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

Brief Title

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

Official Title

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

Brief 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.
    

Detailed 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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Change in LV ejection fraction as measured by echocardiogram and cardiac MRI after implantation

Secondary Outcome

 Changes in functional status

Condition

Ischemic Dilated Cardiomyopathy

Intervention

BM-MSCs

Study Arms / Comparison Groups

 Maximal medical therapy

Description:  Maximal medical therapy which comprises of optimal pharmacological therapy

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Other

Estimated Enrollment

80

Start Date

July 2012

Completion Date

December 2015

Primary Completion Date

December 2015

Eligibility Criteria

        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.
      

Gender

All

Ages

35 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Oteh Maskon, MB Bch, , 

Location Countries

Malaysia

Location Countries

Malaysia

NCT ID

NCT01720888

Organization ID

ERGS/1/2011/SKK/UKM/02/72

Responsible Party

Principal Investigator

Study Sponsor

National University of Malaysia

Collaborators

 Cytopeutics Sdn. Bhd.

Study Sponsor

Oteh Maskon, MB Bch, Principal Investigator, Universiti Kebangsaan Malaysia Medical Centre

Verification Date

April 2015