Ignite Creation Date:
2024-05-06 @ 1:10 PM
Last Modification Date:
2024-10-26 @ 1:10 PM
Study NCT ID:
NCT03955172
Status:
RECRUITING
Last Update Posted:
2024-06-06
First Post:
2019-05-16
Brief Title:
Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced NK-mediated Rejection
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
Official Title:
Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced Natural Killer Cells Mediated NK-mediated Rejection
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
STARR
Brief Summary:
Background
Long-term success of organ transplantation is limited by the inexorable loss of graft function due to rejection Prevalent dogma defends that allograft rejection is exclusively mediated by the adaptive immune system T cells are responsible for cellular rejections and B cells producing Donor Specific Antibodies DSA are responsible for humoral rejection Recently we demonstrated that innate NK cells could be implicated in the generation of chronic vascular rejections lesions by sensing the absence of expression of self Major Histocompatibility Complex MHC class I molecules missing self on graft endothelial cells with their Killer cell immunoglobulin-like KIR receptors Using human in vitro and murine in vivo models we also showed that Mammalian Target Of Rapamycin mTOR inhibitors could efficiently prevent this new kind of rejection
Objective
The aim of our project is therefore to test in a cohort of kidney transplanted patients the efficiency of mTOR inhibitors to treat this new kind of rejection
Methods
A cohort of 20 kidney transplant patients with a missing self on their graft responsible for a NK-mediated rejection will be established prospectively An mTOR inhibitor will be introduced in these patients for 6 months in association with a calcineurin inhibitor and corticosteroids Graft function histological lesions and NK activability will be monitored following this modification of treatment
Long-term success of organ transplantation is limited by the inexorable loss of graft function due to rejection Prevalent dogma defends that allograft rejection is exclusively mediated by the adaptive immune system T cells are responsible for cellular rejections and B cells producing Donor Specific Antibodies DSA are responsible for humoral rejection Recently we demonstrated that innate NK cells could be implicated in the generation of chronic vascular rejections lesions by sensing the absence of expression of self Major Histocompatibility Complex MHC class I molecules missing self on graft endothelial cells with their Killer cell immunoglobulin-like KIR receptors Using human in vitro and murine in vivo models we also showed that Mammalian Target Of Rapamycin mTOR inhibitors could efficiently prevent this new kind of rejection
Objective
The aim of our project is therefore to test in a cohort of kidney transplanted patients the efficiency of mTOR inhibitors to treat this new kind of rejection
Methods
A cohort of 20 kidney transplant patients with a missing self on their graft responsible for a NK-mediated rejection will be established prospectively An mTOR inhibitor will be introduced in these patients for 6 months in association with a calcineurin inhibitor and corticosteroids Graft function histological lesions and NK activability will be monitored following this modification of treatment
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None