The Transendocardial Autologous Cells (hMSC) or (hMSC) and (hCSC) in Ischemic Heart Failure Trial.

Study Overview
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Brief Summary
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Before initiating the full randomized study, a Pilot Safety Phase will be performed. In this phase the composition of cells administered via the Biosense Webster MyoStar NOGA Injection Catheter System will be tested. The randomized portion of the study will be conducted after a full review of the safety data from the pilot Phase by the Data safety monitoring board. Following the Pilot Phase of five (5) Fifty (50) patients scheduled to undergo cardiac catheterization and meeting all inclusion/exclusion criteria will be evaluated at baseline. Patients will be randomized in a 2:2:1 ratio to one of three Treatment Strategies.

Detailed Description
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A Phase I/II, Randomized, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Mesenchymal or the combination of MSC and Cardiac Stem Cells) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction. A total of 55 subjects participating, with 5 in the pilot phase and 50 in the randomized phase. Patients with chronic ischemic left ventricular dysfunction and heart failure secondary to MI scheduled to undergo cardiac catheterization.

Official Title
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A Phase I/II, Randomized, Placebo-Controlled Study of the Safety and Efficacy of Transendocardial Injection of Autologous Human Cells (Mesenchymal or the Combination of MSC and Cardiac Stem Cells) in Patients With Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction.

Conditions
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Chronic Ischemic Left Ventricular Dysfunction, Myocardial Infarction

Intervention / Treatment
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* Drug: Autologous hMSCs
* Drug: Autologous Human C-Kit CSCs II
* Drug: Placebo
* Device: Biosense Webster MyoStar NOGA Injection Catheter System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to participate in this study, a patient MUST: Be ≥ 21 and < 90 years of age. Provide written informed consent. Have a diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by the following: Screening MRI must show an area of akinesis, dyskinesis, or severe hypokinesis associated with evidence of myocardial scarring based on delayed hyperenhancement following gadolinium infusion. Been treated with appropriate maximal medical therapy for heart failure or post-infarction left ventricular dysfunction. For beta-blockade, the patient must have been on a stable dose of a clinically appropriate beta-blocker for 3 months. For angiotensin-converting enzyme inhibition, the patient must have been on a stable dose of a clinically appropriate agent for 1 month. Be a candidate for cardiac catheterization. Have an ejection fraction ≤ 50% by gated blood pool scan, two-dimensional echocardiogram, cardiac MRI, or left ventriculogram within the prior six months and not in the setting of a recent ischemic event. Exclusion Criteria: In order to participate in this study, a patient MUST NOT: Have a baseline glomerular filtration rate < 50 ml/min1.73m2. Have a known, serious radiographic contrast allergy. Have a mechanical aortic valve or heart constrictive device. Have a documented presence of aortic stenosis (aortic stenosis graded as ≥ +2 equivalent to an orifice area of 1.5cm2 or less). Have a documented presence of moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥+2). Require coronary artery revascularization. Patients who require or undergo revascularization procedures should undergo these procedures a minimum of 3 months in advance of treatment within this study. In addition, patients who develop a need for revascularization following enrollment will be submitted for this therapy without delay. Evidence of a life-threatening arrhythmia (nonsustained ventricular tachycardia ≥ 20 consecutive beats or complete heart block) or QTc interval > 550 ms on screening ECG. AICD firing in the past 60 days prior to the procedure. Have unstable angina within 2 weeks of the planned procedure. Have a hematologic abnormality as evidenced by hematocrit < 25%, white blood cell < 2,500/ul or platelet values < 100,000/ul without another explanation. Have liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN. Have a coagulopathy = (INR > 1.3) not due to a reversible cause (i.e., Coumadin). Patients on Coumadin will be withdrawn 5 days before the procedure and confirmed to have an INR < 1.3. Patients who cannot be withdrawn from Coumadin will be excluded from enrollment Have known allergies to penicillin or streptomycin. Have a contra-indication to performance of an MRI scan. Be an organ transplant recipient. Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma. Have a non-cardiac condition that limits lifespan to < 1 year. Have a history of drug or alcohol abuse within the past 24 months. Be on chronic therapy with immunosuppressant medication, such as corticosteroids or TNFα antagonists. Be serum positive for HIV, hepatitis BsAg or hepatitis C. Be currently participating (or participated within the previous 30 days) in an investigational therapeutic or device trial. Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraceptive methods. Female patients must undergo a blood or urine pregnancy test at screening and within 36 hours prior to injection.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A - Autologous hMSCs<br>Autologous hMSCs: 40 million cells/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 2 x 10^8 (200 million) hMSCs. The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug. | Drug: Autologous hMSCs<br>* Autologous hMSCs: 40 million cells/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 2 x 10^8 (200 million) hMSCs.<br>* Other names: Autologous Human Mesenchymal Stem Cells (hMSCs);Device: Biosense Webster MyoStar NOGA Injection Catheter System<br>* Biosense Webster MyoStar NOGA Injection Catheter System will be used to administer the study drug<br>* Other names: NOGA;|
| Experimental: Group B - Autologous Human C-Kit CSCs II<br>Autologous hMSCs PLUS autologous C-Kit hCSCs: Mixture of 39.8 million hMSCs and 0.2 million C-Kit hCSCs/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 1.99 x 10^8 (199 million) hMSCs and 1 million C-Kit hCSCs.The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug. | Drug: Autologous Human C-Kit CSCs II<br>* Autologous hMSCs PLUS autologous C-Kit hCSCs: Mixture of 39.8 million hMSCs and 0.2 million C-Kit hCSCs/ml delivered in 0.5 ml injection volumes times 10 injections for a total of 1.99 x 10^8 (199 million) hMSCs and 1 million C-Kit hCSCs.<br>* Other names: Autologous Human C-Kit Cardiac Stem Cells (CSCs) II;Device: Biosense Webster MyoStar NOGA Injection Catheter System<br>* Biosense Webster MyoStar NOGA Injection Catheter System will be used to administer the study drug<br>* Other names: NOGA;|
| Placebo Comparator: Placebo<br>Placebo (ten 0.5 ml injections of phosphate-buffered saline [PBS] and 1% human serum albumin [HSA]).The Biosense Webster MyoStar NOGA Injection Catheter System will be used in the delivery of the study drug. | Drug: Placebo<br>* Placebo (ten 0.5 ml injections of phosphate-buffered saline [PBS] and 1% human serum albumin [HSA]).<br>Device: Biosense Webster MyoStar NOGA Injection Catheter System<br>* Biosense Webster MyoStar NOGA Injection Catheter System will be used to administer the study drug<br>* Other names: NOGA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of any treatment emergent serious adverse events (TE-SAEs) | Incidence (at one month post-catheterization) of any treatment-emergent serious adverse events (TE-SAEs), defined as the composite of: death, non-fatal MI, stroke, hospitalization for worsening heart failure, cardiac perforation, pericardial tamponade, sustained ventricular arrhythmias (characterized by ventricular arrhythmias lasting longer than 15 seconds or with hemodynamic compromise), or atrial fibrillation. | One Month post-catheterization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent adverse event rates | Rate of adverse events occurring ad | At 6 Month and 12 Month visit | 
| Ectopic tissue formation | Ectopic tissue formation (as identified from MRI scans of the chest, abdomen, & pelvis). | At 6 Month and 12 Month visit | 
| 48-hour ambulatory electrocardiogram (ECG) recordings. | Electrocardiogram (ECG) recordings measured over 48 Hours | At 6 Month and 12 Month visit | 
| Hematology value changes post-catheterization | Hematology value changes will be observed at the 6 month and 12 month visit post-catheterization. | At 6 Month and 12 Month visit | 
| Urinalysis results changes post-catheterization | Urinalysis results changes will be observed at the 6 month and 12 month visit post-catheterization. | At 6 Month and 12 Month visit | 
| Clinical chemistry values post-catheterization | Clinical chemistry value changes will be observed at the 6 month and 12 month visit post-catheterization. | At 6 Month and 12 Month visit | 
| Pulmonary function | Pulmonary function - forced expiratory volume in 1 second (FEV1) results. | At 6 Month and 12 Month visit | 
| Serial troponin I values | Serial troponin I values (every 12 hours for first 48 hours post-cardiac catheterization). | Every 12 hours for the first 48 hours post-cardiac catheterization | 
| Creatine kinase-MB (CK-MB) value changes post-catheterization | CK-MB values (every 12 hours for first 48 hours post-cardiac catheterization). | Every 12 hours for first 48 hours post-cardiac catheterization | 
| Post-cardiac catheterization echocardiogram. | Echocardiogram performed after cardiac catheterization | Day 1 Post Echocardiogram | 
| Magnetic resonance imaging (MRI) measures of infarct scar size (ISS) | Document Infarct Scar Size (ISS) via Magnetic Resonance imaging (MRI) | At 6 Month and 12 Month visit | 
| Echocardiographic measures of infarct scar size (ISS) | Document Infarct Scar Size (ISS) via echocardiographic procedure | At 6 Month and 12 Month visit | 
| Magnetic resonance imaging (MRI) of Left Regional Ventricular Function | Document Left Regional Ventricular Function via Magnetic Resonance imaging (MRI) | At 6 Month and 12 Month visit | 
| Echocardiographic measures of Left Regional Ventricular Function | Document Left Regional Ventricular Function via echocardiographic procedure | At 6 Month and 12 Month visit | 
| Magnetic resonance imaging (MRI) of Global Ventricular Function | Document Global Ventricular Function via Magnetic Resonance imaging (MRI) | At 6 Month and 12 Month visit | 
| Echocardiographic measures of Global Ventricular Function | Document Global Ventricular Function via echocardiographic procedure | At 6 Month and 12 Month visit | 
| Tissue perfusion measured by MRI. | Measure Tissue Perfusion via Magnetic Resonance imaging (MRI) | At 6 Month and 12 Month visit | 
| Peak oxygen consumption (Peak VO2) (by treadmill determination). | Peak VO2 Oxygen Consumption determined by utilizing treadmill | At 6 Month and 12 Month visit | 
| Six-minute walk test. | Evaluate Functional Capacity via the Six Minute Walk Test | At 6 Month and 12 Month visit | 
| New York Heart Association (NYHA) functional class. | Evaluate Functional Capacity via New York Heart Association (NYHA) Class Determination | At 6 Month and 12 Month visit | 
| Minnesota Living with Heart Failure (MLHF) questionnaire. | Evaluate Quality Of Life Changes via Minnesota Living with Heart Failure (MLHF) Questionnaire | At 6 Month and 12 Month visit | 
| Incidence of Major Adverse Cardiac Events (MACE) | Incidence of Major Adverse Cardiac Events (MACE), defined as the composite incidence of (1) death, (2) hospitalization for worsening HF, or (3) non-fatal recurrent MI. | At 6 Month and 12 Month visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular, Secondary