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: 6584685
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584685
• 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".

在西方世界，缺血性冠心病是发病率和死亡率的主要原因。大多数现有的治疗方法旨在通过减少心肌耗氧量来缓解症状，通过改变危险因素防止疾病的进一步发展，恢复动脉树的局部血流(PTCA或CABG)。治疗性血管生成可能通过为血流创造新的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来检测碱性成纤维细胞生长因子在人类缺血性心脏病中的治疗潜力，利用新的磁共振成像技术和Biosense机电标测确定临床血管生成研究的最佳结果指标，并在心肌缺血的动物模型中探索新的生长因子给药方法，包括心肌内给药和基因治疗。我们将在缺血性心脏病患者中进行治疗性血管生成的临床试验，这些患者是标准血管重建术的次佳候选者。这项试验将检验使用一种新的经皮心包内注射技术给予碱性成纤维细胞生长因子的血管生成效果。我们将通过负荷核素扫描研究bFGF治疗对临床参数、左心功能、冠脉造影术以及心肌缺血范围和程度的影响。Biosense NOGA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的结果变量，比较了这两种治疗策略。特别是，我们将验证两个新的结果衡量标准：磁共振成像和Biosense NOGA映射。最后，我们将在猪的慢性心肌缺血模型和小鼠的心肌梗死模型中开发新的给药策略，包括心肌内给药和基因治疗，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。这些新的给药策略，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具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，从临床试验，在动物模型中调查新的给药策略，以及为未来试验的进行开发标准化平台。这将导致一种治疗缺血性心脏病的新方法，并更好地理解生长因子和激光诱导的“血管生成”的机制。