Intracoronary Autologous Mesenchymal Stem Cells Implantation in Patients With Ischemic Dilated Cardiomyopathy

Ischemic Dilated Cardiomyopathy Clinical Trial

Official title:

A Controlled Open Label Phase II Study Assessing the Efficacy of Intracoronary Autologous Mesenchymal Stem Cells in Patients With Ischemic Dilated Cardiomyopathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01720888
• Other study ID #: ERGS/1/2011/SKK/UKM/02/72
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 1, 2012
• Last updated: April 15, 2015
• Start date: July 2012
• Est. completion date: December 2015

Study information

• Verified date: April 2015
• Source: National University of Malaysia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Malaysia: Ministry of HealthMalaysia: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Ischemia
• Ischemic Dilated Cardiomyopathy

Intervention

Other:
• BM-MSCs
Intracoronary implantation of bone marrow-derived mesencymal stem cells

Locations

Country	Name	City	State
Malaysia	UKM Medical Centre	Cheras	Kuala Lumpur

Sponsors (2)

Lead Sponsor	Collaborator
National University of Malaysia	Cytopeutics Sdn Bhd

Country where clinical trial is conducted

Malaysia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	No peri-procedural complications		1 month, 3 months, 6 months, 9 months, 12 months	Yes
Other	Significant improvement in overall left ventricular function		12 months	No
Other	Resolution of scar tissue		6 months, 12 months	No
Other	Reduction of major adverse cardiac events		1 month, 3 months, 6 months, 9 months, 12 months	Yes
Primary	Change in LV ejection fraction as measured by echocardiogram and cardiac MRI after implantation		1 month, 3 months, 6 months, 9 months, 12 months	No
Secondary	Changes in functional status		12 months	No
Secondary	Improvement in other LV parameters as assessed by echocardiogram and cardiovascular magnetic resonance(CMR).		1 months, 3 months, 6 months, 9 months, 12 months	Yes
Secondary	Resolution of scar tissue volume/area on cardiac MRI		6 months, 12 months.	No
Secondary	Change in serum N Terminal-pro B type natriuretic peptide(NT-proBNP)level		1 month, 6 months, 12 months	No
Secondary	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	Yes