Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Hospital General Universitario Gregorio Marañon
Sponsor:
Collaborator:
Ministerio de Sanidad, Servicios Sociales e Igualdad
Information provided by (Responsible Party):
Hospital General Universitario Gregorio Marañon
ClinicalTrials.gov Identifier:
NCT01957826
First received: December 21, 2012
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to assess the safety, the feasibility and the efficacy of transendocardial injection of bone marrow-derived mesenchymal stem cells (MSCs) in patients with dilated idiopathic cardiomyopathy.


Condition Intervention Phase
Primary Idiopathic Dilated Cardiomyopathy
Other: bone marrow-derived MSCs injection
Other: placebo intervention
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase I/II Randomized Clinical Trial to Assess the Safety and Feasibility of Transendocardial Injection of Bone Marrow Autologous Mesenchymal Stem Cells in Patients With Idiopathic Dilated Cardiomyopathy.

Resource links provided by NLM:


Further study details as provided by Hospital General Universitario Gregorio Marañon:

Primary Outcome Measures:
  • Major adverse cardiac adverse events. SAEs and AEs. [ Time Frame: change from enrollment( 1, 3, 6, 12, 18 and 24 months) ] [ Designated as safety issue: Yes ]
    Major adverse cardiac adverse events includes cerebral adverse events

  • NYHA functional class. [ Time Frame: Change from enrolment( 1, 3, 6, 12, 18, 24 months) ] [ Designated as safety issue: Yes ]
  • Incidence of complications with the use of NOGA XPTM catheters. [ Time Frame: Change from enrolment( 1, 3, 6, 12, 18, 24 months) ] [ Designated as safety issue: Yes ]
  • Laboratory parameters including C-reactive protein an brain natriuretic peptide [ Time Frame: Change from enrolment( 1, 3, 6, 12, 18, 24 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • NYHA Functional Class [ Time Frame: 1, 3, 6, 12, 18, 24 months ] [ Designated as safety issue: No ]
  • Max.oxygen consumption(MVO2),functional capacity. [ Time Frame: 6,12,24 months ] [ Designated as safety issue: No ]
  • Quality of life questionnaires [ Time Frame: 6,12 and 24 months ] [ Designated as safety issue: No ]
    include 36-item Short Form Survey(SF 36) and Minnesota Living UIT Heart Failure questionnaire

  • Extension. of perfusion defects(MRI/SPECT). [ Time Frame: 6 and 24 months ] [ Designated as safety issue: No ]
  • LVEF, ventricular vol.,wall motion score index(echocard./MRI/SPECT [ Time Frame: 6,12 and 24 months ] [ Designated as safety issue: No ]
  • LVEF(left ventriculogram, electromech. mapping parameters(NOGA XPTM)) [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: March 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo comparator
transendocardial injection of placebo solution
Other: placebo intervention
placebo administration
Experimental: bone marrow-derived MSCs injection
transendocardial injection of 30-40 million bone marrow-derived MSCs with the NOGA XPTM platform. 15 injections in the anterior wall of the left ventricle.
Other: bone marrow-derived MSCs injection
transendocardial injection of 30-40 million bone marrow-derived MSCs with the NOGA XPTM platform. 15 injections in the anterior wall of the left ventricle.

Detailed Description:

Chronic congestive heart failure (CHF) is a public health problem that entails high rates of morbidity and mortality, and enormous costs for health systems worldwide. In the United States there are 5 million people living with CHF, and each year 60.000 people reach terminal phases of the disease, with mortality rates of 70-80% at two years. Although the first cause of CHF in developed countries is atherosclerotic coronary artery disease (CAD), dilated idiopathic cardiomyopathy (DCM) represents almost half of the cases of newly diagnosed CHF. Treatment of CHF includes pharmacological and non-pharmacological strategies, including implantable cardioverter defibrillators, cardiac resynchronization therapy and heart transplantation. Despite all these advances, CHF prognosis remains poor. Cardiac stem cell therapy emerged more than ten years ago as a new hope for CHF patients.

Although the most extensive evidence of the benefits of stem cell therapy for cardiovascular diseases refers to ischemic heart disease (CAD), initial experiences with stem cells for other conditions such as DCM are encouraging.

This randomized clinical trial will include 70 patients with DCM, left ventricular ejection fraction (LVEF) between 20% and 45%, and who are symptomatic in New York Heart Association (NYHA) functional class II-III/IV. In a first-in-man pilot phase, 10 patients will be treated with transendocardial injections of bone marrow-derived MSCs after cardiac catheterization and NOGA XPTM mapping of the left ventricle. A Data and Safety Monitoring Board (DSMB) will analyse the safety and feasibility of this first phase of the trial, and then 60 patients more will be randomized to receive MSCs or placebo (ratio 3:1).

Primary objectives include safety and feasibility variables, and secondary objectives include efficacy variables. All patients will be studied with a complete cardiac imaging protocol that includes: electrocardiography, echocardiography, treadmill tests with oxygen consumption, holter, laboratory analyses, magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), electromechanical mapping (NOGA XPTM) and quality of life questionnaires.

  Eligibility

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

Inclusion Criteria:

  • II-III NYHA functional class, under optimal medical therapy.
  • LVEF ≥ 20% and ≤ 45% by echocardiography, SPECT or left ventriculogram one month prior to enrollment.
  • Anterior wall thickness ≥ 8 mm by echocardiography or MRI one month prior to enrollment.
  • Idiopathic DCM diagnosis (having excluded CAD, valvular heart disease, cardiac toxic drugs, tachyarrhythmias, metabolic diseases, systemic diseases, infectious diseases) six months prior to enrollment.
  • Patients rejected for heart transplantation should have been discussed in the Heart Team at their respective centres, and a document stating the reason for exclusion will be kept in the medical record.
  • Able to exercise on a treadmill, MVO2 between ≥ 12 and ≤ 21 ml/Kg/min.
  • Hemodynamic stability (blood pressure > 100/40 mmHg, heart rate < 110 bpm and oxygen saturation > 95%).
  • Negative pregnancy test in women.
  • Signed informed consent

Exclusion Criteria:

  • Evidence of secondary dilated cardiomyopathy causes: CAD, valvular heart disease, cardiac toxic drugs, tachyarrhythmias, metabolic diseases, systemic diseases, infectious diseases, myocarditis or postpartum ventricular dysfunction.
  • Permanent atrial fibrillation.
  • Candidates for ICD or CRT devices. Patients with theses devices can be enrolled if the device has been implanted at least 6 months before inclusion, and only if no-response has been observed to CRT.
  • Candidates for heart transplantation if surgery is anticipated in the next 2 years.
  • Left ventricular thrombus by echocardiography, MRI or left ventriculogram.
  • Peripheral artery disease that precludes cardiac catheterization with 8 Fr sheaths. .
  • Anterior wall thickness < 8 mm by echocardiography or MRI one month prior to enrollment.
  • Chronic renal failure (creatinine > 2,5 mg/dL).
  • I or IV NYHA functional class. Cardiogenic shock is defined as systolic blood pressure < 90 mmHg with no response to fluids, or < 100 mmHg with inotropes and without bradycardia.
  • Previous history of drug abuse (alcohol, etc…).
  • Acute or chronic infectious disease (including B/C hepatitis and HIV).
  • Pregnancy or child-bearing period.
  • MRI contraindications: pacemakers, ICD, metalic prosthesis, etc.
  • Bleeding or coagulation disorders (INR > 2 without anticoagulation treatment).
  • Cancer history 5 years prior to enrollment.
  • Life expectancy less than 1 year.
  • Any disease or condition that the investigator finds decisive for exclusion
  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: NCT01957826

Contacts
Contact: Ricardo Sanz, MD 034 91 426 5882 rsanzruiz@hotmail.com
Contact: Francisco Fernandez Avilés, MD

Locations
Spain
Hospital General Universitario Gregorio Marañón Recruiting
Madrid, Spain, 28007
Contact: Ricardo Sanz, MD    034 91 426 5882    rsanzruiz@hotmail.com   
Contact: • Francisco Fernandez Aviles, PhD         
Principal Investigator: Ricardo Sanz, MD         
Sub-Investigator: Francisco Fernández-Avilés, PhD         
Sub-Investigator: Pedro Luis Sánchez, MD         
Sub-Investigator: María Eugenia Fernández, PhD         
Sub-Investigator: Enrique Gutiérrez, MD         
Sub-Investigator: Esther Pérez, MD         
Sub-Investigator: Adolfo Villa, MD         
Sub-Investigator: Javier Anguita, MD         
Sub-Investigator: • Juan Carlos Alonso, MD         
Hospital Clinico Universitario de Valladolid Not yet recruiting
Valladolid, Spain
Principal Investigator: • José Alberto San Román, MD         
Sub-Investigator: Javier López         
Sub-Investigator: Pedro Mota         
Sub-Investigator: Roman Arnold         
Sponsors and Collaborators
Hospital General Universitario Gregorio Marañon
Ministerio de Sanidad, Servicios Sociales e Igualdad
Investigators
Study Chair: Francisco Fernandez Aviles, PhD Hospital General Universitario Gregorio Marañón
  More Information

No publications provided

Responsible Party: Hospital General Universitario Gregorio Marañon
ClinicalTrials.gov Identifier: NCT01957826     History of Changes
Other Study ID Numbers: FIBHGM-ECNC017-2010, 2010-024406-35, MIYOCYTE
Study First Received: December 21, 2012
Last Updated: October 7, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Hospital General Universitario Gregorio Marañon:
mesenchymal
stem cells
transendocardial injection
dilated idiopathic cardiomyopathy
idiopathic cardiomyopathy

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

ClinicalTrials.gov processed this record on July 24, 2014