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

NCT ID: NCT02057900

Last Updated: 2018-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-27
• Study Completion Date: 2018-03-22

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.

Conditions

Ischemic Heart Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 81 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe Menasché, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Department of Cardiovascular Surgery

Paris, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 18841094 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29389360 (View on PubMed)

Other Identifiers

P100303

Identifier Type: -

Identifier Source: org_study_id