Therapeutic Angiogenesis Using Human VEGF-A165/bFGF Plasmid Injected Percutaneously Into the Ischemic Myocardium of "No-option" Coronary Artery Disease Patients; Double-blind Placebo Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation at month 4 after injection therapy
研究概览
简要总结
Achieving therapeutic angiogenesis with gene therapy using a plasmid coding human VEGF-A165/bFGF injected into ischemic myocardium of refractory coronary artery disease patients, employing a percutaneous catheter-based technique- a double-blind placebo controlled study.
Some patients with persistent coronary artery disease cannot be effectively treated using methods available today ("no-option" patients). It is currently evident that an emerging therapy for them might be the stimulation of neoangiogenesis in the area of ischemic myocardium using growth factor genes. Agents attracting greatest interest are FGF (fibroblast growth factor) and VEGF (vascular-endothelial growth factor). A number of methods have been tested to deliver these agents to the area of interest.
Basic research has revealed that potent forms of angiogenic growth factors are the basic FGF (bFGF) and VEGF type A. Most clinical research on therapeutic angiogenesis is done using one of these two growth factors. This is to our knowledge the first clinical study using bicistronic VEGF-A 165/bFGF plasmid.
Patient population will comprise CCS III and CCS IV coronary artery disease patients who cannot be treated with standard revascularization methods. In the course of study we shall attempt to analyze the efficacy of therapeutic plasmid-induced angiogenesis in terms of myocardial perfusion increase and clinical symptom improvement. The feasibility and safety of plasmid delivery method will also be assessed. A percutaneous catheter-based technique (Myo-Star, Johnson & Johnson®) is used for plasmid delivery.
All patients enrolled will receive optimal medical treatment as judged by treating physician. An effort will be made to modify medical therapy during the study course only for clear reasons.
Standard angiography and ventriculography will be performed prior to plasmid injection therapy. Ischemic area of interest will be identified on inclusion by SPECT. Cardiac nuclear magnetic resonance (cNMR) with adenosine will also be performed to assess heart morphology, function and perfusion. Next, injections will be performed according to protocol.
Follow-up visits will be performed at month 4 and month 12 after injection therapy.
A change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation after injection therapy will be the primary measure of efficacy. Changes in exercise tolerance will also be monitored along with a number of other efficacy and safety parameters.
详细描述
Aim of the Study:
Achieving therapeutic angiogenesis with gene therapy using a plasmid coding human VEGF-A165/bFGF injected into ischemic myocardium of refractory coronary artery disease patients, employing a percutaneous catheter-based technique- a double-blind placebo controlled study.
A large group of patients with severe persistent symptoms of coronary artery disease cannot be effectively treated using the methods available today - they are sometimes described as "no-option" patients. It is currently evident that a promising emerging therapy for these patients might be the stimulation of neoangiogenesis in the area of ischemic myocardium, which generally requires the use of growth factors. Different methods and different growth factors have been used in experiments testing this approach. The two agents attracting the greatest interest of researchers are naturally FGF (fibroblast growth factor) and VEGF (vascular-endothelial growth factor). A number of methods, both in animal and human experiments, have also been tried to deliver these agents effectively to the area of interest and to ensure their prolonged action in target tissue.
Basic research has revealed that the most potent forms of angiogenic growth factors are the basic FGF (bFGF) and VEGF type A, especially in its 165 amino-acid form (VEGF-A 165) For this reason most clinical research on therapeutic angiogenesis is done using one of these two growth factors. This is to our knowledge the first clinical study using bicistronic VEGF-A 165/bFGF plasmid.
Study design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Severe (>= CCS III) ischemic heart disease despite optimal medical treatment in patients not amenable to percutaneous transluminal coronary angioplasty or coronary artery bypass surgery
- •Left ventricular ejection fraction >35%
- •Significant stress-induced reversible ischemic area documented on dipyridamole stress myocardial perfusion scintigraphy
- •Able to understand and willing to sign the informed consent
- •Older than 18 years of age
排除标准
- •Angina <CCS III
- •Secondary angina
- •Acute myocardial infarction within 4 weeks prior to inclusion
- •Diabetes with proliferative retinopathy
- •Diagnosed or suspected tumor
- •Chronic inflammatory or autoimmune disease
- •Fertile women
- •Left ventricular ejection fraction <35%
- •Patients not willing to or not able to give the informed consent to participate in the study
- •Patients with a severe disease (other than CAD) having life-expectancy below 1 year
结局指标
主要结局
Change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation at month 4 after injection therapy
时间窗: 4 months
次要结局
- Changes in exercise tolerance(month 4 and 12)
- Angiographic changes(4 months)
- Changes in life quality and patient's clinical condition(month 4 and 12)
- The occurrence of major cardiac adverse events (MACE) during long-term follow-up(throughout the 1-year follow-up)
- Serum VEGF-A165 and bFGF level(week 1,2,4,8)
- The occurrence of adverse events related to the plasmid administration procedure(Hospitalization related to procedure)
- occurrence of adverse events that may be related to overt VEGF or FGF activity(throughout the 1-year follow-up)