ADENOVIRUS MEDIATED VEGF121 CDNA MYOCARDIAL ANGIONGENESI

腺病毒介导的 VEGF121 CDNA 心肌血管生成

• 批准号: 6668358
• 负责人: Todd K Rosengart
• 金额: $ 19.94万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668358
• 关键词: angiogenesis; biotechnology; clinical research; clinical trial phase I; cooperative study; coronary disorder; gene therapy; heart circulation; heart revascularization; human subject; human therapy evaluation; magnetic resonance imaging; nonsurgical revascularization; single photon emission computed tomography; vascular endothelial growth factors

Angioplasty-stents and coronary artery bypass grafting remain the primary interventional therapies for the treatment of coronary artery disease CAD, but these treatments remain limited by recurrent disease, significant associated morbidities and mortality, and the failure of these "mechanical" techniques to treat diffuse and small vessel disease. Gene therapy for angiogenesis describes an alternative revascularization strategy whereby angiogenic genes are delivered to ischemic tissues for the purpose for inducing neovascularization. To avoid the limitations of patients acting as their own controls used in previous clinical trials examining this therapy for the treatment of CAD, we designed a prospective placebo controlled, blinded, randomized phase I/II trial to examine the consequence of adenovirus (Ad) vector-mediated myocardial transfer of the human vascular endothelial growth factor 121 cDNA (Ad/CU/VEGF121.1), as compared to saline injection, as an adjunct in individuals undergoing "off-pump" coronary artery bypass (OPCAB) grafting to the left anterior descending +/- the right coronary artery. The Ad/CU/VEGF121.1 vector (10/9 particle units in 30, 100 1 aliquots_ or saline will be administered to the circumflex distribution. The underlying hypothesis is that direct administration to the myocardium of Ad/CU/VEGF121.1 is safe and improves cardiac perfusion and function. This randomized, blinded, placebo controlled study design, in which angiogenic gene therapy is delivered in a consistent fashion and assessed by exercise testing, sestamibi SPECT scanning, and MRI without the potential toxicity induced by cardiopulmonary bypass, should allow the assessments of the two specific hypotheses: (1) there are no adverse effects in administering the Ad/CU/VEGF121.1 vector in this fashion: and (2) there are global and/or regional improvements in cardiac perfusion and function associated with Ad/CU/VEGF121.1 therapy. Because the study design is prospective, placebo controlled, blinded and randomized, the results should help determine whether larger trials of this therapy are warranted.

血管成形术-支架和冠状动脉旁路移植术仍然是治疗冠状动脉疾病CAD的主要介入治疗方法，但这些治疗方法仍然受到复发疾病、显著相关发病率和死亡率以及这些“机械”技术在治疗弥漫性和小血管疾病方面的失败的限制。血管生成的基因治疗描述了一种替代的血管重建策略，通过将血管生成基因输送到缺血组织以诱导新生血管的目的。我们设计了一项前瞻性的安慰剂对照的随机I/II期试验，以避免在研究这种疗法治疗冠心病的临床试验中患者作为自身对照的局限性，我们设计了一项前瞻性的安慰剂对照、随机I/II期试验，以观察腺病毒(Ad)载体介导的人血管内皮生长因子121基因(Ad/CU/VEGF121.1)作为辅助手段在接受左前降支+/-右冠状动脉“非体外循环”冠状动脉旁路移植术(OPCAB)的患者中的效果。将Ad/CU/VEGF121.1载体(30,100 1等分或生理盐水中的10/9颗粒单位)施加于回旋分布。其基本假设是，直接将Ad/CU/VEGF121.1注射到心肌是安全的，并且可以改善心脏的血流灌注和功能。这项随机、盲目、安慰剂对照研究设计以一致的方式进行血管生成基因治疗，并通过运动试验、Sestamibi SPECT扫描和核磁共振成像(MRI)进行评估，没有体外循环引起的潜在毒性，应可对两个特定假设进行评估：(1)以这种方式应用Ad/CU/VEGF121.1载体没有不良反应：(2)与Ad/CU/VEGF121.1治疗相关的心脏灌注和功能有全球和/或区域性的改善。因为这项研究设计是前瞻性的、安慰剂对照的、盲目的和随机的，结果应该有助于确定是否有必要进行更大规模的治疗试验。