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

Chronic Heart Failure Clinical Trial

— NOGA-DCM  

Official title:

Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01350310
• Other study ID #: NOGA-DCM
• Status: Completed
• Phase: Phase 2
• First received: May 6, 2011
• Last updated: April 5, 2015
• Start date: March 2011
• Est. completion date: December 2014

Study information

• Verified date: April 2015
• Source: University Medical Centre Ljubljana
• Contact: n/a
• Is FDA regulated: No
• Health authority: Slovenia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: December 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Chronic Heart Failure
• Dilated Cardiomyopathy
• Heart Failure

Intervention

Procedure:
• 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).
• Intracoronary injection
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.
• Intramyocardial injection
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).

Locations

Country	Name	City	State
Slovenia	UMC Ljubljana	Ljubljana

Sponsors (3)

Lead Sponsor	Collaborator
University Medical Centre Ljubljana	Stanford University, The Methodist Hospital System

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	Yes