Transplantation of Human Embryonic Stem Cell-derived Progenitors in Severe Heart Failure (ESCORT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT02057900
First received: September 17, 2013
Last updated: October 5, 2015
Last verified: October 2015
  Purpose
The purpose of the study is to assess the feasibility and safety of a transplantation of cardiac-committed progenitor cells derived from human embryonic stem cells in patients with severe heart failure.

Condition Intervention Phase
Ischemic Heart Disease
Biological: Human embryonic stem cell-derived CD15+ Isl-1+ progenitors
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transplantation of Human Embryonic Stem Cell-derived CD15+ Isl-1+ Progenitors in Severe Heart Failure

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • number and nature of adverse events [ Time Frame: Within the first year after surgery ] [ Designated as safety issue: Yes ]
    Evidence for new clinical/biological abnormalities, occurrence of arrhythmias or development of a cardiac or extra-cardiac tumor.


Secondary Outcome Measures:
  • Feasibility of patch's generation and its efficacy on cardiac functions [ Time Frame: Within the first year after surgery ] [ Designated as safety issue: No ]
    Feasibility will be assessed by the ability to generate hESC-derived CD15+ Isl-1+ progenitors according to preset quality measures, to incorporate these cells in a fibrin patch, to deliver this patch onto the epicardium of the infarct area and to cover it with an autologous pericardial flap. Efficacy will be assessed on the following end points : 1- left ventricular function; 2- viability of the grafted area; 3- functional status; 4- major adverse cardiovascular events.


Estimated Enrollment: 6
Study Start Date: June 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Human embryonic stem cell
Patients with ischemic heart failure receiving a fibrin gel embedding human embryonic stem cell-derived CD15+ Isl-1+ progenitors in addition to coronary artery bypass grafting and/or a mitral valve procedure.
Biological: Human embryonic stem cell-derived CD15+ Isl-1+ progenitors
Epicardial delivery of a fibrin patch embedding human embryonic stem cell-derived CD15+ Isl-1+ progenitors

Detailed Description:
Heart failure due to coronary artery disease is a major problem because of its high prevalence, increased incidence and associated costs. When conventional medical/interventional treatments fail and if cardiac transplantation is contra-indicated, alternate options need to be considered. Transplantation of stem cells has emerged as one of them. While the optimal cell type still remains debatable, there is compelling evidence that cells whose phenotype closely matches that of the recipient tissue look sound candidates. In this context, human embryonic stem cells are attractive because of the possibility to drive their fate in vitro, prior to transplantation, towards a cardiac phenotype. We have developed a process for achieving such a commitment and generating cardiac-directed cells. The objective of this study is to assess both the feasibility and safety of this approach. In addition, the disadvantages of multiple intramyocardial injections have now been recognized. We have then taken advantage of the surgical setting of the trial (which entails concomitant coronary artery bypass or a mitral valve procedure) to switch from injections to the epicardial delivery of a fibrin gel into which the progenitor cells have been embedded. Coverage of this cell-loaded patch by an autologous pericardial flap is finally designed to provide trophic factors to the underlying cellular graft with the hope of improving its viability.
  Eligibility

Ages Eligible for Study:   18 Years to 81 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 and less than 81 years
  • Severe left ventricular systolic dysfunction with left ventricular ejection fraction (LVEF) ≤ 35% as assessed by echocardiography or scintigraphy
  • History of myocardial infarction (older than 6 months) with a residual akinesia involving more than 2 (out of 16) contiguous segments, as assessed by basal echocardiography
  • New York Heart Association (NYHA) Class III or IV despite optimal standard of care including diuretics and angiotensin receptor blockers and, if possible, beta blockers and aldosterone blockers
  • Previous implantation of an automatic internal defibrillator associated, whenever indicated, to ventricular resynchronization
  • Indication for a conventional cardiac surgical procedure : coronary artery bypass grafting involving, or not, the infarct area planned to be covered by the cell-loaded patch or mitral valve repair or replacement for ischemic mitral valve regurgitation; Non Eligibility to heart transplantation; Affiliation to a social security regimen
  • Willingness and ability to give written informed consent

Exclusion Criteria:

  • Pregnant or potentially child-bearing women
  • Patients with poor echogenicity
  • Left ventricular aneurysm
  • Contra-indication to immunosuppressive drugs (history of cancer, infections like B or C hepatitis, positivity for Hepatitis-B, HIV, HTLV1)
  • Contra-indication to sternotomy
  • Alloimmunisation against the cell line from which the progenitors are derived
  • Cardiogenic shock or NYHA Class IV heart failure requiring need for intravenous drugs
  • Intellectual deterioration or psychiatric disease interfering with the ability to obtain an informed consent and to achieve a close follow-up of the patient
  • Noncardiac disease which may reduce life expectancy in the short term
  • Simultaneous participation to another trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02057900

Contacts
Contact: Philippe Menasché, MD, PhD 33 1 56 09 20 00 ext 36 22 philippe.menasche@egp.aphp.fr
Contact: Albert A Hagège, MD, PhD 33 1 56 09 20 00 ext 37 13 albert.hagege@egp.aphp.fr

Locations
France
Department of Cardiovascular Surgery Recruiting
Paris, France, 75015
Contact: Philippe Menasché, MD, PhD    33 1 56 09 20 00 ext 36 22      
Contact: Albert A Hagège, MD, PhD    33 1 56 09 20 00 ext 37 13    albert.hagege@egp.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Philippe Menasché, MD, PhD Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Paris, France
  More Information

Publications:
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02057900     History of Changes
Other Study ID Numbers: P100303 
Study First Received: September 17, 2013
Last Updated: October 5, 2015
Health Authority: France: Committee for the Protection of Personnes

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Postinfarction heart failure
Transplantation of human embryonic stem cell-derived cardiac progenitors
Tissue-engineered cellular graft
Fibrin hydrogel

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Myocardial Ischemia
Coronary Artery Disease
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases

ClinicalTrials.gov processed this record on July 28, 2016