Clinical trials of local percutaneous delivery of bFGF in CAD

bFGF 局部经皮递送治疗 CAD 的临床试验

• 批准号: 6320229
• 负责人: ROGER J LAHAM
• 金额: $ 21.93万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6320229
• 关键词: angiogenesis; cardiovascular disorder chemotherapy; clinical research; clinical trial phase I; coronary disorder; drug administration routes; drug delivery systems; fibroblast growth factor; heart function; human subject; human therapy evaluation; intraluminal angioplasty; laboratory mouse; laser therapy; magnetic resonance imaging; myocardial ischemia /hypoxia; pericardium; swine

Ischemic coronary disease is the leading cause of morbidity and mortality in the Western world. Most available therapeutic approaches aim either at relieving symptoms by reducing myocardial oxygen demand, preventing further disease progression by modifying risk factors, restoring flow to a localized segment of the arterial tree (PTCA or CABG). Therapeutic angiogenesis may restore flow to the ischemic myocardium by creating new venues for blood flow. The purpose of the present investigation will be to examine the therapeutic potential of basic fibroblast growth factor (bFGF) in human ischemic heart disease using percutaneous intrapericardial delivery, define optimal outcome measures for clinical angiogenesis studies using a novel magnetic resonance imaging technique and Biosense electromechanical mapping, and explore novel growth factor deliver methods in animal models of myocardial ischemia, including intramyocardial delivery and gene therapy. We will conduct a clinical trial of therapeutic angiogenesis in patients with ischemic heart disease who are suboptimal candidates for standard revascularization strategies. This trial will examine the angiogenic efficacy of bFGF administered using a novel percutaneous subxyphoid intrapericardial delivery technique. We will investigate the effects of bFGF treatment on clinical parameters, left ventricular function, coronary angiography, and on the size and extent of myocardial ischemia using stress nuclear perfusion scans. Biosense NOGA outcome variables in several ongoing clinical angiogenesis studies and laser myocardial revascularization studies comparing these two treatment strategies. In particular, we will validate two novel outcome measures: magnetic resonance imaging and Biosense NOGA mapping. Finally, we will develop novel delivery strategies in a porcine model of chronic myocardial ischemia and mouse matrigel and infarction models including intramyocardial delivery and gene therapy, and compare protein and gene therapy strategies for growth factor-induced angiogenesis. These novel delivery strategy, if successful, will be investigated clinically. These interrelated projects constitute a cohesive research program aimed at elucidating various aspects of therapeutic angiogenesis. Even though the problem, we wish to address, the techniques involved are necessarily broad, ranging from clinical trials, investigation of novel delivery strategies in animal models, and development of a standardized platforms for the conduction of future trials. This should lead to a novel approach to the treatment of ischemic heart disease and a better understanding of the mechanisms of growth- factor and laser induced "angiogenesis".

缺血性冠状动脉疾病是西方世界发病和死亡率的主要原因。大多数可用的治疗方法旨在通过减少心肌氧的需求来缓解症状，从而通过改变危险因素来防止进一步的疾病进展，从而恢复流向动脉树（PTCA或CABG）的局部段。治疗性血管生成可以通过创建血流的新场所来恢复流向缺血性心肌的流动。本研究的目的是使用经皮内递送在人缺血性心脏病中检查基本成纤维细胞生长因子（BFGF）的治疗潜力，并使用新型的磁性复位技术和生物浓度的电子力学图像来定义临床血管生成研究的最佳结果测量，并探索新的生长因子在心肌缺血模型（包括心脏内分娩和基因疗法）中的动物模型中的方法。我们将对缺血性心脏病患者进行治疗性血管生成的临床试验，他们是标准血运重建策略的次优候选者。该试验将检查使用新型经皮下脑膜内递送技术给予BFGF的血管生成功效。我们将研究BFGF治疗对临床参数，左心室功能，冠状动脉造影以及使用应力核灌注扫描的大小和程度的影响。在进行的几项正在进行的临床血管生成研究和激光心肌血运重建研究中，Biosense NOGA结果变量比较了这两种治疗策略。特别是，我们将验证两种新的结果指标：磁共振成像和生物素型NOGA映射。最后，我们将在慢性心肌缺血和小鼠基质的猪模型中制定新的分娩策略以及包括心脏内递送和基因治疗的梗塞模型，并比较生长因子诱导的血管生成的蛋白质和基因治疗策略。如果成功的话，这些新颖的交付策略将在临床上进行研究。这些相互关联的项目构成了一个凝聚力研究计划，旨在阐明治疗性血管生成的各个方面。即使我们希望解决这个问题，涉及的技术一定是广泛的，从临床试验，对动物模型中的新型交付策略进行调查以及开发标准化平台以进行未来试验的发展。这应该导致一种新的方法来治疗缺血性心脏病，并更好地理解生长因子和激光诱导的“血管生成”的机制。