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率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需氧量来缓解症状，通过改变风险因素来防止疾病进一步进展，恢复动脉树局部段的血流（PTCA或CABG）。治疗性血管生成可以通过创造新的血流场所来恢复缺血心肌的血流。本研究的目的是通过经皮心包内给药研究碱性成纤维细胞生长因子（bFGF）在人类缺血性心脏病中的治疗潜力，使用新型磁共振成像技术和Biosense机电标测确定临床血管生成研究的最佳结局指标，并探索心肌缺血动物模型中新型生长因子给药方法，包括心肌内递送和基因治疗。我们将在缺血性心脏病患者中进行一项治疗性血管生成的临床试验，这些患者是标准血运重建策略的次优候选人。本试验将检查使用一种新的经皮剑突下心包内递送技术给予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负荷核灌注扫描对心肌缺血的大小和程度的影响。比较这两种治疗策略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的Biosense NOGA结局变量。特别是，我们将验证两个新的结果措施：磁共振成像和Biosense NOGA映射。最后，我们将在猪慢性心肌缺血模型和小鼠基质胶和梗死模型中开发新的递送策略，包括心肌内递送和基因治疗，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。这些新的输送策略，如果成功的话，将进行临床研究。这些相互关联的项目构成了一个有凝聚力的研究计划，旨在阐明治疗性血管生成的各个方面。尽管我们希望解决这个问题，但所涉及的技术必然是广泛的，包括临床试验，动物模型中新的递送策略的研究，以及为未来试验的进行开发标准化平台。这将为缺血性心脏病的治疗提供一种新的方法，并使人们更好地理解生长因子和激光诱导的“血管生成”机制。