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

Primary Purpose

Ischemic Heart Disease

Status

Completed

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

Human embryonic stem cell-derived CD15+ Isl-1+ progenitors

About this trial

This is an interventional treatment trial for Ischemic Heart Disease focused on measuring Postinfarction heart failure, Transplantation of human embryonic stem cell-derived cardiac progenitors, Tissue-engineered cellular graft, Fibrin hydrogel

Eligibility Criteria

18 Years - 81 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Department of Cardiovascular Surgery

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Human embryonic stem cell

Arm Description

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.

Outcomes

Primary Outcome Measures

number and nature of adverse events

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

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.

Full Information

NCT ID

NCT02057900

First Posted

September 17, 2013

Last Updated

July 9, 2018

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT02057900

Brief Title

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

Acronym

ESCORT

Official Title

Transplantation of Human Embryonic Stem Cell-derived CD15+ Isl-1+ Progenitors in Severe Heart Failure

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

May 27, 2013 (Actual)

Primary Completion Date

March 22, 2018 (Actual)

Study Completion Date

March 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

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

Ischemic Heart Disease

Keywords

Postinfarction heart failure, Transplantation of human embryonic stem cell-derived cardiac progenitors, Tissue-engineered cellular graft, Fibrin hydrogel

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Human embryonic stem cell

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Human embryonic stem cell-derived CD15+ Isl-1+ progenitors

Intervention Description

Epicardial delivery of a fibrin patch embedding human embryonic stem cell-derived CD15+ Isl-1+ progenitors

Primary Outcome Measure Information:

Title

number and nature of adverse events

Description

Evidence for new clinical/biological abnormalities, occurrence of arrhythmias or development of a cardiac or extra-cardiac tumor.

Time Frame

Within the first year after surgery

Secondary Outcome Measure Information:

Title

Feasibility of patch's generation and its efficacy on cardiac functions

Description

Time Frame

Within the first year after surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

81 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Philippe Menasché, MD, PhD

Organizational Affiliation

Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Paris, France

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department of Cardiovascular Surgery

City

Paris

ZIP/Postal Code

75015

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

18841094

Citation

Puymirat E, Geha R, Tomescot A, Bellamy V, Larghero J, Trinquart L, Bruneval P, Desnos M, Hagege A, Puceat M, Menasche P. Can mesenchymal stem cells induce tolerance to cotransplanted human embryonic stem cells? Mol Ther. 2009 Jan;17(1):176-82. doi: 10.1038/mt.2008.208. Epub 2008 Oct 7.

Results Reference

result

PubMed Identifier

29389360

Citation

Menasche P, Vanneaux V, Hagege A, Bel A, Cholley B, Parouchev A, Cacciapuoti I, Al-Daccak R, Benhamouda N, Blons H, Agbulut O, Tosca L, Trouvin JH, Fabreguettes JR, Bellamy V, Charron D, Tartour E, Tachdjian G, Desnos M, Larghero J. Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitors for Severe Ischemic Left Ventricular Dysfunction. J Am Coll Cardiol. 2018 Jan 30;71(4):429-438. doi: 10.1016/j.jacc.2017.11.047.

Results Reference

derived

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

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