Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy (NOGA-DCM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by University Medical Centre Ljubljana
Sponsor:
Collaborators:
The Methodist Hospital System
Stanford University
Information provided by (Responsible Party):
Bojan Vrtovec, University Medical Centre Ljubljana
ClinicalTrials.gov Identifier:
NCT01350310
First received: May 6, 2011
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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.

Condition Intervention Phase
Dilated Cardiomyopathy
Chronic Heart Failure
Procedure: Intramyocardial injection
Procedure: Intracoronary injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy

Resource links provided by NLM:


Further study details as provided by University Medical Centre Ljubljana:

Primary Outcome Measures:
  • Changes in left ventricular ejection fraction and dimensions [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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:
  • Changes in exercise capacity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Exercise capacity will be evaluated with 6-minute walk test at baseline, and again at 1,3,6 and 12 months after the procedure.

  • Change in NT-proBNP levels [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Plasma levels of NT-proBNP will be measured at baseline, and again at 1, 3, 6 and 12 months after the procedure.


Estimated Enrollment: 90
Study Start Date: March 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intramyocardial Injections
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
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).
Active Comparator: Intracoronary Injections
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
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.
Active Comparator: Ischemic heart disease
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
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).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01350310

Contacts
Contact: Bojan Vrtovec, MD, PhD +3861 522 1148 bojan.vrtovec@gmail.com
Contact: Gregor Poglajen, MD gregor.poglajen@gmail.com

Locations
Slovenia
UMC Ljubljana Recruiting
Ljubljana, Slovenia, 1000
Principal Investigator: Bojan Vrtovec, MD, PhD         
Sub-Investigator: Matjaž Sever, MD         
Sub-Investigator: Luka Ležaič, MD         
Sub-Investigator: Dragoslav Domanovic, MD, PhD         
Sub-Investigator: Gregor Poglajen, MD         
Sub-Investigator: Miran Šebeštjen, MD, PhD         
Sub-Investigator: Renata Okrajšek, MD, PhD         
Sponsors and Collaborators
University Medical Centre Ljubljana
The Methodist Hospital System
Stanford University
  More Information

No publications provided by University Medical Centre Ljubljana

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bojan Vrtovec, Prof. Dr. Bojan Vrtovec, dr. med., University Medical Centre Ljubljana
ClinicalTrials.gov Identifier: NCT01350310     History of Changes
Other Study ID Numbers: NOGA-DCM
Study First Received: May 6, 2011
Last Updated: April 9, 2013
Health Authority: Slovenia: Ethics Committee

Keywords provided by University Medical Centre Ljubljana:
Heart failure
Dilated cardiomyopathy
Stem cells

Additional relevant MeSH terms:
Cardiomyopathy, Dilated
Heart Failure
Cardiomyopathies
Cardiomegaly
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 28, 2014