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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Myocardial Ischemia
• Intervention / Treatment: Drug: Placebo comparator; Drug: Autologous MSC from bone marrow

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94010
    • University hospital of Henri Mondor
  • Grenoble, France, 38043
    • University Hospital of Grenoble
  • Lille, France, 59037
    • University Hospital of Lille
  • Nantes, France, 44093
    • University Hospital of Nantes
  • Paris, France, 75651
    • University hospital of Pitié-Salpêtrière
  • Toulouse, France, 31059
    • Cardiology Department of Rangueil Hospital - Rangueil Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo comparator; injection of human albumin 4%	Drug: Placebo comparator; injections of human albumin; Other Names: Human Albumin
Experimental: Autologous MSC from bone marrow; intramyocardial injection of 6.10e7 stem cells	Drug: 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.; Other Names: mesenchymal stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VO2max	Change in VO2max (or peak VO2) before injection and at 3 months post injection.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular viability	MRI	Before injection and at 3, 6 and 12 months
NYHA/CCS class	Change on class	Before injection and at 3, 6 and 12 months
Quality of life (Minnesota questionnaire)	Change on quality of life test score	Before injection and at 3, 6 and 12 months
VO2 max	Change in VO2max (or peak VO2) at 6 and 12 months post injection.	At 6 and 12 months
6'walking-test	Distance to walk test	Between 3 and 12 months
Echocardiography	Volume of myocardium and measurement of ejection fraction	Before injection and at 3, 6 and 12 months
Myocardial perfusion imaging	Efficacy of the cell therapy on LVEF	Before injection and at 3, 6 and 12 months
BNP blood test	Change of the BNP blood test at 3, 6 and 12 months	Before injection and at 3, 6 and 12 months

Other Outcome Measures

Outcome Measure	Time Frame
Adverse event related to cell administration	12 months
Complication related to cell administration	12 months
Control of the implantable cardioverter defibrillator	12 months
Analysis of major cardiovascular events	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Jerôme Roncalli, MD, PhD, Toulouse University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2016
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): December 19, 2022

Study Registration Dates

• First Submitted: May 27, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Mesenchymal stem cells; ischemic cardiomyopathy; NogaStar XP system catheter
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Ischemia; Ischemia; Cardiomyopathies
• Other Study ID Numbers: 10 142 01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO