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Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

Primary Purpose

Primary Idiopathic Dilated Cardiomyopathy

Status

Unknown status

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

bone marrow-derived MSCs injection

placebo intervention

About this trial

This is an interventional treatment trial for Primary Idiopathic Dilated Cardiomyopathy focused on measuring mesenchymal, stem cells, transendocardial injection, dilated idiopathic cardiomyopathy, idiopathic cardiomyopathy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hospital General Universitario Gregorio MarañónRecruiting
Hospital Clinico Universitario de Valladolid

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

placebo comparator

bone marrow-derived MSCs injection

Arm Description

transendocardial injection of placebo solution

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.

Outcomes

Primary Outcome Measures

Major adverse cardiac adverse events. SAEs and AEs.

Major adverse cardiac adverse events includes cerebral adverse events

NYHA functional class.

Incidence of complications with the use of NOGA XPTM catheters.

Laboratory parameters including C-reactive protein an brain natriuretic peptide

Secondary Outcome Measures

NYHA Functional Class

Max.oxygen consumption(MVO2),functional capacity.

Quality of life questionnaires

include 36-item Short Form Survey(SF 36) and Minnesota Living UIT Heart Failure questionnaire

Extension. of perfusion defects(MRI/SPECT).

LVEF, ventricular vol.,wall motion score index(echocard./MRI/SPECT

LVEF(left ventriculogram, electromech. mapping parameters(NOGA XPTM))

Full Information

NCT ID

NCT01957826

First Posted

December 21, 2012

Last Updated

November 17, 2016

Sponsor

Hospital General Universitario Gregorio Marañon

Collaborators

Ministerio de Sanidad, Servicios Sociales e Igualdad

1. Study Identification

Unique Protocol Identification Number

NCT01957826

Brief Title

Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

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.

Study Type

Interventional

2. Study Status

Record Verification Date

November 2016

Overall Recruitment Status

Unknown status

Study Start Date

March 2013 (undefined)

Primary Completion Date

March 2018 (Anticipated)

Study Completion Date

March 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospital General Universitario Gregorio Marañon

Collaborators

Ministerio de Sanidad, Servicios Sociales e Igualdad

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Idiopathic Dilated Cardiomyopathy

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

placebo comparator

Arm Type

Placebo Comparator

Arm Description

transendocardial injection of placebo solution

Arm Title

bone marrow-derived MSCs injection

Arm Type

Experimental

Arm Description

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

Intervention Name(s)

bone marrow-derived MSCs injection

Intervention Description

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

Intervention Name(s)

placebo intervention

Intervention Description

placebo administration

Primary Outcome Measure Information:

Title

Major adverse cardiac adverse events. SAEs and AEs.

Description

Major adverse cardiac adverse events includes cerebral adverse events

Time Frame

change from enrollment( 1, 3, 6, 12, 18 and 24 months)

Title

NYHA functional class.

Time Frame

Change from enrolment( 1, 3, 6, 12, 18, 24 months)

Title

Incidence of complications with the use of NOGA XPTM catheters.

Time Frame

Change from enrolment( 1, 3, 6, 12, 18, 24 months)

Title

Laboratory parameters including C-reactive protein an brain natriuretic peptide

Time Frame

Change from enrolment( 1, 3, 6, 12, 18, 24 months)

Secondary Outcome Measure Information:

Title

NYHA Functional Class

Time Frame

1, 3, 6, 12, 18, 24 months

Title

Max.oxygen consumption(MVO2),functional capacity.

Time Frame

6,12,24 months

Title

Quality of life questionnaires

Description

include 36-item Short Form Survey(SF 36) and Minnesota Living UIT Heart Failure questionnaire

Time Frame

6,12 and 24 months

Title

Extension. of perfusion defects(MRI/SPECT).

Time Frame

6 and 24 months

Title

LVEF, ventricular vol.,wall motion score index(echocard./MRI/SPECT

Time Frame

6,12 and 24 months

Title

LVEF(left ventriculogram, electromech. mapping parameters(NOGA XPTM))

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ricardo Sanz, MD

Phone

034 91 426 5882

rsanzruiz@hotmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Francisco Fernandez Avilés, MD

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Francisco Fernandez Aviles, PhD

Organizational Affiliation

Hospital General Universitario Gregorio Marañón

Official's Role

Study Chair

Facility Information:

Facility Name

Hospital General Universitario Gregorio Marañón

City

Madrid

ZIP/Postal Code

28007

Country

Spain

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ricardo Sanz, MD

Phone

034 91 426 5882

rsanzruiz@hotmail.com

First Name & Middle Initial & Last Name & Degree

• Francisco Fernandez Aviles, PhD

First Name & Middle Initial & Last Name & Degree

Ricardo Sanz, MD

First Name & Middle Initial & Last Name & Degree

Francisco Fernández-Avilés, PhD

First Name & Middle Initial & Last Name & Degree

Pedro Luis Sánchez, MD

First Name & Middle Initial & Last Name & Degree

María Eugenia Fernández, PhD

First Name & Middle Initial & Last Name & Degree

Enrique Gutiérrez, MD

First Name & Middle Initial & Last Name & Degree

Esther Pérez, MD

First Name & Middle Initial & Last Name & Degree

Adolfo Villa, MD

First Name & Middle Initial & Last Name & Degree

Javier Anguita, MD

First Name & Middle Initial & Last Name & Degree

• Juan Carlos Alonso, MD

Facility Name

Hospital Clinico Universitario de Valladolid

City

Valladolid

Country

Spain

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

• José Alberto San Román, MD

First Name & Middle Initial & Last Name & Degree

Javier López

First Name & Middle Initial & Last Name & Degree

Pedro Mota

First Name & Middle Initial & Last Name & Degree

Roman Arnold

12. IPD Sharing Statement

Learn more about this trial

Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

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