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.

我们提出了一种新型，自适应，有安全的系统，用于对旨在改善预后的承诺干预措施并行测试，与仅通过溶栓，血栓切除术或两者兼而有之。适用的PI和合作者共同使用临床前动物中风模型拥有数十年的经验。此外，也许是独特的，适用的PI和合作者领导了代表联邦政府和各个行业合作伙伴的大型和小型中心和单个中心1、2和3临床试验的临床试验协调中心。通过将数十年的动物建模经验和专业知识与临床试验管理结合起来，该应用程序可以显着增强SPAN的可能性，以指导最佳药物的选择，以过渡到可能通过Stromentet进行的未来临床试验。 PI和合作者的应用程序意识到并参与了许多评论和座谈会，详细介绍了先前的临床前中风开发的重大失败。基于有利的临床前评估，大量推定的神经保护剂进行了临床试验，但在随后的人类中风患者的临床试验中失败。众多的临床失败具有成本行业和政府数亿美元的成本，浪费了数百名调查人员和协调员的时间，才华和精力。急性缺血性中风的血栓切除术的最新成功开发产生了重新测试化合物与血栓切除术结合的考虑因素。跨度旨在筛选并选择高度有希望的候选治疗方法，以便在Strokenet中进行研究。成功的跨度将为成功的临床部署提供新的，有希望的神经保护剂的临床部署。在过去的5年中，两个重大的发展引起了神经保护的新希望：具有多种作用机理的化合物的出现，以及颁布新标准的新标准，以严格的临床前培养候选者。 SPAN的努力为找到有前途的候选治疗，在Strokenet中进行测试，然后进行后测量的理想临床前测试范式，以预测临床试验中的成功。本应用程序（如果资助）将通过实施关键的技术创新来实现临床前开发的重大改进和进步。我们的合作者神经影像学实验室（LONI）提供的最先进的技术解决方案是安全，健壮，可靠的，并且由于DRS而准备立即实施。 Lyden和Toga在Rhapsody期间合作，为站点提供了用于上传图像的交钥匙解决方案（www.loni.usc.edu）。我们还提出了对分布式，掩盖评估的高度新颖使用。这种新颖的方法允许使用中央质量控制的安全，盲目，具有成本效益。

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