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: 6557141
• 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: 2001
• 资助国家: 美国
• 起止时间: 2001-04-03 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6557141
• 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，通过改变危险因素来防止疾病进一步进展，恢复局部动脉树段的血流（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。本研究的目的是研究碱性成纤维细胞生长因子（bFGF）在经皮心包内输送人类缺血性心脏病中的治疗潜力，利用新型磁共振成像技术和生物传感机电测绘技术确定临床血管生成研究的最佳结果指标，并探索新的生长因子在心肌缺血动物模型中的输送方法。包括心内输送和基因治疗。我们将在不适合标准血运重建策略的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。本试验将通过一种新的经皮棘骨下心包内给药技术来检验bFGF的血管生成效果。我们将研究bFGF治疗对临床参数、左心室功能、冠状动脉造影以及心肌缺血大小和程度的影响。在几个正在进行的临床血管生成研究和激光心肌血管重建术研究中比较这两种治疗策略的Biosense NOGA结果变量。特别是，我们将验证两种新的结果测量：磁共振成像和Biosense NOGA制图。最后，我们将在猪慢性心肌缺血模型和小鼠基质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血管生成的蛋白质和基因治疗策略。这些新的递送策略，如果成功，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项目，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，动物模型中新型给药策略的研究，以及为未来试验进行的标准化平台的开发。这将为缺血性心脏病的治疗提供一种新的方法，并更好地了解生长因子和激光诱导的“血管生成”的机制。