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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by National University of Malaysia.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Cytopeutics Pte. Ltd.
Information provided by:
National University of Malaysia
ClinicalTrials.gov Identifier:
NCT01720888
First received: November 1, 2012
Last updated: NA
Last verified: March 2012
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Ischemic Dilated Cardiomyopathy
Other: Bone Marrow derived Mesenchymal Stem cells Implantation
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 after implantation [ Time Frame: 1 month, 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]
  • Change in LV ejection fraction as measured by cardiac MRI after implantation. [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in functional status [ Designated as safety issue: Yes ]
  • Improvement in other LV parameters as assessed by echocardiogram and cardiovascular magnetic resonance(CMR). [ Designated as safety issue: Yes ]
  • Resolution of scar tissue volume/area on cardiac MRI [ Time Frame: 6 months, 12 months. ] [ Designated as safety issue: Yes ]
  • Change in serum 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). [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • No peri-procedural complications [ Designated as safety issue: Yes ]
  • Significant improvement in overall left ventricular function [ Designated as safety issue: No ]
  • Resolution of scar tissue
  • Reduction of major adverse cardiac events [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: July 2012
Arms Assigned Interventions
No Intervention: Control
Maximal medical therapy which comprises of optimal pharmacologocial therapy(including diuretics, ACE inhibitors or ARB, and/or beta blockers) and percutaneous coronary angioplasty with or without stent as indicated and according to clinical practice guidelines.
Experimental: Bone Marrow derived Mesenchymal Stem cells Implantation
Intracoronary implantation of BM-MSC at a cell dosage of 2 million cells per body weight in kilograms. Subjects will also received maximal medical therapy.
Other: Bone Marrow derived Mesenchymal Stem cells Implantation

  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 in farction.
  • 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 Recruiting
Cheras, Kuala Lumpur, Malaysia, 56000
Contact: Oteh Maskon, MB Bch    6019-3217351    auajwad@yahooo.com   
Principal Investigator: Oteh Maskon, MB Bch         
Sub-Investigator: Hamat Hamdi Che Hassan, MB Bch         
Sub-Investigator: Osama Ali Ibrahim, MD         
Sub-Investigator: Choor Chee Ken, MD         
Sponsors and Collaborators
National University of Malaysia
Cytopeutics Pte. Ltd.
Investigators
Principal Investigator: Oteh Maskon, MB Bch Universiti Kebangsaan Malaysia Medical Centre
  More Information

No publications provided

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: November 1, 2012
Health Authority: Malaysia: Ministry of Health

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

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

ClinicalTrials.gov processed this record on October 02, 2014