Stem Cell in Acute Myocardial Infarction

Study Overview
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Brief Summary
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The study will perform UC-MSCs transplantation in 2 groups and 1 control group with standard treatment. Each group consists of 5 subjects. In the first group UC-MSCs will be transplanted via intravenous (IV) route and the second group via intracoronary (IC) route. The IV group will receive 2 million cells/kg for each subject and the dosage of IC group is 50 million cells for each subject. All groups will be observed until 1 year.

Official Title
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Allogeneic Umbilical Cord Mesenchymal Stem Cell Therapy for Acute Myocardial Infarction

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Biological: Mesenchymal Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: STEMI patients within 5 days after symptom onset of a first ST-segment elevation myocardial infarction Have undergone successful percutaneous coronary intervention (PCI) with drug eluting stent implantation of the infarct-related artery and demonstrated hypokinesia or akinesia that involved more than two thirds of the LV anteroseptal, lateral, or inferior wall with LV ejection fraction of < 45% by echocardiography. Ability to understand and provide signed informed consent, or have a designated legal guardian or spouse legally able and willing to make such decisions on the subject's behalf, Willingness to attend all scheduled safety follow-up visits Subjects need to have a specific criteria of having a single vessel disease (ostial or proximal LAD vessels) that caused extensive anterior infarction (EF <45). Exclusion Criteria: Hemodynamic instability as demonstrated by any of the following, Requirement of intra-aortic balloon pump of left ventricular assist device, Need for inotropic support (e.g. dopamine and/or dobutamine) for more than 36 hours for the maintenance of mean arterial blood pressure ≥ 60 mmHg, Previous or current concomitant serious illnesses, such as cancer, hematological disorders (Hb < 10 g/dL, WBC < 4 or > 11x109/L, or platelets < 100x109/L), kidney failure (creatinine level > 2.5 mg/dL, or creatinine clearance < 30 cc/min), serious infection or any other co-morbidities that could impact patient's short-term survival, psychiatric illness, history of drug of alcohol abuse, Prosthetic valves, Hypertrophic or restrictive cardiomyopathy, Women of child-bearing potential, Inability to comply with the protocol, Currently using implantable electronic defibrillator or pacemaker

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Group<br>Dosage of intravenous route is 2 million MSCs/kg for each subject. | Biological: Mesenchymal Stem Cells<br>* The UC-MSCs from a donor will be cultured in a clinical grade laboratory with xeno-free medium. Maximum passage of expanded-UC MSCs was VI and doubling population is less than 30. To assure the quality of our expanded-UC MSCs at ProSTEM the following tests are done: cell adherence, cell surface marker, in vitro differentiation, cell viability, sterility, Mycoplasma, endotoxin, and karyotyping.<br>|
| Experimental: Intracoronary Group<br>Dosage of intracoronary route is ±50 million MSCs for each subject. | Biological: Mesenchymal Stem Cells<br>* The UC-MSCs from a donor will be cultured in a clinical grade laboratory with xeno-free medium. Maximum passage of expanded-UC MSCs was VI and doubling population is less than 30. To assure the quality of our expanded-UC MSCs at ProSTEM the following tests are done: cell adherence, cell surface marker, in vitro differentiation, cell viability, sterility, Mycoplasma, endotoxin, and karyotyping.<br>|
| No Intervention: Control Group<br>Standard treatment of acute myocardia infarction | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiac events (MACE) endpoints of mortality | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 2 weeks after stem cell | 
| Major adverse cardiac events (MACE) endpoints of mortality | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 3 months after stem cell | 
| Major adverse cardiac events (MACE) endpoints of mortality | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 6 months after stem cell | 
| Major adverse cardiac events (MACE) endpoints of mortality | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 12 months after stem cell | 
| Re-infarction | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 2 weeks after stem cell | 
| Re-infarction | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 3 months after stem cell | 
| Re-infarction | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 6 months after stem cell | 
| Re-infarction | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 12 months after stem cell | 
| Target vessel revascularization (TVR) | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 2 weeks after stem cell | 
| Target vessel revascularization (TVR) | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 3 months after stem cell | 
| Target vessel revascularization (TVR) | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 6 months after stem cell | 
| Target vessel revascularization (TVR) | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 12 months after stem cell | 
| Heart failure hospitalization | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 2 weeks after stem cell | 
| Heart failure hospitalization | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 3 months after stem cell | 
| Heart failure hospitalization | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 6 months after stem cell | 
| Heart failure hospitalization | To assess the safety of using allogeneic UC-MSCs therapy for acute myocardial infarction. | 12 months after stem cell | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac MRI | a test to see improvement in LVEF(%), improvement in regional function, improvement in perfusion, reduction of infarct size. | 6 months after stem cell | 
| Cardiac MRI | a test to see improvement in LVEF (%), improvement in regional function, improvement in perfusion, reduction of infarct size. | 12 months after stem cell | 
| Echocardiography | Left ventricular volumes will be determined at end-diastole and end-systole by quantitative biplane assessment. Endocardial borders will be manually traced from apical four-chamber and two-chamber views. Left ventricular volumes will be used to calculate ejection fraction using the biplane modified Simpson's summation-of-disks method recommended by the American Society of Echocardiography. | 6 months after stem cell | 
| Echocardiography | Left ventricular volumes will be determined at end-diastole and end-systole by quantitative biplane assessment. Endocardial borders will be manually traced from apical four-chamber and two-chamber views. Left ventricular volumes will be used to calculate ejection fraction using the biplane modified Simpson's summation-of-disks method recommended by the American Society of Echocardiography. | 12 months after stem cell | 
| Electrocardiography (ECG) | to detects cardiac (heart) abnormalities by measuring the electrical activity generated by the heart as it contracts | 3 months after stem cell | 
| Electrocardiography (ECG) | to detects cardiac (heart) abnormalities by measuring the electrical activity generated by the heart as it contracts | 6 months after stem cell | 
| Electrocardiography (ECG) | to detects cardiac (heart) abnormalities by measuring the electrical activity generated by the heart as it contracts | 12 months after stem cell | 
| Wellness Parameter | hs-CRP, antioxidant, IL-6, IL-10, PA1, Fibrinogen | 6 months after stem cell | 
| Laboratory Assessment | Haematology, Serum Chemistry, Cardiac Biomarker | 12 months after stem cell | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic Mesenchymal Stem Cells, Umbilical Cord Mesenchymal Stem Cells, Intravenous Mesenchymal Stem Cells, Intracoronary Mesenechymal Stem Cells