Kidney Transplant Failure and RejectionSTARRNCT03955172
Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced NK-mediated Rejection
A study testing Everolimus in people with Kidney Transplant Failure and Rejection, run by Hospices Civils de Lyon at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Kidney Transplant Failure and Rejection
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 3 Dec 2020to 3 Dec 2027
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Proteinuria/urinary creatinin > 100 mg/mmol
- Antecedent of poor tolerance or hypersensibility to everolimus or sirolimus
- Severe chronic lesions
- Presence of donor specific antibodies
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Service de transplantation, néphrologie et immunologie clinique, Hôpital Edouard Herriot (HCL)
Lyon, 69003
Alice KOENIG, MD, 472110178 ext. +33, alice.koenig@chu-lyon.fr
Daniel SPERANDIO, 472116926 ext. +33, daniel.sperandio@chu-lyon.fr
About this study
Official title: 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.
Read more
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
- Being tested
- Everolimus
- Keywords
- Missing self, NK cells, Rejection, mTOR inhibitors, Kidney transplanted patients
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Not described Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 months after start of Everolimus treatment
Secondary outcomes (3)
Change in the severity of rejection lesions on allograft biopsy
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).
Measured: 6 months after start of Everolimus treatment
Change in NK cell activability
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).
Measured: 6 months after start of Everolimus treatment
Change in proteinuria
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).
Measured: 6 months after start of Everolimus treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2019
- Study start3 Dec 2020
- Primary completion3 Dec 2027 (estimated)
- Study completion3 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Transplant Failure and RejectionStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03955172
- Sponsor's protocol ID
- 69HCL17_0706
- Acronym
- STARR
- Status last verified
- Oct 2026
- First submitted
- 16 May 2019
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No