Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced NK-mediated Rejection

NCT ID: NCT03955172

Last Updated: 2024-06-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-03

Study Completion Date

2027-12-03

Brief Summary

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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.

Detailed Description

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Conditions

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Kidney Transplant Failure and Rejection

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Everolimus

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

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).

Interventions

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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).

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Service de transplantation, néphrologie et immunologie clinique, Hôpital Edouard Herriot (HCL)

Lyon, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Alice KOENIG, MD

Role: CONTACT

472110178 ext. +33

Daniel SPERANDIO, MD

Role: CONTACT

472116926 ext. +33

Facility Contacts

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Alice KOENIG, MD

Role: primary

472110178 ext. +33

Daniel SPERANDIO

Role: backup

472116926 ext. +33

Other Identifiers

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69HCL17_0706

Identifier Type: -

Identifier Source: org_study_id

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