Mesenchymal Stem Cells and Myocardial Ischemia (MESAMI)

Administration of Mesenchymal Stem Cells in Patients With Chronic Ischemic Cardiomyopathy

Ischemic cardiomyopathies are a leading cause of death in both men and women. When a person has a heart attack, blood is unable to reach a certain area of the heart, and if the blood supply is not re-established quickly, that area of the heart can suffer permanent damage. While recovery from a heart attack can be managed through medications and lifestyle changes, these treatments can not reverse the all damage to the heart. Current research is focusing on the development of cell-based therapies using stem cells to repair organs that have been irreversibly damaged by disease. A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown promise for heart repair. This study will evaluate the safety of injecting MSCs directly into the heart to repair and restore heart function in people who have had a heart attack and who have chronic myocardial ischemia with heart failure.

Study Overview

• Status: Completed
• Conditions: Left Ventricular Dysfunction; Chronic Myocardial Ischemia
• Intervention / Treatment: Genetic: Mesenchymal stem cells

Detailed Description

Mesenchymal stem cells from the bone marrow can differentiate into endothelial cells and participate in the development of new blood vessels in ischemic tissue. The aim of the study is in a phase I safety study to evaluate the clinical effect of autologous mesenchymal stem cell therapy in patients with severe chronic myocardial ischemia.10 patients with reversible ischemia on a SPECT will be treated with direct intramyocardial injections of autologous isolated and expanded mesenchymal stem cells.Clinical and objective evaluations will be performed at baseline and during 24 months follow-up.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • University Hospital (Rangueil)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 75
2. Male or female
3. NYHA (Heart failure) Class II-IV or Angina pectoris CCS Class III or IV or symptoms consistent with)
4. Chronic coronary artery disease with left ventricular function below 35%
5. Stable medical therapy for at least one month
6. Reversible perfusion defects by SPECT
7. Not a candidate for coronary artery by-pass surgery due to poor targets or small vessels and not a candidate for percutaneous intervention due to small vessels or unreachable coronary lesions due to complicated anatomy
8. Implantable Cardiovertor Defibrillator

Exclusion Criteria:

1. Acute coronary syndrome, revascularization (PCI or CABG), or cardiac resynchronization during the last 3 months
2. Sustained ventricular
3. Further revascularization planned for the next 30 days.
4. Chronic atrial fibrillation.
5. A wall thickness in the target region <8 mm as determined by 2D echocardiography (the target region is defined at the time of NOGA® mapping).
6. An LV thrombus.
7. Severe peripheral vascular disease precluding femoral artery access as determined at time of original catheterization.
8. Aortic stenosis as determined as valve area less than 1 cm2 that prohibits catheter access to the LV.
9. Human immunodeficiency virus (HIV1-2), HTLV-1 and 2.
10. An active uncontrolled infection.
11. A prosthetic aortic valve.
12. A current or prior history within the last 3 years of neoplasm (excluding basal cell) and/or any active neoplasm within the last 24 months.
13. Pregnancy or breastfeeding.
14. Active participation in other research therapy for cardiovascular repair/regeneration.
15. Any medical condition that would affect the investigator's ability to evaluate the subject's condition or could compromise the subject's safety.
16. Any condition that, in the judgment of the investigator, would prohibit the subject from participating in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm	Genetic: Mesenchymal stem cells; 60x106 MSCs Trans-endocardial intramyocardial injections (n=14-16)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate safety and feasibility of transendocardial injection using the NogaStar XP Mapping Catheter with the MyostarTM Left Ventricular Injection Catheter of autologous MSC in subjects with chronic myocardial ischemia and left ventricular dysfunction	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in SF-36, VO2max, 6 min walk test, and the NYHA, CCS Classifications Effect related to cardiac function	30 days to 2 years

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: Ministry of Health, France; Nantes University Hospital; French Blood Establishment
• Investigators: Principal Investigator: jerome RONCALLI, MD, PhD, University Hospital of Toulouse

Publications and helpful links

General Publications

• Guijarro D, Lebrin M, Lairez O, Bourin P, Piriou N, Pozzo J, Lande G, Berry M, Le Tourneau T, Cussac D, Sensebe L, Gross F, Lamirault G, Huynh A, Manrique A, Ruidavet JB, Elbaz M, Trochu JN, Parini A, Kramer S, Galinier M, Lemarchand P, Roncalli J. Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial. Int J Cardiol. 2016 Apr 15;209:258-65. doi: 10.1016/j.ijcard.2016.02.016. Epub 2016 Feb 2.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: February 10, 2010
• First Submitted That Met QC Criteria: February 25, 2010
• First Posted (Estimate): February 26, 2010

Study Record Updates

• Last Update Posted (Estimate): September 19, 2014
• Last Update Submitted That Met QC Criteria: September 18, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Ischemia; Ventricular Dysfunction; Ventricular Dysfunction, Left
• Other Study ID Numbers: 0505008