Safety of tPA plus Transcranial Emission of Low-Energy Laser for Acute Stroke

tPA 联合低能量激光经颅发射治疗急性中风的安全性

• 批准号: 8267651
• 负责人: Justin Allen Zivin
• 金额: $ 66.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-19 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8267651
• 关键词: Adverse effects; Alteplase; Animals; Behavioral; Blood flow; Brain; Brain Embolism; Brain Injuries; Cerebral Ischemia; Cerebral hemisphere hemorrhage; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Coagulation Process; Data; Disease; Dose; Effectiveness; Electromagnetic Energy; Embolism; FDA approved; Human; Infrared Rays; International; Intravenous; Investigation; Lasers; Modality; Modeling; Monitor; Nervous System Physiology; Oryctolagus cuniculus; Outcome; Patients; Phase II Clinical Trials; Phase III Clinical Trials; Principal Investigator; Recovery of Function; Resolution; Roentgen Rays; Safety; Series; Skin; Solid; Solid Neoplasm; Stroke; Symptoms; TNFRSF5 gene; Therapeutic; Thrombolytic Therapy; Time; Tissues; acute stroke; bone; cost effective; design; irradiation; neuroprotection; preclinical study; research study; safety testing; stroke recovery; stroke therapy; thrombolysis

There is evidence that low-energy infrared laser irradiation (LELI) can modify a number of disease states, and in preclinical and clinical studies we have developed preliminary data showing that stroke is among them. Since intravenous tissue plasminogen activator (tPA) is currently the only FDA-approved treatment for acute stroke, but increases the absolute rates of resolution of symptoms only from 25% to 38%, there is need for additional therapeutic modalities to further contain or eliminate brain damage. We have developed a series of animal cerebral ischemia and hemorrhage models that, when used in a coordinated fashion, should help identify many of the important variables in LELI that pertain to its viability, safety, and efficacy as an adjunctive therapy to thrombolysis. Toward this end, this project is designed to achieve the following specific aims: (1) Examine the interaction of LELI with tPA therapy using a rabbit small clot brain embolism model (SCEM), which allows monitoring of a behavioral endpoint. This approach should yield information that helps to predict the clinical outcome of LELI combined with tPA in humans. The study also examines whether there is any effect of LELI on tPA-induced intracerebral hemorrhaging in the large clot embolism model (LCEM), which will serve to warn or reassure clinical investigators about the potential of LELI side effects in stroke victims. (2) Conduct a phase II clinical trial to test safety and preliminarily assess efficacy of LELI in combination with tPA with acute stroke patients. One approach to stroke therapy, in addition to thrombolysis, is to provide some form of neuroprotection immediately after stroke onset to reduce the damage caused by lack of blood flow and increase the window of opportunity for thrombolytic therapy. A second strategy is to administer neuroprotection after initiation of thrombolysis to reduce damage while thrombolysis is occurring. A third is to induce neuroprotection after thrombolysis is complete to salvage tissue that would otherwise die even though blood flow has been restored. Finally, it would be useful to develop strategies to produce recovery of function that may restore at least some neurological function. LELI is potentially capable of producing all of these effects. The potential impact of the study results on acute stroke therapeutics is thus far-reaching.

有证据表明低能量红外激光照射 (LELI) 可以改变多种疾病状态， 在临床前和临床研究中，我们已经开发出初步数据，表明中风就是其中之一。 由于静脉注射组织纤溶酶原激活剂 (tPA) 是目前 FDA 批准的唯一治疗急性 中风，但仅将症状的绝对缓解率从 25% 提高到 38%，因此需要 进一步遏制或消除脑损伤的额外治疗方式。我们开发了一系列 动物脑缺血和出血模型，当以协调的方式使用时，应该会有所帮助 确定 LELI 中与其作为辅助疗法的可行性、安全性和有效性相关的许多重要变量 治疗以溶栓为主。为此，本项目旨在实现以下具体目标：（1） 使用兔小血栓脑栓塞模型 (SCEM) 检查 LELI 与 tPA 治疗的相互作用， 它允许监控行为端点。这种方法应该产生有助于预测的信息 LELI 联合 tPA 在人类中的临床结果。该研究还检验了是否存在任何 LELI 对大血栓栓塞模型 (LCEM) 中 tPA 诱导的脑出血的影响，这将 旨在警告或安抚临床研究人员 LELI 对中风患者可能产生的副作用。 (2) 开展II期临床试验，测试LELI联合tPA的安全性并初步评估疗效 与急性中风患者。 除了溶栓之外，中风治疗的一种方法是提供某种形式的神经保护 中风发作后立即减少因血流不足造成的损害并增加治疗窗口 溶栓治疗的机会。第二种策略是在开始后进行神经保护 溶栓以减少溶栓过程中的损害。第三是诱导神经保护 溶栓治疗已完成，以挽救即使血流已恢复也会死亡的组织。 最后，制定能够恢复功能的策略将是有用的，这些功能至少可以恢复一些功能。 神经功能。 LELI 有可能产生所有这些效果。的潜在影响 因此，急性中风治疗的研究结果具有深远的意义。