Impact of ExtraCorporeal Phototherapy (ECP) on Auxiliary Follicular T-lymphocytes and Circulating B-lymphocytes During Chronic AntiBody-Mediated Rejection in Kidney Transplantation. (IPECAM)

Impact of ExtraCorporeal Phototherapy (ECP) on Auxiliary Follicular T-lymphocytes and Circulating B-lymphocytes During Chronic AntiBody-Mediated Rejection in Kidney Transplantation: IPECAM

Chronic AntiBody-Mediated Rejection (cABMR) is the leading cause of late kidney transplant loss (after 1 year of kidney transplantation). Its therapeutic management is poorly codified and there is currently no treatment referring.

Extracorporeal phototherapy (ECP) is a therapeutic apheresis that involves purifying mononucleated cells in the blood, exposing them to UltraViolet A (UVA) and re-injecting them to the patient. This treatment is used as common care in the first line as part of the treatment of cutaneous T lymphoma and in the second line as part of the graft versus host reaction after bone marrow allograft.

The mechanisms underlying the action of the ECP are not well known. They are mediated by the reinjection of cells exposed to UVA which enter apoptosis and induce immunomodulation. Recent work during cABMR shows that TFH lymphocytes, the maturing population of B lymphocytes, are deregulated and activated.

The hypothesis is that ECP can modulate T Follicular Helper (TFH) lymphocytes during cABMR.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplantation
• Intervention / Treatment: Other: Extracorporeal phototherapy

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emma BLANCHET; Phone Number: +33 2 41 35 63 38; Email: EmBlanchet@chu-angers.fr
• Study Contact Backup: Name: Jean-François AUGUSTO, Pr; Phone Number: +33 2 41 35 50 63; Email: JFAugusto@chu-angers.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• ECP treatment decision based on transplant team habits (care management)
• Age ≥ 18 years
• Affiliation to a French social security scheme
• Kidney transplant at least 6 months prior to inclusion

• cABMR proven by a renal graft biopsy less than 3 months and meeting the following histological criteria:

  • allograft glomerulopathy (cg>0, and maximum score cg2) or intimal fibrosis
  • C4d positive or ptc+g greater than or equal to 2
  • Presence of Donor Specific Antibody (DSA)
  • Interstitial Fibrosis and Tubular Atrophy (IFTA) less than or equal to 2
• Glomerular filtration rate > 30 mL/min/1.73 m2
• Signed informed consent to participate in the study

Exclusion Criteria:

• Active infection or infection with hepatitis B, C or HIV virus
• Pregnant, breastfeeding or parturient woman
• Person deprived of liberty by judicial or administrative decision
• Person receiving psychiatric care under duress
• Person subject to legal protection
• Person out of state to express consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extracorporeal phototherapy	Other: Extracorporeal phototherapy; The principle of ECP is to collect mononucleated cells from the blood by centrifugation. After purification, the mononucleated cells are incubated ex-vivo with a photo-activatable DNA intercalating agent (8-methoxypsoralen, UVADEX®), then re-injected to the patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of TFH cells and their activation markers	Variation in the frequency of TFH cells and their activation markers under treatment.	From the 1st session of ECP to 1 year after the 1st session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subsequent ECP response in patients with cABMR	Study of the 3-month TFH/TFR value of ECP treatment as a marker for subsequent ECP response in patients with cABMR	3 months of treatment per ECP
Concentration of pro and anti-inflammatory cytokines	Study of the concentration of pro-inflammatory cytokines (IL-6, TNFα, IL-1β, IL-17, IFN-gamma, IL-21, IL-12, IL-17, CXCL13) and anti-inflammatory cytokines (IL10, TGF-b) over time in ECP	From the 1st session of ECP to 1 year after the 1st session
Concentration of circulating B-cell populations	Study of the concentration of circulating B-cell populations due to ECP	From the 1st session of ECP to 1 year after the 1st session
Measurement of genetic markers in TFH cells	Study of genetic markers in TFH cells in cell co-culture in vitro to describe their function	At 1 week of the 1st session of ECP and at 3 month after the 1st session
Comparison of clinical data of patients	Clinical measures (medical examinations) of patients	From the 1st session of ECP to 1 year after the 1st session
Comparison of biological data of patients	Biological measures (blood samples) of patients	From the 1st session of ECP to 1 year after the 1st session

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Collaborators: Mallinckrodt

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Kidney Transplantation; Chronic AntiBody-Mediated Rejection; ExtraCorporeal Phototherapy
• Other Study ID Numbers: 2021-A00580-41

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No