B Cell Lymphocyte in Humoral Rejection and Alloimmunisation

Renal Transplant Clinical Trial

— BHL  

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03016455
• Other study ID #: BHL (RB 12.047)
• Status: Recruiting
• Phase: N/A
• First received: August 30, 2016
• Last updated: May 2, 2017
• Start date: June 2013
• Est. completion date: December 2017

Study information

• Verified date: April 2017
• Source: University Hospital, Brest
• Contact: Yannick LE MEUR, MD PhD
• Email: yannick.lemeur[@]chu-brest.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to better characterise B cell phenotype and functional abnormalities in kidney transplant patients producing donor specific antibody (DSA) and in those with chronic antibody mediated rejection (cAMR) and to search for a predictive tool (biomarker). The functional analysis will help to better understand B cell-dependant mechanisms implied in T cell proliferation and better target future treatments.

Description:

The principal objective is to better understand the B cell dependant mechanisms of the chronic antibody mediated rejection (cAMR). A particular focus will be done on the mechanisms that could explain the natural history of chronic humoral mediated rejection and of pathways from DSA negative status toward DSA positive status and from DSA positive status to histological lesions. The following will be undergone for three categories of patients (stable patients, DSA positive patients without cAMR and DSA positive patients with cAMR) :

• A phenotypic analysis of B cells of patients suffering from chronic humoral rejection or who are simply DSA positive.

• A functional analysis in autologous cultures in order to confirm our preliminary results.

• A functional analysis in a heterologous proliferation test aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR.

• A cytokine analysis (IL10, alpha-tumor necrosis factor, gamma-interferon dosing), for a better understanding of the mechanisms that are involved in the regulation of the T cell response that is induced by the B cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Non stable patients :

• Patient older than 18 years old.

• Patient which is the recipient of a renal transplant

• Patient who develops anti donor antibodies after the transplantation and / or suffering from a histologically-proven antibody mediated rejection.

• Patient who has signed an informed consent form

• Stable patients :

• Patient older than 18 years old.

• Patient that is the recipient of a renal transplant for more than one year

• Patient who has accepted to participate in the Brest Kidney graft recipient collection

• Patient that is not suffering from any rejection, that has a good renal function and a low proteinuria

• Patient that has not developed any DSA.

Exclusion criteria :

• Patients that has not signed the consent form.

Related Conditions & MeSH terms

• Renal Transplant

Intervention

Other:
• Presence of DSA w/ cAMR

• Presence of DSA w/o cAMR

• No DSA No cAMR

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	Chu Angers	Angers
France	CHU Brest	Brest
France	CHU CAEN	Caen
France	Chu Clermont Ferrand	Clermont Ferrand
France	CHU Limoges	Limoges
France	APHP Hôpital Necker	Paris
France	CHU Poitiers	Poitiers
France	CHU Reims	Reims
France	CHU Rennes	Rennes
France	CHU Rouen	Rouen
France	Hôpitaux Universitaires de Strasbourg	Strasbourg
France	CHU Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the ratio (percentage and absolute values) of mature LB subpopulations (LBm1 to LBm5) and of memory LB by specific labellings		At the inclusion day
Primary	Evaluation of the proliferation of freshly isolated cells T in presence of autologous B cells		At the inclusion day
Primary	Evaluation of the proliferation of T cells in a heterologous test	aiming at a better understanding of the absence of B cell regulation of T cell proliferation in patients suffering from cAMR	At the inclusion day
Primary	cytokine analysis(IL10, alpha-Tumor Necrosis FActor, gamma-Interferon dosing)	for a better understanding of the mechanisms that are involved in the regulation of the T cell response that is induced by the B cells.	At the inclusion day
Secondary	Correlation between phenotypic and functional evaluations, and clinical outcome		One year post inclusion
Secondary	comparison of the B cell subpopulations before and after rituximab treatment	In a subgroup of patients, the ones that will happen to be treated by rituximab for a rejection episode.	One year post inclusion