Clinical trial NCT02462330: Administration of Mesenchymal Stem Cells in Patients With Chronic Ischemic Cardiomyopathy (MESAMI2)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myocardial Ischemia
Keywords: Mesenchymal stem cells
ischemic cardiomyopathy
NogaStar XP system catheter
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2015-06-04
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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.

Primary outcomes:
measure: Change in VO2max
timeFrame: 3 months
Secondary outcomes:
measure: Left ventricular viability
timeFrame: Before injection and at 3, 6 and 12 months
measure: NYHA/CCS class
timeFrame: Before injection and at 3, 6 and 12 months
measure: Quality of life (Minnesota questionnaire)
timeFrame: Before injection and at 3, 6 and 12 months
measure: VO2 max
timeFrame: At 6 and 12 months
measure: 6'walking-test
timeFrame: Between 3 and 12 months
measure: Echocardiography
timeFrame: Before injection and at 3, 6 and 12 months
measure: Myocardial perfusion imaging
timeFrame: Before injection and at 3, 6 and 12 months
measure: BNP blood test
timeFrame: Before injection and at 3, 6 and 12 months
Other outcomes:
measure: Adverse event related to cell administration
timeFrame: 12 months
measure: Complication related to cell administration
timeFrame: 12 months
measure: Control of the implantable cardioverter defibrillator
timeFrame: 12 months
measure: Analysis of major cardiovascular events
timeFrame: 12 months
Locations:
city: Créteil
country: France
facility: University hospital of Henri Mondor
city: Grenoble
country: France
facility: University hospital of Grenoble
city: Lille
country: France
facility: University hospital of Lille
city: Nantes
country: France
facility: University hospital of Nantes
city: Paris
country: France
facility: University hospital of Pitié-Salpêtrière
city: Toulouse
country: France
facility: Cardiology Department of Rangueil Hospital - Rangueil Hospital
Study officials:
affiliation: University Hospital, Toulouse
name: Jerôme Roncalli, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: