Intracoronary Autologous Mesenchymal Stem Cells Implantation in Patients With Ischemic Dilated Cardiomyopathy
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Controlled Open Label Phase II Study Assessing the Efficacy of Intracoronary Autologous Mesenchymal Stem Cells in Patients With Ischemic Dilated Cardiomyopathy|
- Change in LV ejection fraction as measured by echocardiogram and cardiac MRI after implantation [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ]
- Changes in functional status [ Time Frame: 12 months ]
- Improvement in other LV parameters as assessed by echocardiogram and cardiovascular magnetic resonance(CMR). [ Time Frame: 1 months, 3 months, 6 months, 9 months, 12 months ]
- Resolution of scar tissue volume/area on cardiac MRI [ Time Frame: 6 months, 12 months. ]
- Change in serum N Terminal-pro B type natriuretic peptide(NT-proBNP)level [ Time Frame: 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). [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ]
- No peri-procedural complications [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ]
- Significant improvement in overall left ventricular function [ Time Frame: 12 months ]
- Resolution of scar tissue [ Time Frame: 6 months, 12 months ]
- Reduction of major adverse cardiac events [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ]
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
No Intervention: Maximal medical therapy
Maximal medical therapy which comprises of optimal pharmacological therapy
Experimental: Maximal medical therapy and BM-MSCs
Autologous Bone marrrow-derived mesenchymal stem cells implantation
Intracoronary implantation of bone marrow-derived mesencymal stem cells
Other Name: Bone marrow-derived mesenchymal stem cells implantation
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01720888
|UKM Medical Centre|
|Cheras, Kuala Lumpur, Malaysia, 56000|
|Principal Investigator:||Oteh Maskon, MB Bch||Universiti Kebangsaan Malaysia Medical Centre|