Augusta SPAN 2

奥古斯塔 SPAN 2

• 批准号: 10591250
• 负责人: KRISHNAN M. DHANDAPANI
• 金额: $ 61.6万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-15 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591250
• 关键词: Acute; Adherence; Aging; Alteplase; Animal Model; Animals; Autologous; Blood flow; Circadian Rhythms; Clinical Trials; Clinical Trials Design; Clinical Trials Network; Collaborations; Data; Dedications; Development; Disabled Persons; Environment; FDA approved; Failure; Family suidae; Filament; Future; Human; Hyperglycemia; Inbred SHR Rats; Infarction; Intervention; Ischemic Stroke; Laboratories; Ligation; Magnetic Resonance Imaging; Manuscripts; Mentors; Methodology; Middle Cerebral Artery Infarction; Middle Cerebral Artery Occlusion; Modeling; Mus; National Institute of Neurological Disorders and Stroke; Network Infrastructure; Neuroprotective Agents; Obese Mice; Outcome; Patients; Performance; Pharmaceutical Preparations; Phase II Clinical Trials; Postdoctoral Fellow; Protocols documentation; Randomized, Controlled Trials; Rattus; Reporting; Research Personnel; Rodent; Scanning; Site; Stroke; System; Testing; Therapeutic; Training; Training and Infrastructure; Translations; Universities; acute stroke; animal imaging; behavior test; cerebroprotection; comorbidity; endovascular thrombectomy; experience; follow-up; functional outcomes; improved; medical schools; network models; neuroimaging; neuroprotection; next generation; novel therapeutics; outcome prediction; physiologic model; pre-clinical; pre-clinical assessment; randomized, clinical trials; single photon emission computed tomography; stroke model; stroke therapy; thrombolysis; training opportunity

Thrombolysis and endovascular thrombectomy (ET), remain the only two FDA-approved therapies for acute ischemic stroke. Despite the efficacy of ET, 50% of the patients remain disabled at 3 months. Adjunctive therapies to thrombolysis and ET are needed that provide “bridging neuroprotection” and improve collateral blood flow. Since presence of collaterals is a major predictor of outcome with ET, a promising new therapeutic avenue is development of “collateral therapeutics. Translation from the bench (rodent stroke models) to the bedside has been plagued by failure. The NINDS Stroke Preclinical Assessment Network (SPAN) has been an attempt to bridge this translational chasm using a multi-site preclinical randomized clinical trial (pRCT) network modeled after human clinical trials. The Medical College of Georgia/Augusta University was one of the 6 testing centers in SPAN 1. We were a high performing center as demonstrated by our consistent infarct size in the middle cerebral artery (MCA) occlusion model. SPAN 1 was successful and demonstrated feasibility with excellent protocol adherence, excellent data completion and low rates of animal loss in a large, multi-site preclinical network The Specific Aims for SPAN 2 include: Aim 1. Test up to 8 selected drugs/interventions in parallel, in collaboration with the Coordinating Center, NINDS and the other testing laboratories in the SPAN Network, in a multisite pRCT design to select the best cerebroprotective agent(s) for clinical trial in acute stroke. Aim 2. Assess short and long-term functional outcomes after experimental stroke, with a specific emphasis on neuroimaging and behavioral testing. Aim 3. As part of the SPAN Network, propose new ideas for sub-studies and manuscripts and develop a training pipeline for the next generation of preclinical stroke investigators. Expected impact: We will advance the most effective drug/intervention(s) into human clinical trial.

溶栓和血管内血栓切除术（ET）仍然是FDA批准的仅有的两种治疗急性血栓形成的方法。 缺血性中风尽管ET有效，但50%的患者在3个月时仍然残疾。辅助 需要溶栓和ET的治疗，提供“桥接神经保护”并改善侧支循环， 流由于侧支循环的存在是ET结局的主要预测因素，因此ET是一种有前途的新治疗途径， 是“络疗法”的发展。从实验台（啮齿动物中风模型）到床边的转换 被失败所困扰。NINDS卒中临床前评估网络（SPAN）一直试图 使用建模的多中心临床前随机临床试验（pRCT）网络弥合这一翻译鸿沟 在人体临床试验之后。 格鲁吉亚医学院/奥古斯塔大学是SPAN 1的6个测试中心之一。我们是一个高 表现中心，如我们在大脑中动脉（MCA）闭塞中的一致梗死面积所证明的 模型SPAN 1是成功的，并证明了具有出色的方案依从性和出色的数据的可行性 在大型多中心临床前网络中完成和降低动物损失率 SPAN 2的具体目标包括： 目标1。与NINDS协调中心合作，并行测试多达8种选定的药物/干预措施 和SPAN网络中的其他测试实验室，在多中心pRCT设计中选择最佳 用于急性中风临床试验的脑保护剂。 目标2.评估实验性卒中后的短期和长期功能结局，特别强调 神经成像和行为测试 目标3。作为SPAN网络的一部分，为子研究和手稿提出新的想法，并开展培训 下一代临床前中风研究者的管道。 预期影响：我们将推进最有效的药物/干预措施进入人体临床试验。