primary outcome programs secondary outcome stroke model stroke patient stroke recovery stroke therapy success symposium therapy design thrombolysis

项目摘要

We propose a novel, adaptive, secured system for parallel testing of promising interventions designed to improve outcome compared to reperfusion alone with thrombolysis, thrombectomy or both. The applicant PI and collaborators together have decades of experience using preclinical animal stroke models. Also, and perhaps uniquely, the applicant PI and collaborators have led clinical trial coordinating centers for large and small multi‐center and single center Phase 1, 2, and 3 clinical trials on behalf of the Federal Government and various industry partners. Thus, by combining decades of experience and expertise in animal modeling with clinical trial management this application affords NINDS an opportunity to significantly enhance the likelihood that SPAN will guide the selection of the best agent(s) to transition to future clinical trials likely to be conducted through StrokeNet. The applicant PI and collaborators are aware of, and have participated in, many reviews and symposia detailing the significant failures of previous preclinical stroke development. A plethora of putative neuroprotectants proceeded to clinical trial based on favorable preclinical assessment, only to fail in subsequent clinical trials of human stroke patients. The plethora of clinical failures has cost industry and governments hundreds of millions of dollars and wasted the time, talent, and effort of hundreds of investigators and coordinators. The recent successful development of thrombectomy for acute ischemic stroke generated considerable enthusiasm for re‐testing compounds in combination with thrombectomy. Thus, SPAN is intended to screen and select highly promising candidate treatments for possible study in StrokeNet. A success in SPAN will provide a significant impetus to renew efforts toward successful clinical deployment of novel, promising neuroprotectants. In the past 5 years, two significant developments raise new hope for neuroprotection: the appearance of compounds with multiple mechanisms of action, and the promulgation of new standards for the rigorous preclinical development of stroke treatment candidates. The SPAN effort affords the highly significant opportunity to find a promising candidate treatment, test it in StrokeNet, and then back‐validate the ideal preclinical testing paradigm that predicts success in clinical trials. This present application, if funded, will achieve significant improvement and advancement of preclinical development by implementing critical technical innovations. The state‐of‐the‐art technical solution offered by our collaborator, the Laboratory of Neuroimaging (LONI) is secure, robust, reliable, and ready to implement immediately because Drs. Lyden and Toga collaborated during RHAPSODY to provide sites a turn‐key solution for uploading images (www.LONI.usc.edu). We also propose the highly novel use of distributed, masked evaluation. This novel approach allows for a secure, blinded, cost efficient, with built in central quality‐control.

我们提出了一种新颖的、适应性的、安全的系统，用于平行测试有前景的干预措施，与单独的再灌注和溶栓、血栓切除术或两者相比，可以改善结果。独特的是，申请人的 PI 和合作者代表联邦政府和各个行业合作伙伴领导了大型和小型多中心和单中心 1 期、2 期和 3 期临床试验的临床试验协调中心。凭借在动物建模和临床试验管理方面的经验和专业知识，该应用程序为 NINDS 提供了一个机会，可以显着提高 SPAN 指导选择最佳药物以过渡到可能通过 StrokeNet 进行的未来临床试验的可能性。合作者了解并参与了许多详细介绍先前临床前中风发展的重大失败的评论和研讨会。基于有利的临床前评估，大量假定的神经保护剂进入了临床试验，但结果却是这样。在随后的人类中风患者临床试验中，大量的临床失败给行业和政府带来了数亿美元的损失，并浪费了数百名研究人员和协调员的时间、人才和精力。中风引起了人们对重新测试化合物与血栓切除术相结合的极大热情，因此，SPAN 旨在为 StrokeNet 的可能研究筛选和选择高度有前途的候选治疗方法，这将为重新努力实现成功的临床部署提供重要动力。在过去的 5 年里，两项重大进展为神经保护带来了新的希望：具有多种作用机制的化合物的出现，以及针对中风治疗候选药物的严格临床前开发的新标准的颁布。提供了一个非常重要的机会来寻找有前途的候选治疗方法，在 StrokeNet 中对其进行测试，然后对预测临床试验成功的理想临床前测试范例进行回溯验证。如果获得资助，本申请将实现显着的改进和进步。我们的合作者神经影像实验室 (LONI) 提供的最先进的技术解决方案安全、稳健、可靠，并且可以立即实施，因为 Lyden 和 Toga 博士合作。在 RHAPSODY 期间，我们为站点提供了上传图像的统包解决方案（www.LONI.usc.edu）。我们还提出了高度分布式、屏蔽评估的新颖方法，这种新颖的方法可以实现安全、盲目的成本。高效，内置中央质量控制。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cerebroprotection for Acute Ischemic Stroke: Looking Ahead.

DOI：
10.1161/strokeaha.121.032241
发表时间：
2021-08
期刊：
Stroke
影响因子：
8.3
作者：
Lyden PD
通讯作者：
Lyden PD

Top Priorities for Cerebroprotective Studies-A Paradigm Shift: Report From STAIR XI.

DOI：
10.1161/strokeaha.121.034947
发表时间：
2021-08
期刊：
Stroke
影响因子：
8.3
作者：
Lyden P;Buchan A;Boltze J;Fisher M;STAIR XI Consortium*
通讯作者：
STAIR XI Consortium*

Magnetic Resonance Vessel Wall Imaging in Central Nervous System Vasculitides: A Case Series.

DOI：
10.1097/nrl.0000000000000298
发表时间：
2020-11
期刊：
The neurologist
影响因子：
0
作者：
Padrick MM;Maya MM;Fan Z;Szumski N;Lyden PD;Song SS;Dumitrascu OM
通讯作者：
Dumitrascu OM

Post-Traumatic Cerebral Infarction: A Narrative Review of Pathophysiology, Diagnosis, and Treatment.

DOI：
10.3390/neurolint16010006
发表时间：
2024-01-04
期刊：
Neurology international
影响因子：
3
作者：
Poblete RA;Zhong C;Patel A;Kuo G;Sun PY;Xiao J;Fan Z;Sanossian N;Towfighi A;Lyden PD
通讯作者：
Lyden PD

3K3A-Activated Protein C Variant Does Not Interfere With the Plasma Clot Lysis Activity of Tenecteplase.

3K3A 激活的蛋白 C 变体不会干扰替奈普酶的血浆凝块溶解活性。

DOI：
10.1161/strokeaha.120.028793
发表时间：
2020
期刊：
Stroke
影响因子：
8.3
作者：
Mukherjee,Purba;Lyden,Patrick;Fernández,JoséA;Davis,ThomasP;Pryor,KentE;Zlokovic,BerislavV;Griffin,JohnH
通讯作者：
Griffin,JohnH