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

NCT ID: NCT02462330

Last Updated: 2023-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-19
• Study Completion Date: 2022-12-19

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.

Conditions

Chronic Myocardial Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo comparator

injection of human albumin 4%

Group Type: PLACEBO_COMPARATOR

Placebo comparator

Intervention Type: DRUG

injections of human albumin

Autologous MSC from bone marrow

intramyocardial injection of 6.10e7 stem cells

Group Type: EXPERIMENTAL

Autologous MSC from bone marrow

Intervention Type: DRUG

After bone-marrow aspiration by an authorized person, MSCs were isolated and cultured during 17±2 days by the French Blood Establishment. Then, patients receive intramyocardial injections of MSCs using the electromechanical NOGA-XP system.

Interventions

Autologous MSC from bone marrow

After bone-marrow aspiration by an authorized person, MSCs were isolated and cultured during 17±2 days by the French Blood Establishment. Then, patients receive intramyocardial injections of MSCs using the electromechanical NOGA-XP system.

Intervention Type: DRUG

Placebo comparator

injections of human albumin

Intervention Type: DRUG

Other Intervention Names

mesenchymal stem cells; Human Albumin

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jerôme Roncalli, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

University hospital of Henri Mondor

Créteil, , France

University hospital of Grenoble

Grenoble, , France

University hospital of Lille

Lille, , France

University hospital of Nantes

Nantes, , France

University hospital of Pitié-Salpêtrière

Paris, , France

Cardiology Department of Rangueil Hospital - Rangueil Hospital

Toulouse, , France

Countries

France

Other Identifiers

10 142 01

Identifier Type: -

Identifier Source: org_study_id