Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy

This study has been completed.
Sponsor:
Collaborator:
Hospital Universitario Reina Sofia
Information provided by (Responsible Party):
Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier:
NCT00629096
First received: February 25, 2008
Last updated: May 9, 2013
Last verified: May 2013
  Purpose

The main aim of the study is to determine whether intracoronary infusion of autologous bone marrow mononuclear cells can improve the ventricular function of patients with idiopathic dilated cardiomyopathy.Secondary end-points will be:

  1. To evaluate possible changes in patient functional capacity and
  2. to identify the biological characteristics of the bone marrow graft that might influence on functional recovery.

Condition Intervention Phase
Dilated Cardiomyopathy
Procedure: Intracoronary infusion of autologous bone marrow cells
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Intracoronary Infusion of Bone Marrow-derived Progenitor Cells on Myocardial Regeneration in Patients With Non-ischemic Dilated Cardiomyopathy.

Resource links provided by NLM:


Further study details as provided by Fundación Pública Andaluza Progreso y Salud:

Primary Outcome Measures:
  • Improvement of left ventricular function [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Functional status [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: February 2008
Study Completion Date: December 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
All included patients are assigned to arm 1, in which they are treated by the intervention
Procedure: Intracoronary infusion of autologous bone marrow cells
Autologous mononuclear bone marrow cells will be administered by intracoronary infusion via a percutaneous catheter

  Hide Detailed Description

Detailed Description:

Clinical studies have shown that bone marrow cells can regenerate damaged myocardium after ischemic cardiopathy; however scarce information is available from patients with non-ischemic dilated cardiomyopathy. The aim of the present work is to investigate the role of intracoronary infusion of autologous marrow-derived stem cells in a phase II study in 30 patients with dilated cardiomyopathy.Before the intracoronary transplant of marrow cells as well as six and twelve months thereafter, we will compare the ventricular function measured as left-ventricular ejection fraction by angiography, magnetic resonance imaging, echocardiography and treadmill direct oxygen consumption test. Functional capacity will be monitored throughout the study. In every condition of the study we will perform at least one 30º right anterior oblique left ventricle (LV)angiogram. During each ventriculogram, attempts will be made to obtain a sinus and a post-extrasystolic beat for analysis, in order to study contractile reserve behaviours. Post-extrasystolic beats will be obtained by inducing premature beats with the catheter, once a well opacified cardiac cycle with a normal sinus beat had been filmed. In all instances, the r-r' interval of the induced premature beat and the post-extrasystolic pause will be recorded and measured.

Measurements and calculations will be made off line in our own core lab, where end-diastolic and end-systolic silhouettes were drawn using the CASS system by 2 expert angiographers who were unaware of the patient group or study conditions. LV-volumes and ejection fraction (EF) were derived and regional wall motion was analyzed. The method by Sheehan (1) was used for the asynergy study, dividing the superimposed silhouettes in 100 radii of wall shortening, from end-diastole to end-systole. The abnormal contracting segment (ACS) was defined as the percentage of radii showing akinesia or dyskinesia. The areas of the ventrivular walls having asynergy will be regionally evaluated. The serial evolution of the contractile reserve will be evaluated by the post-extrasystolic potentiation.

Coronary Flow Reserve (CFR) in all 3 coronary arteries will also be evaluated during every hemodynamic study (before treatment and 6 months after treatment). The FloMap® system (Cardiometrics; Mountain View; California) will be used. A 0.014" intracoronary Doppler guide wire will be positioned proximally in every coronary and flow velocities will be recorded continuously. Average peak velocity will be obtained at baseline and after an intracoronary bolus of Adenosine. CFR will be calculated as the ratio between maximal flow velocity during the peak effect of the adenosine injection and basal flow velocity.

Magnetic Resonance Image (MRI) studies will be performed in 3 conditions (baseline, 3-month and 1-year after treatment). Functional parameters will be obtained in each condition, including LV-volumes, LV-mass and ejection fraction

On the morning of cardiac catheterization, up to a volume of 100-150 ml of marrow will be obtained under local anesthesia by aspiration from the iliac crest. Mononuclear Bone Marrow Cells (MNBMCs) will be isolated by density gradient centrifugation over Ficoll-Hypaque technique in a sterile, semiautomated device COBE® 2991. After three washes, MNBMCs will be filtered and resuspended in 10 ml of 0.9% sodium chloride supplemented with preservative-free 0.1% heparin. Aliquots will be obtained for cell count as well as for cytofluorometric and functional analyses of the cell content.

Cells will be directly transferred to all 3 coronary arteries (50% to left anterior descending artery, 25% to the circumflex and 25% to the right coronary artery) by the use of a coaxial balloon catheter, which will be placed proximally at each artery. Balloon size will be selected according to vessel size, in order to achieve complete occlusion of the vessel and to stop flow during cell injection. So, backflow of cells is prevented and distal stagnant flow will facilitate cell exposure. The cell suspension will be injected through the distal tip of the balloon over 2 to 4 minutes.

In addition,we will try to compare all possible changes in functional parameters with biological variables obtained from the marrow graft, such as:

  1. Number of cells positive for cluster of differentiation antigen (CD) CD146,CD31, CD133,CD90,CD38, CD117, CD73, CD105, CD45, Vascular endothelial growth factor receptor 2,CXC-chemokine receptor 4 and HLA-DR.
  2. Functional characterization of endothelial progenitor cells and mesenchymal stem cells present in the graft by in vitro selective cultures.
  3. Analysis of the in vitro chemotactic ability of the infused cells.
  4. Determination of lineage-specific cardiac markers GATA-4 and Nk2.5/Csx in the infused marrow-derived cells. Correlations between these biological parameters and the effects on patient`s ventricular function could highlight the role of each of the potential mechanisms implied in cell-mediated myocardial regeneration.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients of both genders with established clinical and angiographic diagnosis of Idiopathic Dilated Cardiomyopathy who accept to participate in the trial.
  2. They should have symptoms and/or signs of heart failure, despite optimized medical treatment.
  3. Angiographic ejection fraction should be less than 50%.

Exclusion Criteria:

  1. Associated coronary artery disease.
  2. Any history or suspicion of a toxic, pharmacologic or deposit etiology.
  3. Absence of resynchronization therapy.
  4. Age longer than 80 years.
  5. Associated malignant or pre-malignant systemic disease.
  6. Associated hematologic disorder.
  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: NCT00629096

Locations
Spain
Reina Sofía University Hospital
Córdoba, Spain, 14004
Sponsors and Collaborators
Fundación Pública Andaluza Progreso y Salud
Hospital Universitario Reina Sofia
Investigators
Study Chair: Jose Suarez de Lezo, MD, PhD Department of Cardiology. Reina Sofía University Hospital
Study Director: I. Concepción Herrera, MD, PhD Department of Hematology.Reina Sofia University Hospital
Principal Investigator: Manuel Pan, MD, PhD Department of Cardiology. Reina sofia University Hospital
Principal Investigator: Jose Maria Arizon, MD Department of Cardiology. Reina Sofía university Hospital
Principal Investigator: Miguel Angel Romero, MD, PhD Department of Cardiology. Reina Sofía University Hospital
Principal Investigator: Ramon Ribes, MD, PhD Department of Radiology. Reina Sofía University Hospital
Principal Investigator: Joaquin Sanchez, MD, PhD Department of Hematology. Reina Sofía Unuversity Hospital
Principal Investigator: Antonio Torrers, MD, PhD Department of Hematology. Reina Sofía University Hospital
  More Information

No publications provided

Responsible Party: Fundación Pública Andaluza Progreso y Salud
ClinicalTrials.gov Identifier: NCT00629096     History of Changes
Other Study ID Numbers: TCMR0007/2006, EudraCT 2007-003088-36
Study First Received: February 25, 2008
Last Updated: May 9, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Fundación Pública Andaluza Progreso y Salud:
Dilated Cardiomyopathy
Marrow stem cells
Myocardial regeneration
Mesenchymal stem cells
Marrow-derived endothelial progenitor cells

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

ClinicalTrials.gov processed this record on September 18, 2014