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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cytopeutics Sdn Bhd
Information provided by (Responsible Party):
Professor Dr Oteh Maskon, National University of Malaysia
ClinicalTrials.gov Identifier:
NCT01720888
First received: November 1, 2012
Last updated: April 15, 2015
Last verified: April 2015
  Purpose

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.


Condition Intervention Phase
Ischemic Dilated Cardiomyopathy
Other: BM-MSCs
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by National University of Malaysia:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in functional status [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Resolution of scar tissue volume/area on cardiac MRI [ Time Frame: 6 months, 12 months. ] [ Designated as safety issue: No ]
  • Change in serum N Terminal-pro B type natriuretic peptide(NT-proBNP)level [ Time Frame: 1 month, 6 months, 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • No peri-procedural complications [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]
  • Significant improvement in overall left ventricular function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Resolution of scar tissue [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
  • Reduction of major adverse cardiac events [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
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)
Arms Assigned Interventions
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
Other: BM-MSCs
Intracoronary implantation of bone marrow-derived mesencymal stem cells
Other Name: Bone marrow-derived mesenchymal stem cells implantation

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.

  Eligibility

Ages Eligible for Study:   35 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01720888

Locations
Malaysia
UKM Medical Centre
Cheras, Kuala Lumpur, Malaysia, 56000
Sponsors and Collaborators
National University of Malaysia
Cytopeutics Sdn Bhd
Investigators
Principal Investigator: Oteh Maskon, MB Bch Universiti Kebangsaan Malaysia Medical Centre
  More Information

No publications provided

Responsible Party: Professor Dr Oteh Maskon, Professor, National University of Malaysia
ClinicalTrials.gov Identifier: NCT01720888     History of Changes
Other Study ID Numbers: ERGS/1/2011/SKK/UKM/02/72
Study First Received: November 1, 2012
Last Updated: April 15, 2015
Health Authority: Malaysia: Ministry of Health
Malaysia: Institutional Review Board

Keywords provided by National University of Malaysia:
Autologous
Bone Marrow
Mesenchymal Stem Cells
Ischemic Dilated Cardiomyopathy

Additional relevant MeSH terms:
Cardiomyopathies
Cardiomyopathy, Dilated
Ischemia
Cardiomegaly
Cardiovascular Diseases
Heart Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 27, 2015