Ischemic Heart Disease
Conditions
Keywords
Postinfarction heart failure, Transplantation of human embryonic stem cell-derived cardiac progenitors, Tissue-engineered cellular graft, Fibrin hydrogel
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.
Interventions
BIOLOGICALHuman embryonic stem cell-derived CD15+ Isl-1+ progenitors
Epicardial delivery of a fibrin patch embedding human embryonic stem cell-derived CD15+ Isl-1+ progenitors
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 81 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| number and nature of adverse events | Within the first year after surgery | Evidence for new clinical/biological abnormalities, occurrence of arrhythmias or development of a cardiac or extra-cardiac tumor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of patch's generation and its efficacy on cardiac functions | Within the first year after surgery | 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. |
Countries
France
Outcome results
None listed