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

Phase 2

Completed

• Conditions: Chronic Heart Failure; Dilated Cardiomyopathy
• Interventions: Procedure: Intramyocardial injection; Procedure: Intracoronary injection

• Registration Number: NCT01350310
• Lead Sponsor: University Medical Centre Ljubljana

Brief Summary

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.

1. To evaluate safety and efficacy of intramyocardial stem cell therapy in patients with non-ischemic dilated cardiomyopathy.

2. 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.

1. 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.

2. Beneficial effects of intramyocardial stem cell therapy will be superior to those observed with intracoronary stem cell delivery.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-05-06
• Study First Submitted QC: 2011-05-06
• Study First Posted: 2011-05-09
• Primary Completion: 2014-08
• Study Completion: 2014-12
• Status Verified: 2015-04
• Last Update Submitted: 2015-04-05
• Last Update Posted: 2015-04-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intramyocardial Injections	Intramyocardial injection	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.
Intracoronary Injections	Intracoronary injection	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.
Ischemic heart disease	Intramyocardial injection	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

Primary Outcome Measures

Name	Time	Method
Changes in left ventricular ejection fraction and dimensions	1 year	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

UMC Ljubljana; 🇸🇮 Ljubljana, Slovenia