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

Kidney Transplantation Clinical Trial

— IPECAM  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04870437
• Other study ID #: 2021-A00580-41
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2021
• Est. completion date: June 1, 2023

Study information

• Verified date: April 2021
• Source: University Hospital, Angers
• Contact: Jean-François AUGUSTO, Pr
• Phone: +33 2 41 35 50 63
• Email: JFAugusto[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 1, 2023
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Angers	Mallinckrodt

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Concentration of pro and anti-inflammatory cytokines	Study of the concentration of pro-inflammatory cytokines (IL-6, TNFa, IL-1ß, 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
Secondary	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
Secondary	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
Secondary	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
Secondary	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