METHOD - Bone Marrow Derived Mononuclear Cells in Chronic Ischemic Disease

Study Overview
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Brief Summary
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Intramyocardial, NOGA guided injection of bone marrow derived mononuclear cells in patients with chronic ischemic heart disease and LVEF < 40%. The primary objective is to determine whether the administration of the cells improves recovery of the left ventricular function. Secondary objective is the finding of clinical or paraclinical parameters to predict potential benefits of the treatment (basing on MRI characteristics such as size, transmurality of the myocardial infarction and peri-lesional ischemia). In the first part of the study 10 patients are treated without control group. This phase serves as feasibility and safety part of the study.

Official Title
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METHOD - Phase I/II Study of Intramyocardial Injection of Bone Marrow Derived Mononuclear Cells in Chronic Ischemic Disease

Conditions
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Chronic Ischemic Heart Disease

Intervention / Treatment
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* Other: intramyocardial injection of BM cells
* Other: intramyocardial / intracoronary injection of BM cells
* Other: Best medical therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic cardiac ischemic disease at least 4 months after one ore more myocardial infarctions in a stable phase of the disease without option for revascularization LVEF at echocardiography ≤ 40% Significant regional LV wall motion dysfunction in the infarct related territory Symptoms NYHA II-IV or CCS II-III (at least class III according to one of the two classifications) Patient agrees to comply with all follow-up evaluations Age > 18 years old Patient has been informed of the nature of the clinical trial and agrees to its provision and has provided written informed consent Exclusion Criteria: Abnormal regional wall motion outside the infarct region Need for revascularization in a non infarct-related coronary within 6 months Patient has moderate to severe aortic valve disease, aortic or mitral prosthetic valve Patient has a significant mitral valve insufficiency (Effective Regurgitant office - ERO - > 0.2 cm2 with possibility of mitral valve surgery Left ventricular thrombus at echocardiography LV-aneurysma planned surgical aneurysmectomy LV-wall thickness < 5mm in the target territory Congenital heart disorder of hemodynamic relevance Known active infection or chronic infection with HIV, HBV or HCV Chronic inflammatory disease Serious concomitant disease with a life expectancy of less than one year Follow up impossible (no fixed abode, etc) Contraindication for cardiac MRI (i.e. pace maker, neurostimulator, claustrophobia) Severe renal failure (creatinine > 250 mmol/l) Relevant liver disease (GOT > 2x norm or spontaneous INR > 1,5) Anemia (Hb < 8.5 mg/dl), Thrombocytopenia (< 100.000/µl) Women of child bearing potential or pregnancy Participation at a clinical trial in the last 30 days

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intramyocardial injection of BM cells<br> | Other: intramyocardial injection of BM cells<br>* only intramyocardial, NOGA guided injection on BM cells.<br>|
| Experimental: Intramyocardial / intracoronary injection of BM cells<br> | Other: intramyocardial / intracoronary injection of BM cells<br>* combination of intramyocardial, NOGA guided injection of BM cells and intracoronary injection of those cells<br>|
| Other: control<br> | Other: Best medical therapy<br>* initially no intervention; crossover to therapy 6 months after enrollment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Troponin samples | Measurements of Troponine after cell injection | 1 day after cell injection | 
| Number of patients with adverse events at short term |  | within 1 week after cell injection | 
| Number of patients with adverse events at mid/long term |  | up to 12 months after cell injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in LVEF | First 10 patients + following randomization phase (n = 54); assessment of short term safety (1 week), Adverse events within 1 year; efficacy measurements 6 months after treatment | 6 months vs. baseline | 
| change in Quality of life |  | 6 months vs. baseline | 
| change in Vo2 max | change in functional status (Vo2 max) | 6 months vs. bl | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LVEF < 40%