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

June 5, 2024 updated by: Hospices Civils de Lyon

Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced Natural Killer Cells Mediated (NK-mediated) Rejection

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Lyon, France, 69003
        • Recruiting
        • Service de transplantation, néphrologie et immunologie clinique, Hôpital Edouard Herriot (HCL)
        • Contact:
        • Contact:
        • Principal Investigator:
          • Alice KOENIG, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Everolimus
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Estimated glomerular filtration rate
Time Frame: 6 months after start of Everolimus treatment

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the severity of rejection lesions on allograft biopsy
Time Frame: 6 months after start of Everolimus treatment

Evolution of microvascular inflammation and chronic glomerular and vascular lesions graded according to Banff 2013 classification.

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
Change in NK cell activability
Time Frame: 6 months after start of Everolimus treatment

Nk cell activability will be measured by looking at the expression of activation markers (CD107a and MIP1B) on circulating NK cells by flow cytometry.

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
Change in proteinuria
Time Frame: 6 months after start of Everolimus treatment
Calculation of proteinuria/urinary creatinin index. 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 3, 2020

Primary Completion (Estimated)

December 3, 2027

Study Completion (Estimated)

December 3, 2027

Study Registration Dates

First Submitted

May 16, 2019

First Submitted That Met QC Criteria

May 16, 2019

First Posted (Actual)

May 20, 2019

Study Record Updates

Last Update Posted (Actual)

June 6, 2024

Last Update Submitted That Met QC Criteria

June 5, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL17_0706

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Kidney Transplant Failure and Rejection

Clinical Trials on Everolimus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Senegal

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe