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）仍然是仅有的两种急性FDA批准的疗法 缺血性中风。尽管ET的效率是ET的效率，但有50％的患者在3个月时仍残疾。辅助性 需要对溶栓和ET进行疗法，以提供“桥接神经保护”并改善附带血液 流动。由于conteratras的存在是ET结果的主要预测指标，这是一个有希望的新的治疗途径 是“ Collat​​ell疗法的发展。 失败困扰。 Ninds中风临床前评估网络（SPAN）一直是尝试 桥梁使用多站点的临床前随机临床试验（PRCT）网络进行翻译的鸿沟 经过人类临床试验。 佐治亚州/奥古斯塔大学医学院是SPAN 1的6个测试中心之一。我们很高 表现中心，如我们在中部动脉（MCA）闭塞中一致的梗塞大小所证明的 模型。 SPAN 1成功，并具有出色的协议依从性，出色的数据，证明了可行性 大型多站点临床前网络中动物损失的完成和低率 跨度2的具体目标包括： AIM 1。与协调中心合作，最多测试8种选定的药物/干预措施 以及SPAN网络中的其他测试实验室，在多站点PRCT设计中，以选择最佳 急性中风临床试验的脑保护剂。 AIM 2。在实验中风后评估短期和长期功能结果，并特别强调 神经影像学和行为测试。 目标3。作为SPAN网络的一部分，提出了针对子研究和手稿的新想法，并开发了培训 下一代临床前中风研究人员的管道。 预期影响：我们将把最有效的药物/干预措施推向人类临床试验。