Assessment of T-cell Response and In-vitro Proof-of-concept of T-cell Engineering in Chronic ESKD Patients.

Recruiting

• Conditions: Chronic Kidney Diseases
• Interventions: Other: 1 blood sample for each participant

• Registration Number: NCT06474169
• Lead Sponsor: Centre Hospitalier Régional d'Orléans

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.

Study Timeline

• Study First Submitted: 2024-06-10
• Study First Submitted QC: 2024-06-19
• Study First Posted: 2024-06-25
• Study Start: 2024-11-27
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-17
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
n°2 (stage 3 CKD)	1 blood sample for each participant	stage 3 chronic kidney disease
n°3 (healthy donors)	1 blood sample for each participant	healthy donors
n°1 (ESKD)	1 blood sample for each participant	end-stage chronic kidney disease

Primary Outcome Measures

Name	Time	Method
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.	Duration of blood collection (approximately 5 minutes in inclusion)	Functional evaluation of T cells with specific viral assessment. Differents tests will be performed after peptidic stimulations: quantification of cytokines and proliferative capacities.

Secondary Outcome Measures

Name	Time	Method
in-vitro proof-of-concept of T-cell engineering	For each outcome, duration of blood collection (approximately 5 minutes in inclusion)	Development of mRNA delivery system to restore T-cell function in ESKD patients through T-cell therapy.

Trial Locations

Locations (1)

Center Hospitalier Universitaire d'Orléans; 🇫🇷 Orléans, France