A Controlled Open Label Phase II Study Assessing the Efficacy of Intracoronary Autologous Mesenchymal Stem Cells in Patients With Ischemic Dilated Cardiomyopathy
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Change in LV ejection fraction as measured by echocardiogram and cardiac MRI after implantation
研究概览
简要总结
Despite the recent advances in medical and surgical treatment, heart failure resulting from ischemic cardiomyopathy (ICM) remains the leading cause of cardiovascular mortality. Ischemic dilated cardiomyopathy(ICM) is defined as abnormally enlarged left ventricular (LV) cavity with documented poor LV function as a result of severe coronary artery disease (CAD). LV remodelling which is inevitable after an infarct has been postulated to contribute largely to the poor outcome of patients with ICM, therefore prevention of LV remodelling is the goal for the treatment in patients with severe CAD. Cell therapy represents a novel therapeutic strategy for treating cardiac diseases including severe CAD and heart failure. A type of stem cells known as mesenchymal stem cells(MSCs)can be isolated from bone marrow.This study aims to test the differentiation potential and therapeutic capacity of MSC from severe CAD patients after intracoronary implantation in an ischemic myocardial environment in Malaysian population.
详细描述
Ischemic dilated cardiomyopathy(ICM) is defined as abnormally enlarged left ventricular (LV) cavity with documented poor LV function as a result of severe coronary artery disease (CAD). LV remodelling which is inevitable after an infarct has been postulated to contribute largely to the poor outcome of patients with ICM, therefore prevention of LV remodelling is the goal for the treatment in patients with severe CAD. Cell therapy represents a novel therapeutic strategy for treating cardiac diseases including severe CAD and heart failure. A type of stem cells known as mesenchymal stem cells(MSCs)can be isolated from bone marrow. Experimental and clinical studies to date have shown that mesenchymal stem cells represent the most suitable cell type for regeneration therapy after myocardial infarction (MI). After injection into ischemic myocardium, bone marrow-derived MSC (BM-MSC) from various animal species can differentiate into multiple cell lineages, including endothelial cells and cardiomyocytes, thereby improving LV function.
In Malaysia we have previously demonstrated our capability in isolating and extracting MSC from a small volume of bone marrow aspirates.The isolation, expansion and feasibility of storage, transport and differentiation of human MSC for clinical application has been performed locally. The researchers used autologous BM-MSC, ex vivo expanded, on three patients with end-stage ischemic dilated cardiomyopathy who were on the heart transplant waiting list and each patient was injected with MSCs directly into the myocardium during open heart surgery. After twelve months, all patients remained alive and well with significant improvement in cardiac function, quality of life and other parameters including reduction of myocardial scar volume as seen from cardiac scans.
The same group of researchers further carried out a study on ten patients with severe dilated cardiomyopathy and refractory cardiac function despite maximum medical therapy to receive autologous BM-MSC implantation via intramyocardial or intracoronary route. All patients remained alive at 1 year while recorded significant improvements in LV ejection fraction and other LV parameters from baseline to 6 and 12 months. Reduction in scar was also noted in six of the patients by 12 months.
Following these results, this study aims to test the differentiation potential and therapeutic capacity of MSC from severe CAD patients after intracoronary implantation in an ischemic myocardial environment in Malaysian population.
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
- None
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •aged between 35 to 75 years
- •diagnosed to have ICM confirmed by previous coronary angiogram showing significant coronary artery disease >70% or history of previous myocardial infarction.
- •myocardial infarction event occured 6 months or longer from time of screening.
- •LV ejection fraction of ≤40% by echocardiogram or cardiac MRI.
排除标准
- •Likelihood of heart failure from other causes such as idiopathic, infective or metabolic cardiomyopathy,valvular heart disease and pericardial disease.
- •patients who had undergone a coronary artery bypass graft(CABG) procedure.
- •patients who do not have any visible/significant myocardial scar.
- •patients with any cardiovascular metallic implantation.
- •any contraindication to bone marrow aspiration
- •any contraindication to coronary contrast angiography and angioplasty.
- •any acute or chronic communicable diseases including Hepatitis B, Hepatitis C and HIV.
- •any past history of neoplasia and primary haematological disease.
- •any current, past or paroxysmal cardiac arrhythmias.
- •renal impairment indicated by creatinine clearance of less than 30 ml/min.
- •liver impairment indicated by serum alanine transferase level at 4 times greater than normal value.
结局指标
主要结局
Change in LV ejection fraction as measured by echocardiogram and cardiac MRI after implantation
时间窗: 1 month, 3 months, 6 months, 9 months, 12 months
次要结局
- Changes in functional status(12 months)
- Improvement in other LV parameters as assessed by echocardiogram and cardiovascular magnetic resonance(CMR).(1 months, 3 months, 6 months, 9 months, 12 months)
- Resolution of scar tissue volume/area on cardiac MRI(6 months, 12 months.)
- Change in serum N Terminal-pro B type natriuretic peptide(NT-proBNP)level(1 month, 6 months, 12 months)
- Freedom from major adverse cardiac events as defined by myocardial infarction, hospitalization for angina, myocardial infarction or heart failure, or death (all cause of mortality).(1 month, 3 months, 6 months, 9 months, 12 months)
研究者
Professor Dr Oteh Maskon
Professor
National University of Malaysia