MULTICENTER SPINAL CORD INJURY STUDY

多中心脊髓损伤研究

• 批准号: 3418889
• 负责人: WISE YOUNG
• 金额: $ 111.35万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3418889
• 关键词: antioxidants; disease /disorder model; dosage; drug addiction antagonist; drug administration rate /duration; drug metabolism; drug screening /evaluation; excitatory aminoacid; gender difference; histopathology; hormone therapy; inhibitor /antagonist; laboratory rat; methylprednisolone; narcotic antagonists; nervous system disorder chemotherapy; nonhuman therapy evaluation; peptide hormone analog; pregnane compound; spinal cord injury; thyrotropin releasing hormone

The second National Acute Spinal Cord Injury Study (NASCIS 2) showed that methylprednisolone (MP) improved neurologic recovery in human spinal cord injury (SCI) but the treatment has a strictly limited therapeutic window. To identify better treatments, laboratories must now evaluate different doses, times, and durations of therapy along and combined with MP, and at several injury levels. Investigation of all these variable requires thousands of experiments, beyond the capabilities of any individual laboratory. Many promising treatments now await such pre-clinical investigation. Systematic pre-clinical data allow rational design treatment protocols. Arbitrary treatment protocols have a high risk of false negatives. A Multicenter Animal Spinal Cord Injury Study (MASCIS) is therefore proposed. Eight leading SCI laboratories will participate: New York University, Ohio State University, Washington University, University of Cincinnati, University of California at San Francisco, Medical University of South Carolina, Georgetown University, A. I. duPont Institute. Data analysis will be carried out at Yale University. The centers will use the same SCI model and outcome measures to study 5 neuroprotective agents: MP (glucocorticoid), YM-14673 thyrotropin releasing hormone analog), tirilazad mesylate (a 21-aminosteroid), nalmefene (a kappa- selective opioid receptor blocker), and excitatory amino acid receptor blockers. MASCIS will annually examine acute (24h) and chronic (6w) outcomes of 1600 rats subjected to 3 standardized grades of SCI and treated with 2-3 different doses of the drugs started at 0.5h, 6h, or 12h after injury, continued for 6h or 24h, alone and combined with MP. Plasma and tissue drug levels will be measured at 2-24h. Acute lesion volumes will be measured at 24h. Injury conditions will be carefully monitored and controlled. Acute lesion volumes, behavioral recovery, and different histologic outcome measures will be compared. This work will provide detailed and systematic pre-clinical data for acute SCI treatments, allowing rationale design of treatment protocols. MASCIS is the first proposal of a multicenter pre-clinical trial on this scale and will establish a needed precedent for similar studies in stroke and traumatic brain injury.

第二项全国急性脊髓损伤研究（NASCIS 2）表明 甲基强酮（MP）改善了人脊髓的神经系统恢复 受伤（SCI），但治疗的治疗窗口严格有限。 为了确定更好的治疗方法，实验室现在必须评估不同的治疗方法 治疗的剂量，时间和持续时间与MP一起，并与MP结合 在几个伤害水平上。 对所有这些变量的调查需要 数千个实验，超出任何个人的能力 实验室。 现在有许多有前途的治疗方法正在等待这样的临床前 调查。 系统的临床前数据允许合理设计 治疗方案。 任意治疗方案的高风险 假否定。 因此，多中心动物脊髓损伤研究（MASCIS）是 建议的。 八个领先的SCI实验室将参加：纽约 俄亥俄州立大学，华盛顿大学，大学 辛辛那提，加利福尼亚大学旧金山大学医科大学 南卡罗来纳州，乔治敦大学，A。I。杜邦学院。 数据 分析将在耶鲁大学进行。 中心将使用 相同的SCI模型和研究结果测量5神经保护 代理：MP（糖皮质激素），YM-14673甲状腺激素释放激素 类似物），蒂里拉萨德梅赛酸盐（21-氨基类固醇），纳米芬（kappa-- 选择性阿片类药物受体阻滞剂）和兴奋性氨基酸受体 阻滞剂。 Mascis每年将检查急性（24h）和慢性（6W）结果 1600只大鼠接受3个标准化等级的SCI，并用2-3治疗 受伤后的0.5h，6h或12h开始，不同剂量的药物开始 持续6小时或24小时，单独使用MP。 血浆和组织 药物水平将在2-24H时测量。 急性病变量将是 测量在24小时。 伤害条件将仔细监测，并 受控。 急性病变体积，行为恢复和不同 将比较组织学结果指标。 这项工作将提供 急性SCI治疗的详细和系统的临床前数据， 允许对治疗方案的理由设计。 Mascis是第一个 在此规模上进行多中心临床前试验的提议，并将 为中风和创伤的类似研究建立所需的先例 脑损伤。