Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy

Study Overview
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Brief Summary
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BACKGROUND. In patients with non-ischemic dilated cardiomyopathy, intracoronary stem cell transplantation has been shown to improve exercise capacity, reduce ventricular remodelling and improve 1-year survival. Pre-clinical data demonstrate that stem cell effects on the diseased heart can be further enhanced by direct intramyocardial delivery route. AIMS. To evaluate safety and efficacy of intramyocardial stem cell therapy in patients with non-ischemic dilated cardiomyopathy. To directly compare clinical effects of intracoronary and intramyocardial stem cell delivery. METHODS. Of 60 patients with dilated cardiomyopathy, 30 will be randomized to intramyocardial transplantation of CD34+ cells (Study Group), and 30 will receive intracoronary stem cell therapy (Control Group). In both groups peripheral blood stem cells will be mobilised by daily subcutaneous injections of filgrastim; CD34+ cells will be collected via apheresis and labelled with technetium. In the Study Group electromechanical mapping will be used to identify viable myocardium and intramyocardial injections in the target areas will be performed with NOGA catheter. In the Control group patients will undergo myocardial perfusion scintigraphy and CD34+ cells will be injected intracoronary in the artery supplying segments of reduced viability. Patients will be followed for 1 year. Primary endpoints will include changes in left ventricular ejection fraction and left ventricular dimensions (measured by echocardiography). Secondary endpoints will include changes in exercise capacity and changes in NT-proBNP values. HYPOTHESES. At 1 year, intramyocardial stem cell therapy will be associated with improved left ventricular ejection fraction, reduced left ventricular dimensions, improved exercise capacity and reduced levels of NT-proBNP. Beneficial effects of intramyocardial stem cell therapy will be superior to those observed with intracoronary stem cell delivery.

Official Title
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Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy

Conditions
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Dilated Cardiomyopathy, Chronic Heart Failure

Intervention / Treatment
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* Procedure: Intramyocardial injection
* Procedure: Intracoronary injection
* Procedure: Intramyocardial injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established dg. of dilated CMP (defined according to ESC position statement - absence of any stenotic lesions on coronary angiography, no congenital heart disease, no primary valve disease on echocardiography, and no history of hypertension or alcohol abuse1) left ventricular ejection fraction < 30% NYHA functional class III or IV for at least 3 months before referral Optimal medical management for at least 6 months Exclusion Criteria: Left ventricular aneurysm or thrombus Hematologic disease Multiorgan failure Active malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Intramyocardial Injections<br>Peripheral blood stem cells will be mobilised by daily subcutaneous injections of filgrastim; CD34+ cells will be collected via apheresis and labelled with technetium. Electromechanical mapping will be used to identify viable myocardium and intramyocardial injections in the target areas will be performed with NOGA catheter. Nuclear imaging for quantitation of myocardial retention rates of labeled cells will be performed at 2 and 18 hours after the procedure. | Procedure: Intramyocardial injection<br>* Electromechanical mapping will be used to identify viable myocardium (unipolar voltage >6.9 mV) and intramyocardial injections in the target areas will be performed with NOGA catheter (25 injections of 0.3 cc).<br>|
| Active Comparator: Intracoronary Injections<br>Peripheral blood stem cells will be mobilised by daily subcutaneous injections of filgrastim; CD34+ cells will be collected via apheresis and labelled with technetium. Patients will undergo myocardial perfusion scintigraphy and CD34+ cells will be injected intracoronary in the artery supplying segments of reduced viability. Nuclear imaging for quantitation of myocardial retention rates of labeled cells will be performed at 2 and 18 hours after the procedure. | Procedure: Intracoronary injection<br>* Patients will undergo myocardial perfusion scintigraphy for myocardial viability assessment. Microcatheter will be placed in the mid segment of the coronary artery supplying the segments of reduced tracer accumulation and repeated intracoronary injections of stem cell solution will be performed.<br>|
| Active Comparator: Ischemic heart disease<br>Peripheral blood stem cells will be mobilised by daily subcutaneous injections of filgrastim; CD34+ cells will be collected via apheresis and labelled with technetium. Electromechanical mapping will be used to identify viable myocardium and intramyocardial injections in the target areas will be performed with NOGA catheter. Nuclear imaging for quantitation of myocardial retention rates of labeled cells will be performed at 2 and 18 hours after the procedure | Procedure: Intramyocardial injection<br>* Procedure/Surgery: Intramyocardial injection Electromechanical mapping will be used to identify viable myocardium (unipolar voltage >6.9 mV) and intramyocardial injections in the target areas will be performed with NOGA catheter (25 injections of 0.3 cc).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in left ventricular ejection fraction and dimensions | Standard 2D and Doppler echocardiography will be performed at baseline, and repeated at 1 month, 3 months, 6 months and 1 year after the procedure. Left ventricular ejection fraction will be measured using Simpson's method and left ventricular end-systolic and end-diastolic dimensions will be measured according to standard echocardiography protocol. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in exercise capacity | Exercise capacity will be evaluated with 6-minute walk test at baseline, and again at 1,3,6 and 12 months after the procedure. | 1 year | 
| Change in NT-proBNP levels | Plasma levels of NT-proBNP will be measured at baseline, and again at 1, 3, 6 and 12 months after the procedure. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Dilated cardiomyopathy, Stem cells