Orientation of the Lymphocyte Response to the Occurrence of Atherosclerotic Complications After Kidney Transplantation (ORLY-Est)

Influence de l'ORientation de la réponse LYmphocytaire Sur la Survenue de Complications athéromateuses après Transplantation rénale (étude ORLY-EST 2)

The incidence of atherosclerotic complications is increased after kidney transplantation. Traditional risk factors do not fully explain this increased risk. Atherosclerosis is an inflammatory disease in which all players in the immune response are involved. The impact of these immune responses is not well known in immunocompromised patients, particularly among organ transplant. Nevertheless, the work of our group suggest that innate and acquired responses through different mechanisms influencing the evolution of atheromatous disease after transplantation.

The investigators therefore propose to study the impact of the expansion of regulatory T cells on the risk of atherosclerotic complications after transplantation.

Since November 2008, the investigators began a multicenter, prospective study whose purpose is to study in detail the immunological mechanisms of atherosclerosis after transplantation via immunomonitoring cohort of renal transplant patients in the Grand East Interregion. It was planned to include 500 patients and to date a little more than half have been included. After completion of the blood test, the tubes are routed over the Biomonitoring Platform (CIC-BT 506 Besançon) and the samples are stored in CRB Dijon.

The atherosclerotic events are recorded prospectively. The investigators hope to implement as part of ORLY IS, a second study to determine the impact of an expansion of regulatory T cells on the risk of atherosclerotic events.

Our hypothesis is that a cell rate regulatory T below the median results in an increase of 5% of atherosclerotic complications.

Study Overview

• Status: Active, not recruiting
• Conditions: Disorder Related to Renal Transplantation
• Intervention / Treatment: Other: blood sample

• Study Type: Observational
• Enrollment (Actual): 1150

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25000
    • CHU de Besancon
  • Clermont-Ferrand, France, 63003
    • CHU Clermont-Ferrand, 58 rue Montalembert, 63003 Clermont-Ferrand
  • Dijon, France, 21079
    • CHU Dijon, Hôpital du Bocage, 2 Bd du Maréchal de Lattre de Tassigny, 21079 Dijon cedex
  • Le Kremlin-Bicêtre, France, 94275
    • Hôpital du Kremlin Bicêtre 78, rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex
  • Nancy, France
    • CHU Brabois, et Vandoeuvre les Nancy
  • Reims, France, 51092
    • CHU Reims, 45 rue Cognacq-Jay 51092 Reims Cedex
  • Strasbourg, France, 67091
    • Hôpital Civil- 1, place de l'hôpital BP426 ; 67091 Strasbourg Cedex

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population corresponds to 1000 patients receiving a renal transplant in Hospital of Besançon, Dijon, Nancy, Reims, Clermont-Ferrand, Strasbourg et Kremlin-Bicêtre.

Description

Inclusion Criteria:

1. Male or female patients aged over 18 years
2. Patients receiving a renal transplant
3. Patients able to understand the benefits and risks of testing
4. Patients gave written informed consent.

Exclusion Criteria:

1. Inability to understand the advantages and disadvantages of the study; psychiatric disorders judged by the investigator to be incompatible with the inclusion in the study.
2. Immunosuppressive therapy immediately prior to transplantation
3. Cancer (except skin cancer) or malignant blood disease being treated; active infection; decompensated cirrhosis [patients had cancer and considered as cured or in remission, patients with virus infection of hepatitis B or hepatitis C and having no cirrhosis may be included].

This study is strictly non-interventional, participation in another study is not a cons-indication to the inclusion in this study and no exclusion period is required for inclusion in another study after inclusion in this study (Art L. 1121-12 (loi n°2004-806 du 9 Août 2004).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of regulatory T cells related to atherosclerotic complications events.	Percentage of regulatory T cells	5 or 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atherosclerotic complications events	Percentage of regulatory T cells	5 or 10 years
Genetic determinants (TNF-alpha, IL-6,...) related to cardiovascular events	Percentage of regulatory T cells	5 or 10 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon
• Collaborators: Etablissement Français du Sang; University of Franche-Comté
• Investigators: Principal Investigator: Didier Ducloux, Pr., CHRU De Besancon

Publications and helpful links

General Publications

• Ducloux D, Courivaud C, Bamoulid J, Crepin T, Gaiffe E, Laheurte C, Vauchy C, Rebibou JM, Saas P, Borot S. Immune phenotype predicts new onset diabetes after kidney transplantation. Hum Immunol. 2019 Nov;80(11):937-942. doi: 10.1016/j.humimm.2019.08.006. Epub 2019 Sep 10.
• Ducloux D, Legendre M, Bamoulid J, Rebibou JM, Saas P, Courivaud C, Crepin T. ESRD-associated immune phenotype depends on dialysis modality and iron status: clinical implications. Immun Ageing. 2018 Jul 17;15:16. doi: 10.1186/s12979-018-0121-z. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2008
• Primary Completion (Actual): October 23, 2020
• Study Completion (Anticipated): October 23, 2030

Study Registration Dates

• First Submitted: July 8, 2016
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (Estimate): July 26, 2016

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Immunology; Atherosclerosis; Transplantation
• Other Study ID Numbers: R/2011/44

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Identified individual participant data for all outcome measures will be made available within 6 monts of study completion