Administration of Mesenchymal Stem Cells in Patients With Chronic Ischemic Cardiomyopathy (MESAMI2)

Condition(s) targeted: Chronic Myocardial Ischemia

Intervention: Autologous MSC from bone marrow (Drug); Placebo comparator (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: University Hospital, Toulouse

Official(s) and/or principal investigator(s):
Jerôme Roncalli, MD, PhD, Principal Investigator, Affiliation: Toulouse University Hospital

Overall contact:
Jerôme Roncalli, MD, PhD, Phone: 05 61 32 26 13, Ext: +33, Email: roncalli.j@chu-toulouse.fr

Stem cell therapy is an emerging treatment for cardiovascular disease but the best cell type and delivery method remain to be determined. Pre-clinical studies demonstrated improvement of cardiac function by Mesenchymal stem cells (MSC) therapy in particular by their paracrine and immunosuppressive properties. Investigators initiated the MESAMI program by the bicentric pilot phase and highlighted the safety and feasibility of intramyocardial injections of MSCs from bone marrow in patients with chronic ischemic cardiomyopathy and left ventricular dysfunction, guide by the NOGA-XP system. The MESAMI program continues with the phase 2, multicenter, double-blind, randomized, placebo-controlled trial. The aim of this phase 2 study is to demonstrate a functional improvement, measuring peak VO2, at 3 months between the cell therapy group and the placebo group.

Official title: Effect of Intramyocardial Mesenchymal Stem Cells Injection in Patients With Chronic Ischemic Cardiomyopathy and Left Ventricular Dysfunction Guide by NogaStar XP System Catheter.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Change in VO2max

Secondary outcome:

Left ventricular viability

NYHA/CCS class

Quality of life (Minnesota questionnaire)

VO2 max

6'walking-test

Echocardiography

myocardial perfusion imaging

Detailed description: Ischemic cardiomyopathies are a leading cause of death in both men and women. During the last decade, treatments for heart failure have evolved, but their purpose is to improve symptoms and prevent aggravation of the disease. Current research is focusing on the development of cell-based therapies using different sources of stem cells which can provide trophic and paracrine support or even replace dying cells with new ones. A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown promise for heart repair. These cells are known for their ability to secrete paracrine factors and their immunosuppressive properties. The MESAMI 2 study will evaluate the efficacy of MSCs injection directly into the heart to repair and restore heart function in people with chronic ischemic heart failure using NOGA-XP system. This phase 2 study is a prospective, multicenter, double-blind, randomized, placebo-controlled trial. A total of 90 patients will be randomized in 2 arms to receive intramyocardial injection of MSCs or placebo. Patients will be followed up for 13 months. Bone marrow will be collected and immediately transported to the French Blood Establishment for MSC isolation and expansion. Patients will receive intramyocardial injection of MSCs or placebo during a left heart catheterization.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patient who signed the informed consent,

- Chronic stable ischemic cardiomyopathy for at least one month with a NYHA Class II-IV

and/or - Angina pectoris CCS Class III or IV,

- Not a candidate for revascularization by coronary artery by-pass surgery or

angioplasty,

- Left ventricular function ≤45%,

- Presence of ischemia or myocardial viability on the myocardial perfusion imaging,

- VO2 max≤ 20 ml/min/kg,

- Optimal medical therapy,

- Optimal interventional therapy (Implantable Cardiovertor Defibrillator, effort

rehabilitation). Exclusion criteria:

- Pregnancy or breastfeeding,

- Acute coronary syndrome or myocardial infarction during the last 3 months,

- Revascularization (PCI or CABG), or cardiac resynchronization during the last 3

months,

- Further revascularization planned for the next 30 days,

- LVEF >45%,

- Left intraventricular Thrombus and / or ventricular aneurysm detected by

transthoracic echocardiography,

- Wall thickness in the target region <8 mm as determined by echocardiography,

- Critical Limb Ischemia stages 3 or 4,

- Inability to achieve a VO2 test,

- Not feasible peripheral arterial access for percutaneous procedure,

- Aortic stenosis (<1cm²) or aortic insufficiency (> 2 +),

- Patients with transplanted organ,

- Chronic renal failure with creatinemia ≥ 250 µmol/L,

- Severe hepatic dysfunction,

- Chronic atrial fibrillation,

- Decompensated heart failure,

- Uncontrolled Ventricular arrhythmias,

- Indication of cardiac resynchronization by multisite pacemaker or cardiac

resynchronization during the last 3 months,

- Obesity preventing bone marrow aspiration or manual compression of the puncture area

after bone marrow collection,

- Active uncontrolled infection

- Immuno-modulator treatment (ciclosporin, mycophenolate, mycophenolate mofetil,

azathioprine, tacrolimus, anthracyclines, neupogen, hydrea, etanercept interferons, prednisolone, methylprednisolone, colchicine),

- History of cancer in the last 5 years,

- Hemopathy, hematopoietic disease,

- Haemorrhagic syndrome,

- Chronic or progressive disease that may alter the prognosis within 3 months,

- Positive serologies for Human immunodeficiency virus (HIV1-2), HTLV-1 (human T-cell

lymphotrophic virus) and 2, HBV (hepatitis B virus) or HCV (hepatitis B virus).

- Allergic to xylocain.

Jerôme Roncalli, MD, PhD, Phone: 05 61 32 26 13, Ext: +33, Email: roncalli.j@chu-toulouse.fr

Cardiology Department of Rangueil Hospital - Rangueil Hospital, Toulouse 31059, France; Not yet recruiting
Jerôme Roncalli, MD, PhD, Phone: 05 61 32 26 13, Ext: +33, Email: roncalli.j@chu-toulouse.fr
Marine Lebrin, Phone: 05 61 32 37 24, Ext: +33, Email: lebrin.m@chu-toulouse.fr
Jerôme Roncalli, MD, PhD, Principal Investigator

Starting date: June 2015
Last updated: June 1, 2015