Informations générales (source: ClinicalTrials.gov)
Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced Natural Killer Cells Mediated (NK-mediated) Rejection (STARR)
Interventional
N/A
Hospices Civils de Lyon (Voir sur ClinicalTrials)
décembre 2020
décembre 2027
29 juin 2024
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.
Etablissements
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Service de transplantation, néphrologie et immunologie clinique, Hôpital Edouard Herriot (HCL) - 69003 - Lyon - France | Alice KOENIG, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Patient aged > 18 years
- Kidney transplanted patient
- Having microvascular inflammation lesion on his graft biopsy associated to mild
chronic lesions
- In absence of donor specific antibodies
- In presence of a missing self
- Patient aged > 18 years
- Kidney transplanted patient
- Having microvascular inflammation lesion on his graft biopsy associated to mild
chronic lesions
- In absence of donor specific antibodies
- In presence of a missing self
- Proteinuria/urinary creatinin > 100 mg/mmol
- Antecedent of poor tolerance or hypersensibility to everolimus or sirolimus
- Severe chronic lesions
- Presence of donor specific antibodies