Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

NCT ID: NCT01957826

Last Updated: 2016-11-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2018-03-31

Brief Summary

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.

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.

Conditions

Primary Idiopathic Dilated Cardiomyopathy

Keywords

mesenchymal; stem cells; transendocardial injection; dilated idiopathic cardiomyopathy; idiopathic cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

placebo comparator

transendocardial injection of placebo solution

Group Type: PLACEBO_COMPARATOR

placebo intervention

Intervention Type: OTHER

placebo administration

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.

Group Type: EXPERIMENTAL

bone marrow-derived MSCs injection

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: OTHER

placebo intervention

placebo administration

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministerio de Sanidad, Servicios Sociales e Igualdad

OTHER_GOV

Sponsor Role: collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francisco Fernandez Aviles, PhD

Role: STUDY_CHAIR

Hospital General Universitario Gregorio Marañón

Locations

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, Spain

Site Status: RECRUITING

Hospital Clinico Universitario de Valladolid

Valladolid, Valladolid, Spain

Site Status: NOT_YET_RECRUITING

Countries

Spain

Central Contacts

Ricardo Sanz, MD

Role: CONTACT

Phone: 034 91 426 5882

Email: rsanzruiz@hotmail.com

Francisco Fernandez Avilés, MD

Role: CONTACT

Facility Contacts

Ricardo Sanz, MD

Role: primary

• Francisco Fernandez Aviles, PhD

Role: backup

Other Identifiers

2010-024406-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MIYOCYTE

Identifier Type: OTHER

Identifier Source: secondary_id

FIBHGM-ECNC017-2010

Identifier Type: -

Identifier Source: org_study_id