The Effects of Autologous Intracoronary Stem Cell Transplantation In Patients With End-Stage Dilated Cardiomyopathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Heart Failure Mortality
研究概览
简要总结
Several studies have documented that transplantation of bone marrow-derived cells (BMC) following acute myocardial infarction is associated with a reduction in infarct scar size and improvements in left ventricular function and perfusion. The available evidence in humans suggests that BMC transplantation is associated with improvements in physiologic and anatomic parameters in both acute myocardial infarction and chronic ischemic heart disease, above and beyond the conventional therapy. In particular, intracoronary application of BMC is proved to be safe and was associated with significant improvement in the left ventricular ejection fraction (LVEF) in patients with chronic heart failure.
In contrast to ischemic heart failure, the data on effects of BMC transplantation in patients with dilated cardiomyopathy are limited to pre-clinical studies. In a rat model of dilated cardiomyopathy, intramyocardial delivery of pluripotent mesenchymal cells improved LVEF, possibly through induction of myogenesis and angiogenesis, as well as by inhibition of myocardial fibrosis, suggesting that the beneficial effects of stem cell transplantation in dilated cardiomyopathy may primarily be related to their ability to supply large amounts of angiogenic, antiapoptotic, and mitogenic factors. Similarly, transplantation of cocultured mesenchymal stem cells and skeletal myoblasts was shown to improve LVEF in a murine model of Chagas disease.
Study Aim:
To define the clinical effects of BMC transplantation in dilated cardiomyopathy in a pilot clinical study investigating the effects of intracoronary CD34+ cell transplantation on functional, structural, neurohormonal, and electrophysiologic parameters in patients with end-stage dilated cardiomyopathy.
详细描述
Patients were randomly allocated in a 1:1 ratio to receive intracoronary transplantation of autologous CD34+ stem cells (SC group) or no intracoronary infusion (control group). At the time of enrollment, and at yearly intervals thereafter, we performed detailed clinical evaluation, echocardiography, 6-minute walk test, and measured plasma levels of NT-proBNP. To better-define the potential role of inflammatory response, we also measured plasma inflammatory markers (tumor necrosis factor [TNF]-α and interleukin [IL]-6) at the time of CD34+ stem cell injection.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Normal coronary angiogram
- •Left ventricular ejection fraction < 40%
- •NYHA III or IV heart failure symptoms
- •Bone marrow reactivity (G-CSF test)
- •Presence of viable myocardium
排除标准
- •Hematologic malignancy
- •Multiorgan failure
研究组 & 干预措施
SC Group
SC therapy,'Bone Marrow Stimulation','CD34+ autologous stem cell transplantation':
In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect
干预措施: CD34+ autologous stem cell transplantation (Biological)
SC Group
SC therapy,'Bone Marrow Stimulation','CD34+ autologous stem cell transplantation':
In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect
干预措施: Bone Marrow Stimulation (Drug)
SC Group
SC therapy,'Bone Marrow Stimulation','CD34+ autologous stem cell transplantation':
In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect
干预措施: SC therapy (Biological)
结局指标
主要结局
Heart Failure Mortality
时间窗: 5 years
Changes in Left Ventricular Ejection Fraction
时间窗: 5 years
Left ventricular ejection fraction measured by echocardiography
次要结局
- Changes in Electrophysiologic Properties of Ventricular Myocardium(6 months)
- Changes in Plasma Inflammatory Markers(6 months)
- Changes in Exercise Capacity(5 years)
- Changes in Left Ventricular Function(5 years)
研究者
Bojan Vrtovec
prof. dr. Bojan vrtovec
University Medical Centre Ljubljana