Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced NK-mediated Rejection
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An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Everolimus.
- Who it may be relevant to
- Registry conditions: Kidney Transplant Failure and Rejection. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced Natural Killer Cells Mediated (NK-mediated) Rejection
Overview
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.
Interventions
- Drug Everolimus
Patients will received everolimus (CERTICAN), oral form, at the necessary dose to obtain trough levels between 6 and 8 ng/ml, during 6 months. Everolimus will replace the anti-proliferative drug they have before (azathioprine or mycophenolic acid). Everolimus will be associated with corticosteroids (prednisolone) and a calcineurin inhibitor (tacrolimus or cyclosporin).
Primary outcome measures
- Change in Estimated glomerular filtration rate [Time frame: 6 months after start of Everolimus treatment]
Secondary outcome measures (3)
- Change in the severity of rejection lesions on allograft biopsy [Time frame: 6 months after start of Everolimus treatment]
- Change in NK cell activability [Time frame: 6 months after start of Everolimus treatment]
- Change in proteinuria [Time frame: 6 months after start of Everolimus treatment]
Eligibility criteria
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
Exclusion criteria
- Proteinuria/urinary creatinin > 100 mg/mmol
- Antecedent of poor tolerance or hypersensibility to everolimus or sirolimus
- Severe chronic lesions
- Presence of donor specific antibodies
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
France · 1 center
- Service de transplantation, néphrologie et immunologie clinique, Hôpital Edouard Herriot ( — Lyon
Identifiers
NCT: NCT03955172 · 69HCL17_0706