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

• ClinicalTrials.gov Identifier: NCT01350310
• Recruitment Status: Completed
• First Posted: May 9, 2011
• Last Update Posted: April 7, 2015
• Sponsor: University Medical Centre Ljubljana
• Collaborators: The Methodist Hospital System; Stanford University
• Information provided by (Responsible Party): Bojan Vrtovec, University Medical Centre Ljubljana

Tracking Information

• First Submitted Date: May 6, 2011
• First Posted Date: May 9, 2011
• Last Update Posted Date: April 7, 2015
• Study Start Date: March 2011
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2011)

Changes in left ventricular ejection fraction and dimensions [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01350310 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: May 6, 2011)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
• Official Title: Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy

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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Dilated Cardiomyopathy
• Chronic 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).
• 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.
• 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).

Study Arms

• 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.
  Intervention: Procedure: Intramyocardial injection
• 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.
  Intervention: Procedure: Intracoronary injection
• 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
  Intervention: Procedure: Intramyocardial injection

Publications *

• Lezaic L, Socan A, Poglajen G, Peitl PK, Sever M, Cukjati M, Cernelc P, Wu JC, Haddad F, Vrtovec B. Intracoronary transplantation of CD34(+) cells is associated with improved myocardial perfusion in patients with nonischemic dilated cardiomyopathy. J Card Fail. 2015 Feb;21(2):145-52. doi: 10.1016/j.cardfail.2014.11.005. Epub 2014 Nov 18.
• Poglajen G, Sever M, Cukjati M, Cernelc P, Knezevic I, Zemljic G, Haddad F, Wu JC, Vrtovec B. Effects of transendocardial CD34+ cell transplantation in patients with ischemic cardiomyopathy. Circ Cardiovasc Interv. 2014 Aug;7(4):552-9. doi: 10.1161/CIRCINTERVENTIONS.114.001436. Epub 2014 Aug 5.
• Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, Cernelc P, Torre-Amione G, Haddad F, Wu JC. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013 Sep 10;128(11 Suppl 1):S42-9. doi: 10.1161/CIRCULATIONAHA.112.000230.
• Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, Socan A, Schrepfer S, Torre-Amione G, Haddad F, Wu JC. Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res. 2013 Jan 4;112(1):165-73. doi: 10.1161/CIRCRESAHA.112.276519. Epub 2012 Oct 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 5, 2015): 110
• Original Estimated Enrollment (submitted: May 6, 2011): 60
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Slovenia

Administrative Information

• NCT Number: NCT01350310
• Other Study ID Numbers: NOGA-DCM
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bojan Vrtovec, University Medical Centre Ljubljana
• Study Sponsor: University Medical Centre Ljubljana

Collaborators

• The Methodist Hospital System
• Stanford University

• Investigators: Not Provided
• PRS Account: University Medical Centre Ljubljana
• Verification Date: April 2015