Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

Primary Idiopathic Dilated Cardiomyopathy Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01957826
• Other study ID #: FIBHGM-ECNC017-2010
• Secondary ID: 2010-024406-35MI
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: December 21, 2012
• Last updated: November 17, 2016
• Start date: March 2013
• Est. completion date: March 2018

Study information

• Verified date: November 2016
• Source: Hospital General Universitario Gregorio Marañon
• Contact: Ricardo Sanz, MD
• Phone: 034 91 426 5882
• Email: rsanzruiz[@]hotmail.com
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Primary Idiopathic Dilated Cardiomyopathy

Intervention

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.
• placebo intervention
placebo administration

Locations

Country	Name	City	State
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Clinico Universitario de Valladolid	Valladolid

Sponsors (2)

Lead Sponsor	Collaborator
Hospital General Universitario Gregorio Marañon	Ministerio de Sanidad, Servicios Sociales e Igualdad

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Primary	NYHA functional class.		Change from enrolment( 1, 3, 6, 12, 18, 24 months)	Yes
Primary	Incidence of complications with the use of NOGA XPTM catheters.		Change from enrolment( 1, 3, 6, 12, 18, 24 months)	Yes
Primary	Laboratory parameters including C-reactive protein an brain natriuretic peptide		Change from enrolment( 1, 3, 6, 12, 18, 24 months)	Yes
Secondary	NYHA Functional Class		1, 3, 6, 12, 18, 24 months	No
Secondary	Max.oxygen consumption(MVO2),functional capacity.		6,12,24 months	No
Secondary	Quality of life questionnaires	include 36-item Short Form Survey(SF 36) and Minnesota Living UIT Heart Failure questionnaire	6,12 and 24 months	No
Secondary	Extension. of perfusion defects(MRI/SPECT).		6 and 24 months	No
Secondary	LVEF, ventricular vol.,wall motion score index(echocard./MRI/SPECT		6,12 and 24 months	No
Secondary	LVEF(left ventriculogram, electromech. mapping parameters(NOGA XPTM))		12 months	No