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

NCT03955172 | Recruiting

• 1 other identifier: 69HCL17_0706
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Transplant Failure and Rejection

Keywords

Missing self; NK cells; Rejection; mTOR inhibitors; Kidney transplanted patients

Outcome Measures

Primary Outcomes (1)

• Change in Estimated glomerular filtration rate

  Glomerular filtration rate will be estimated by Chronic Kidney Disease - Epidemiology CollaborationI (CKD-EP) equation. Outcome evaluation at 6 months after everolimus treatment introduction (at D0) compared to baseline (between 15 and 30 days before D0).

  6 months after start of Everolimus treatment

Secondary Outcomes (3)

• Change in the severity of rejection lesions on allograft biopsy

  6 months after start of Everolimus treatment

• Change in NK cell activability

  6 months after start of Everolimus treatment

• Change in proteinuria

  6 months after start of Everolimus treatment

Study Arms (1)

Everolimus

EXPERIMENTAL

Drug: Everolimus

Interventions

Everolimus 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).

Everolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Proteinuria/urinary creatinin \> 100 mg/mmol
• Antecedent of poor tolerance or hypersensibility to everolimus or sirolimus
• Severe chronic lesions
• Presence of donor specific antibodies

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

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

Lyon, 69003, France

RECRUITING

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Alice KOENIG, MD

CONTACT

472110178; alice.koenig@chu-lyon.fr

Daniel SPERANDIO, MD

CONTACT

472116926; daniel.sperandio@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 20, 2019
• Study Start: December 3, 2020
• Primary Completion (Estimated): December 3, 2027
• Study Completion (Estimated): December 3, 2027
• Last Updated: June 6, 2024

Record last verified: 2024-06

Locations

FR (1)