Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

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.

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.

Study Overview

• Status: Unknown
• Conditions: Primary Idiopathic Dilated Cardiomyopathy
• Intervention / Treatment: Other: placebo intervention; Other: bone marrow-derived MSCs injection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ricardo Sanz, MD; Phone Number: 034 91 426 5882; Email: rsanzruiz@hotmail.com
• Study Contact Backup: Name: Francisco Fernandez Avilés, MD

Study Locations

• Spain
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Maranon
    • Contact: Ricardo Sanz, MD; Phone Number: 034 91 426 5882; Email: 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
  • Valladolid, Spain
    • Not yet recruiting
    • Hospital Clínico Universitario de Valladolid
    • Principal Investigator: • José Alberto San Román, MD
    • Sub-Investigator: Javier López
    • Sub-Investigator: Pedro Mota
    • Sub-Investigator: Roman Arnold

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac adverse events. SAEs and AEs.	Major adverse cardiac adverse events includes cerebral adverse events	change from enrollment( 1, 3, 6, 12, 18 and 24 months)
NYHA functional class.		Change from enrolment( 1, 3, 6, 12, 18, 24 months)
Incidence of complications with the use of NOGA XPTM catheters.		Change from enrolment( 1, 3, 6, 12, 18, 24 months)
Laboratory parameters including C-reactive protein an brain natriuretic peptide		Change from enrolment( 1, 3, 6, 12, 18, 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NYHA Functional Class		1, 3, 6, 12, 18, 24 months
Max.oxygen consumption(MVO2),functional capacity.		6,12,24 months
Quality of life questionnaires	include 36-item Short Form Survey(SF 36) and Minnesota Living UIT Heart Failure questionnaire	6,12 and 24 months
Extension. of perfusion defects(MRI/SPECT).		6 and 24 months
LVEF, ventricular vol.,wall motion score index(echocard./MRI/SPECT		6,12 and 24 months
LVEF(left ventriculogram, electromech. mapping parameters(NOGA XPTM))		12 months

Collaborators and Investigators

• Sponsor: Hospital General Universitario Gregorio Marañon
• Collaborators: Ministerio de Sanidad, Servicios Sociales e Igualdad
• Investigators: Study Chair: Francisco Fernandez Aviles, PhD, Hospital General Universitario Gregorio Maranon

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: December 21, 2012
• First Submitted That Met QC Criteria: October 7, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Estimate): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: stem cells; mesenchymal; transendocardial injection; dilated idiopathic cardiomyopathy; idiopathic cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: FIBHGM-ECNC017-2010; 2010-024406-35 (EudraCT Number); MIYOCYTE (Other Identifier: MYOCYTE)