Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy

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.

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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Major adverse cardiac adverse events. SAEs and AEs.

Secondary Outcome

 NYHA Functional Class

Condition

Primary Idiopathic Dilated Cardiomyopathy

Intervention

bone marrow-derived MSCs injection

Study Arms / Comparison Groups

 placebo comparator

Description:  transendocardial injection of placebo solution

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Other

Estimated Enrollment

70

Start Date

March 2013

Completion Date

March 2018

Primary Completion Date

March 2018

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
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Francisco Fernandez Aviles, PhD, 034 91 426 5882, [email protected]

Location Countries

Spain

Location Countries

Spain

NCT ID

NCT01957826

Organization ID

FIBHGM-ECNC017-2010

Secondary IDs

2010-024406-35

Responsible Party

Sponsor

Study Sponsor

Hospital General Universitario Gregorio Marañon

Collaborators

 Ministerio de Sanidad, Servicios Sociales e Igualdad

Study Sponsor

Francisco Fernandez Aviles, PhD, Study Chair, Hospital General Universitario Gregorio Marañón

Verification Date

November 2016