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: 8377343
• 负责人: Justin Allen Zivin
• 金额: $ 63.03万
• 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/8377343
• 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，低能红外激光照射（LELI）可以改变许多疾病状态， 在临床前和临床研究中，我们制定了初步数据，表明中风就是其中之一。 由于静脉内组织纤溶酶原激活剂（TPA）目前是FDA批准的急性治疗方法 中风，但只有25％增加到症状的绝对率，需要 进一步遏制或消除脑损伤的其他治疗方式。我们已经开发了一系列 动物脑缺血和出血模型，当以协调方式使用时，应有助于 确定LELI中许多与其生存能力，安全性和功效有关的重要变量 治疗溶栓。为此，该项目旨在实现以下特定目标：（1） 使用兔子小凝块脑栓塞模型（SCEM），检查LELI与TPA治疗的相互作用， 这允许监视行为终点。这种方法应产生有助于预测的信息 Leli的临床结果与人类的TPA结合。该研究还检查了是否有 LELI对大凝块栓塞模型（LCEM）中TPA诱导的脑出血的影响，这将 发出警告或保证临床研究人员有关中风受害者Leli副作用的潜力。 （2） 进行II期临床试验，以测试安全性并初步评估LELI与TPA结合的功效 与急性中风患者。 除溶栓外，一种中风治疗的一种方法是提供某种形式的神经保护作用 中风发作后立即减少由于缺乏血流而造成的损害，并增加 溶栓疗法的机会。第二种策略是在开始后进行神经保护 溶栓以减少溶栓时减少损伤。三分之一是在 溶栓完全是挽救组织，即使血流恢复了，溶出组织也会死亡。 最后，制定策略以产生功能的恢复将是有用的 神经功能。 Leli有可能产生所有这些影响。潜在的影响 因此，有关急性中风治疗的研究结果是深远的。