Bone Marrow-derived Mesenchymal Stem Cells (MSC) Administration in Weaning From Left Ventricular Assist Device

Study Overview
=================
Brief Summary
-----------------
Left Ventricular Assist Devices are commonly used to assist failing hearts as a bridge to transplantation or for long-term support. The purpose of the MESenchymal stem cell therapy and Left Ventricular Assist Device program is to improve heart function with stem cell therapy and attempt to wean patients from HeartMate Left Ventricular Assist Device.

Detailed Description
-----------------
Currently Left Ventricular Assist Device-only patients are being implanted and followed. Feasibility of autologous mesenchymal stem cell grafting in patients receiving heart mate will be assessed in a 4 patient pilot trial. Mesenchymal stem cell are delivered during Left Ventricular Assist Device surgery by intramyocardial infusions. Recovery of contractile function of the heart is assessed during attempts to wean patients from Left Ventricular Assist Device

Official Title
-----------------
Pilot Study of Investigation of Bone Marrow-derived Mesenchymal Stem Cells (MSC) Administration in Weaning From Left Ventricular Assist Device

Conditions
-----------------
Chronic Myocardial Ischemia

Intervention / Treatment
-----------------
* Drug: Autologous mesenchymal stem cells


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Postmenopausal female or female who may become pregnant but is using adequate contraceptive precautions with negative pregnancy test, Severe Left Ventricular dysfunction with Ejection Fraction < 30% with ischemic cardiomyopathy, New York Heart Association Class III or IV, No revascularization options available, Listed or not for cardiac transplantation, Clinical indication and accepted candidate for Left Ventricular Assistance Device implantation as a destination therapy or as a bridge to transplantation, Optimal medical therapy. EXCLUSION CRITERIA: Cardiothoracic surgery within 30 days prior to study entry, Myocardial infarction within 3 months prior to study entry, Prior cardiac transplantation, Left Ventricular reduction surgery or cardiomyoplasty, Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism), Left ventricular aneurysm or wall thickness preventing cell injections, Anticipated requirement for biventricular mechanical support, Stroke within 30 days prior to study entry, Received investigational intervention within 30 days of study entry, Pregnant or breastfeeding at time of study entry, Human Imune deficiency Virus, Human T-cell Lymphotrophic Virus, Hepatitis B Virus and Hepatitis C Virus positive within 30 days prior to study entry, Active systemic infection within 48 hours prior to study entry, History of cancer in the last 5 years, Patient participant to other research, Patient under treatment that may exert an inhibitory or stimulatory effect on the growth and multiplication of cells, or with immunosuppressive properties.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: autologous mesenchymal stem cells<br>After bone-marrow aspiration by an authorized person, Mesenchymal Stem Cells were isolated and cultured during 17 days by the French Blood Establishment. Then, patients receive intramyocardial injections of Mesenchymal Stem Cells during Left Ventricular Assist Device surgery | Drug: Autologous mesenchymal stem cells<br>* After bone-marrow aspiration by an authorized person, mesenchymal stem cells were isolated and cultured during 17 days by the French Blood Establishment. Then, patients receive intramyocardial injections of mesenchymal stem cells during device surgery.<br>* Other names: MSC;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the full procedure | ability to perform bone marrow aspiration, cell culture and intramyocardial injections during left Ventricular Assist Device surgery Realization of a full injection procedure | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ejection Fraction | Global and regional contractile function during echocardiography | 12 months | 
| Maximal Oxygen consumption | Maximum rate of oxygen consumption as measured during incremental exercise, modification of the body mass (muscular lean mass, muscular strength), duration of the test and load, | 12 months | 
| Walking distance in 6 minutes | measure of walk distance during six minutes | 12 months | 
| weaning procedure | progressive reduction of the pump speed | 12 months | 
| Quality of life | assessment of quality of life by Minnesota Living with Heart Failure Questionnaire | 12 months | 
| Measure of heart pressures | measure of heart pressures and cardiac output | 12 months | 
| Brain natriuretic peptide | assessment of variation of brain natriuretic peptide | 12 months | 
| Troponin | assessment of variation of troponin | 12 months | 
| Major bleeding |  | 1 month | 
| Systemic embolism |  | 1 month | 
| Deaths |  | 1 month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Left Ventricular Assist Device, stem cell therapy, ischemic heart failure