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 批准的仅有的两种急性发作疗法 尽管 ET 有效，但 50% 的患者在 3 个月后仍然无法使用。 需要溶栓和 ET 疗法来提供“桥接神经保护”并改善侧支血 由于侧支循环的存在是 ET 结果的主要预测因素，因此这是一种有前途的新治疗途径。 正在开发“并行疗法”，从实验室（啮齿动物中风模型）到临床。 NINDS 中风临床前评估网络 (SPAN) 一直受到失败的困扰。 使用多中心临床前随机临床试验 (pRCT) 网络建模来弥合这一转化鸿沟 经过人体临床试验后。 佐治亚医学院/奥古斯塔大学是 SPAN 1 的 6 个测试中心之一。我们是一个高 大脑中动脉 (MCA) 闭塞处梗塞面积一致，证明了执行中心的有效性 SPAN 1 模型取得了成功，并通过出色的协议遵守性和出色的数据证明了可行性。 大型多地点临床前网络的完成度和动物损失率低 SPAN 2 的具体目标包括： 目标 1. 与 NINDS 协调中心合作，并行测试最多 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 设计中选择最佳的 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果，特别强调 神经影像和行为测试。 目标 3. 作为 SPAN 网络的一部分，提出子研究和手稿的新想法并开发培训 下一代临床前卒中研究人员的管道。 预期影响：我们将把最有效的药物/干预措施推进人体临床试验。