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

Primary Purpose

Chronic Myocardial Ischemia

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Autologous MSC from bone marrow

Placebo comparator

About this trial

This is an interventional treatment trial for Chronic Myocardial Ischemia focused on measuring Mesenchymal stem cells, ischemic cardiomyopathy, NogaStar XP system catheter

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University hospital of Henri Mondor
University hospital of Grenoble
University hospital of Lille
University hospital of Nantes
University hospital of Pitié-Salpêtrière
Cardiology Department of Rangueil Hospital - Rangueil Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo comparator

Autologous MSC from bone marrow

Arm Description

injection of human albumin 4%

intramyocardial injection of 6.10e7 stem cells

Outcomes

Primary Outcome Measures

Change in VO2max

Change in VO2max (or peak VO2) before injection and at 3 months post injection.

Secondary Outcome Measures

Left ventricular viability

MRI

NYHA/CCS class

Change on class

Quality of life (Minnesota questionnaire)

Change on quality of life test score

VO2 max

Change in VO2max (or peak VO2) at 6 and 12 months post injection.

6'walking-test

Distance to walk test

Echocardiography

Volume of myocardium and measurement of ejection fraction

Myocardial perfusion imaging

Efficacy of the cell therapy on LVEF

BNP blood test

Change of the BNP blood test at 3, 6 and 12 months

Full Information

NCT ID

NCT02462330

First Posted

May 27, 2015

Last Updated

March 29, 2023

Sponsor

University Hospital, Toulouse

1. Study Identification

Unique Protocol Identification Number

NCT02462330

Brief Title

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

Acronym

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

February 19, 2016 (Actual)

Primary Completion Date

December 19, 2022 (Actual)

Study Completion Date

December 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Toulouse

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Myocardial Ischemia

Keywords

Mesenchymal stem cells, ischemic cardiomyopathy, NogaStar XP system catheter

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo comparator

Arm Type

Placebo Comparator

Arm Description

injection of human albumin 4%

Arm Title

Autologous MSC from bone marrow

Arm Type

Experimental

Arm Description

intramyocardial injection of 6.10e7 stem cells

Intervention Type

Drug

Intervention Name(s)

Autologous MSC from bone marrow

Other Intervention Name(s)

mesenchymal stem cells

Intervention Description

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

Intervention Name(s)

Placebo comparator

Other Intervention Name(s)

Human Albumin

Intervention Description

injections of human albumin

Primary Outcome Measure Information:

Title

Change in VO2max

Description

Change in VO2max (or peak VO2) before injection and at 3 months post injection.

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Left ventricular viability

Description

MRI

Time Frame

Before injection and at 3, 6 and 12 months

Title

NYHA/CCS class

Description

Change on class

Time Frame

Before injection and at 3, 6 and 12 months

Title

Quality of life (Minnesota questionnaire)

Description

Change on quality of life test score

Time Frame

Before injection and at 3, 6 and 12 months

Title

VO2 max

Description

Change in VO2max (or peak VO2) at 6 and 12 months post injection.

Time Frame

At 6 and 12 months

Title

6'walking-test

Description

Distance to walk test

Time Frame

Between 3 and 12 months

Title

Echocardiography

Description

Volume of myocardium and measurement of ejection fraction

Time Frame

Before injection and at 3, 6 and 12 months

Title

Myocardial perfusion imaging

Description

Efficacy of the cell therapy on LVEF

Time Frame

Before injection and at 3, 6 and 12 months

Title

BNP blood test

Description

Change of the BNP blood test at 3, 6 and 12 months

Time Frame

Before injection and at 3, 6 and 12 months

Other Pre-specified Outcome Measures:

Title

Adverse event related to cell administration

Time Frame

12 months

Title

Complication related to cell administration

Time Frame

12 months

Title

Control of the implantable cardioverter defibrillator

Time Frame

12 months

Title

Analysis of major cardiovascular events

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jerôme Roncalli, MD, PhD

Organizational Affiliation

Toulouse University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

University hospital of Henri Mondor

City

Créteil

ZIP/Postal Code

94010

Country

France

Facility Name

University hospital of Grenoble

City

Grenoble

ZIP/Postal Code

38043

Country

France

Facility Name

University hospital of Lille

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

University hospital of Nantes

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

University hospital of Pitié-Salpêtrière

City

Paris

ZIP/Postal Code

75651

Country

France

Facility Name

Cardiology Department of Rangueil Hospital - Rangueil Hospital

City

Toulouse

ZIP/Postal Code

31059

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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