Anti-CMV Cellular Immunity Quantification Using an IGRA Test in Kidney Transplant récipients and Hemodialysis Patients, Comparison to Control Patients

Hemodialysis Clinical Trial

— Quantiferon  

Official title:

Quantification de l'immunité T Anti-CMV à l'Aide d'un Test IGRA Chez Des Patients greffés rénaux et Des Patients dialysés, Comparaison Avec Une Population de témoins

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03916497
• Other study ID #: 38RC19.002
• Secondary ID: 2019-A00101-56
• Status: Completed
• Start date: April 30, 2019
• Est. completion date: July 30, 2019

Study information

• Verified date: September 2020
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Evaluation of anti-CMV T cellular immunity using an IGRA test (Quantiferon-CMV test) in kidney transplant recipients and hemodialysis patients, comparison to control patients.

Description:

Cytomegalovirus (CMV) infection is a common opportunistic complication after kidney transplantation (KT). It has been associated with high morbidity and mortality in kidney transplant recipients (KTR). Its actual management is only based on the humoral immunity : the main risk factor for CMV infection after KT is the association of a seropositive donor and a seronegative recipient (so-called "D+/R- mismatch").

However several studies have highlighted the essential role of cellular immunity to control CMV infection. The Quantiferon-CMV (QF-CMV) is an IGRA test (Interferon Gamma Releasing Assay) which evaluates T CD8 lymphocytes production of Interferon Gamma (IFNy) exposed to CMV antigens. Some studies have shown the possible interest of the QF-CMV in predicting CMV infection after antiviral prophylaxis discontinuation or when CMV viremia is detected.

However some limits have been underlined. First its positivity threshold hasn't been approved in KTR. Hemodialysis patients (HP) called to receive a renal allograft also suffered from altered immunity. No study has directly compared the QF-CMV value in KTR, HP and control patients.

That's why we propose evaluating the expression of basal cellular immunity against CMV (far from any active infection) in KTR and HP using the QF-CMV and comparing it to control patients population (not suffering from kidney dysfunction or immunosuppression).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 30, 2019
• Est. primary completion date: July 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria :

• For all patients :

• to be seropositive for CMV

• to not be opposed to the study

• For kidney transplant recipients :

• to have received a kidney graft for over 1 year

• to have received an induction therapy at transplantation time by anti-lymphocytes antibodies and steroids

• to be currently receiving immunosuppressive therapy by calcineurins inhibitors (tacrolimus or cyclosporine), mycophenolic acid with or without steroids

• to not suffer from another cause of immunosuppression

• For hemodialysis patients :

• to be treated by hemodialysis for end stage renal disease

• without prior solid organ transplant history

• to not suffer from another cause of immunosuppression

• For control patients :

• with normal kidney function (estimated GFR > 90 ml/min)

• to not suffer from another cause of immunosuppression

Exclusion Criteria :

• patient under guardianship or deprived of his liberty

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• Hemodialysis
• Infection
• Kidney Transplant Infection
• Quantiferon-CMV

Intervention

Diagnostic Test:
• Quantiferon CMV
Evaluate and compare interferon gamma (IFNy) production by T CD8 cells exposed to CMV antigens in CMV seropositive kidney transplant recipients, hemodialysis and control patients

Locations

Country	Name	City	State
France	Chu Grenoble Alpes	Grenoble

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (6)

Cantisán S, Lara R, Montejo M, Redel J, Rodríguez-Benot A, Gutiérrez-Aroca J, González-Padilla M, Bueno L, Rivero A, Solana R, Torre-Cisneros J. Pretransplant interferon-? secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation. Am J Transplant. 2013 Mar;13(3):738-45. doi: 10.1111/ajt.12049. Epub 2013 Jan 11. — View Citation

Kumar D, Chernenko S, Moussa G, Cobos I, Manuel O, Preiksaitis J, Venkataraman S, Humar A. Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients. Am J Transplant. 2009 May;9(5):1214-22. doi: 10.1111/j.1600-6143.2009.02618.x. — View Citation

Lisboa LF, Kumar D, Wilson LE, Humar A. Clinical utility of cytomegalovirus cell-mediated immunity in transplant recipients with cytomegalovirus viremia. Transplantation. 2012 Jan 27;93(2):195-200. doi: 10.1097/TP.0b013e31823c1cd4. — View Citation

Manuel O, Husain S, Kumar D, Zayas C, Mawhorter S, Levi ME, Kalpoe J, Lisboa L, Ely L, Kaul DR, Schwartz BS, Morris MI, Ison MG, Yen-Lieberman B, Sebastian A, Assi M, Humar A. Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study. Clin Infect Dis. 2013 Mar;56(6):817-24. doi: 10.1093/cid/cis993. Epub 2012 Nov 29. — View Citation

Radha R, Jordan S, Puliyanda D, Bunnapradist S, Petrosyan A, Amet N, Toyoda M. Cellular immune responses to cytomegalovirus in renal transplant recipients. Am J Transplant. 2005 Jan;5(1):110-7. — View Citation

Walker S, Fazou C, Crough T, Holdsworth R, Kiely P, Veale M, Bell S, Gailbraith A, McNeil K, Jones S, Khanna R. Ex vivo monitoring of human cytomegalovirus-specific CD8+ T-cell responses using QuantiFERON-CMV. Transpl Infect Dis. 2007 Jun;9(2):165-70. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantification of anti-CMV T cellular immunity in kidney transplant recipients, hemodialysis patients and control patients.	Quantification of IFNy level producted by T cells exposed to CMV antigens using a Quantiferon-CMV test in kidney transplant recipients, hemodialysis patients and control patients.	Single measurement at Day 0 of patient inclusion
Secondary	Quantification of patient cellular immunity.	Quantification of lymphocytes subpopulations.	Single measurement at Day 0 of patient inclusion
Secondary	Evaluation of kidney transplant recipient exposure to immunosuppressive therapy.	Assessment of last tacrolimus trough concentration.	Single collection at Day 0 of patient inclusion
Secondary	Estimation of renal function.	Evaluation of estimated glomerular filtration rate by plasmatic creatinin dosage using CKD-EPI estimate.	Single measurement at Day 0 of patient inclusion
Secondary	Assessment of CMV donor humoral immunity in kidney transplant recipients.	Assessment of donor CMV serology.	Single collection at Day 0 of patient inclusion