Clinical trial NCT06474169: Assessment of T-cell Response and In-vitro Proof-of-concept of T-cell Engineering in Chronic ESKD Patients.
Official title: Assessment of T-cell Response and In-vitro Proof-of-concept of T-cell Engineering in Chronic End-stage Kidney Disease Patients.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Kidney Diseases
Keywords: end-stage kidney disease
T-cells response
Immunodeficiency
Proof of concept of T-cell therapy
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
First posted: 2024-06-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with chronic kidney disease followed in Nephrology department of Orléans University Hospital (CHU d'Orléans):

group 1 : end-stage kidney disease and group 2 : stage 3 chronic kidney disease

Healthy donors in Etablissement français du Sang (EFS) in Orleans:

Group 3 : healthy donors

Brief summary: This is a comparative, prospective, non-interventional study to evaluate immune response in patients with chronic kidney disease. The primary objective is to define immunodeficiency (phenotype and function of T cells) in patients with end-stage kidney disease. The second objective is to provide an in-vitro proof-of-concept of T-cell engineering in the context of end-stage kidney disease.

The study population was patients with chronic kidney disease.

Detailed description: The development of chronic kidney disease (CKD) and its progression to this terminal stage (end-stage kidney disease, ESKD) remains a significant source of reduced quality of life and premature mortality. ESKD represents the complete and definitive alteration of renal function requiring the use of renal replacement therapy (dialysis or kidney transplantation).

ESKD is associated with a significant increase in mortality, with a death rate of 10.9% and a median age of 77 years. Thus, the average survival of patients with ESKD is lower than that of the general population. Among the causes of death in ESKD, infectious diseases represent the 2nd cause of mortality and are responsible for 15 to 20% of deaths. The occurrence of complications increases with the decline of renal function, although individual risk remains poorly characterized. Thus, after infection, ESKD patients are at increased risk of complications, hospitalization, and death. This susceptibility to infections is explained by a complex alteration of the immune system, including a pro-inflammatory state and immunodeficiency. However, this immunodeficiency is still partially understood. Premature-aged T cells were found, with a decrease in naive T cells and an increase in memory T cells, suggesting a more advanced T-cell differentiation than in the population of the same age.

The study aims to describe immunodeficiency in patients with ESKD in order to better assess the infection risk for each patient, particularly in patients awaiting kidney transplantation.

This is a comparative, prospective, non-interventional study. Three groups of participants will be included: 1) patients with ESRK, 2) patients with stage 3 CKD, and 3) healthy donors. Participants will be included after being informed and after obtaining no opposition to participate. Immunodeficiency in patients with chronic kidney disease will be performed from a single blood sample.

A total of 100 participants will be included in this study based on the detection probability of naïve T cells (45% in patients with stage 3 CKD and healthy donors vs 10-15% in ESKD patients) and considered a power of 80% and an alpha risk of 5%.

The development of blood tests to evaluate the antiviral immune response could allow for the definition of new milestones for the development of future treatments or diagnostics for these diseases.

Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years
2. Informed participants who did not object to participating in the study

Exclusion Criteria:

1. Chronic progressive infections
2. Prior organ transplantation (including bone marrow transplantation)
3. Previous treatment with immunosuppressive agents (such as Rituximab, Eculizumab, Tacrolimus or Ciclosporin, Cellcept or Imurel) within 2 years prior to inclusion
4. Participant under guardianship, curatorship or deprived of liberty
5. Pregnant or breastfeeding women

Primary outcomes:
measure: The primary outcome is to characterize T cell immunodeficiency in our cohort of end-stage kidney disease patients from a phenotypic and functional point of view.
timeFrame: Duration of blood collection (approximately 5 minutes in inclusion)
measure: The primary outcome is to characterize T cell immunodeficiency in our cohort of end-stage kidney disease patients from a phenotypic and functional point of view.
timeFrame: Duration of blood collection (approximately 5 minutes in inclusion)
measure: The primary outcome is to characterize T cell immunodeficiency in our cohort of end-stage kidney disease patients from a phenotypic and functional point of view.
timeFrame: Duration of blood collection (approximately 5 minutes in inclusion)
Secondary outcomes:
measure: in-vitro proof-of-concept of T-cell engineering
timeFrame: For each outcome, duration of blood collection (approximately 5 minutes in inclusion)
Other outcomes:
Locations:
city: Orléans
country: France
facility: Center Hospitalier Universitaire d'Orléans
Study officials:
References:
citation: Ishigami J, Matsushita K. Clinical epidemiology of infectious disease among patients with chronic kidney disease. Clin Exp Nephrol. 2019 Apr;23(4):437-447. doi: 10.1007/s10157-018-1641-8. Epub 2018 Sep 3.
citation: Syed-Ahmed M, Narayanan M. Immune Dysfunction and Risk of Infection in Chronic Kidney Disease. Adv Chronic Kidney Dis. 2019 Jan;26(1):8-15. doi: 10.1053/j.ackd.2019.01.004.
citation: Betjes MG. Immune cell dysfunction and inflammation in end-stage renal disease. Nat Rev Nephrol. 2013 May;9(5):255-65. doi: 10.1038/nrneph.2013.44. Epub 2013 Mar 19.
citation: Betjes MG, Huisman M, Weimar W, Litjens NH. Expansion of cytolytic CD4+CD28- T cells in end-stage renal disease. Kidney Int. 2008 Sep;74(6):760-7. doi: 10.1038/ki.2008.301. Epub 2008 Jul 9.
citation: Betjes MG, Langerak AW, van der Spek A, de Wit EA, Litjens NH. Premature aging of circulating T cells in patients with end-stage renal disease. Kidney Int. 2011 Jul;80(2):208-17. doi: 10.1038/ki.2011.110. Epub 2011 Apr 27.
citation: Litjens NH, van Druningen CJ, Betjes MG. Progressive loss of renal function is associated with activation and depletion of naive T lymphocytes. Clin Immunol. 2006 Jan;118(1):83-91. doi: 10.1016/j.clim.2005.09.007. Epub 2005 Oct 27.
citation: Xiang F, Chen R, Cao X, Shen B, Chen X, Ding X, Zou J. Premature aging of circulating T cells predicts all-cause mortality in hemodialysis patients. BMC Nephrol. 2020 Jul 13;21(1):271. doi: 10.1186/s12882-020-01920-8.