Immune Response in Desensitized Patients

Kidney Transplant Rejection Clinical Trial

— DELIGHT  

Official title:

Impact of Desensitization Therapies on the Immune Response of Highly Sensitized Patients Awaiting Kidney Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05785936
• Other study ID #: 2022-A02445-38
• Status: Not yet recruiting
• Start date: May 1, 2023
• Est. completion date: April 30, 2025

Study information

• Verified date: March 2023
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Kidney transplantation is the best treatment for chronic renal failure in terms of morbidity and mortality, quality of life for patients and health economics. Sensitization with anti-Human Leukocyte Antigen antibodies is a barrier to access to transplantation.

Highly-sensitized patients wait 2 to 3 times longer on the waiting list with important health and economic consequences. Desensitization strategies by apheresis techniques allow access to a transplant with a negative crossmatch (absence of specific HLA antibodies against their donor) on the day of the transplant.

The main objective of this study is to assess the impact of desensitization on the antibody memory immune response in highly sensitized patients awaiting kidney transplantation.

The analyses will be based on samples from the 20 patients (10 desensitized transplanted patients, 5 highly sensitized non-desensitized transplanted patients and 5 healthy donors) at the University Hospital of Grenoble, France.

Analyses will include phenotypic and immuno-metabolic analysis by flow cytometry of antibody-secreting cells, a functional analysis by anti HLA ELISpot B technique and histological analysis of post-kidney transplantation follow-up renal biopsies with gene expression mapping (RNA tissue labeling using the Nanostring technique) within the renal parenchyma.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: April 30, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Adult patients (age >18 years) with end-stage renal disease (on hemodialysis or peritoneal dialysis or stage V chronic kidney disease) who are candidates for pre-renal transplantation desensitization from living or deceased donors.

• For women of childbearing age: a plasma pregnancy test before inclusion is mandatory. Highly effective contraception for women of childbearing age is required throughout the study period:

• combined hormonal contraception (containing estrogen and progestin)

• contraception associated with ovulation inhibition :

• oral

• intravaginal

• transdermal

• Progestin-only hormonal contraception associated with ovulation inhibition:

• oral

• injectable

• implantable

• intrauterine device (IUD) - intrauterine hormone delivery system (IUS)

• bilateral tubal occlusion

• vasectomized partner

• sexual abstinence

• Have signed the DELIGHT protocol consent.

• Affiliated to a social security system

• Can be contacted in case of emergency

• For the control groups :

• Healthy controls from blood samples (centrifugation ring) from the French Blood Agency. The use of healthy controls is necessary to compare immunological analyses to a reference group without immunosuppression.

• Highly sensitized kidney transplant patients without the need for de-immunization. Hyperimmunization is defined by a Panel Reactive Antibody score > 85%. Transplantation can be from deceased or living donors.

Exclusion Criteria:

• Patients who object to the use of their data and/or samples in the research

• Patients having received an immunosuppressive treatment in the 12 months preceding the inclusion

• All protected persons: pregnant women, parturients, nursing mothers, persons deprived of liberty by judicial or administrative decision, persons under legal protection.

• Subjects in a period of exclusion from another study

• Subject under administrative or judicial supervision

• Subject unable to be contacted in case of emergency

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Procedure:
• Desensitization
Patients that received apheresis and anti-cluster of differentiation antigen 20 for desensitization priori to kidney transplantation

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Flow Cytometry analyses of Peripheral Blood Mononuclear Cells	Change of the percentage of "antibody secreting cells" (plasmablasts) over time	Before desensitization, at the time of transplantation and Before desensitization, at the time of transplantation and post transplantation
Primary	Change in Anti HLA B-cell ELISpot response	Change in the number of Spot over time	Before desensitization, at the time of transplantation and Month 3, Month 6 and Month 12 post transplantation
Primary	Change in Flow Cytometry analyses of medullary cells	Change in the percentage of "antibody secreting cells" (plasmablasts) over time	The first day of desensitization and at the day of kidney transplantation
Primary	Change in analyses of RNA expression on renal histology	CHange in percentage of gene expression using Nanostring technology	Month1, Month 3 and Month 12 post transplantation