Cell-based Assays for Antibody-mediated Transplant Rejection

Sponsor

Plexision (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03916822

Collaborator

Medical University of South Carolina (Other)

Enrollment

Locations

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Goal: The goal of this study is to validate blood tests, which can detect antibody-mediated rejection (ABMR) after renal transplantation. These cell based assays measure CD154-expressing alloantigen-specific B-cells and their subsets in peripheral blood of adult renal transplant recipients. Thirty recipients will be enrolled at two transplant centers, 10 each with ABMR, T-cell mediated rejection (TCMR), and no rejection. Each subject will be sample twice, before and after rejection. Donor-specific anti-HLA antibodies will also be measured with single antigen beads.

Condition or Disease	Intervention/Treatment	Phase
Antibody-Mediated Graft Rejection	Diagnostic Test: Alloantigen-specific B-cells

Detailed Description

This cross-sectional open label study will evaluate whether alloantigen-specific B-cells and their subsets which express CD154 are associated with antibody-mediated rejection after first time renal transplantation in adult recipients.

Control groups include adult renal transplant recipients with T-cell-mediated rejection, and without rejection of any type.

Alloantigen-specific B-cells will be measured after stimulation of recipient peripheral blood leukocytes with those from corresponding donor and HLA-non-identical reference cells.

Thirty total subjects will be enrolled after IRB-approved informed consent, 15 at each of two sites. These subjects will include ten each with biopsy-proven ABMR and TCMR and ten with no rejection.

Each subject will be sampled twice, before and after treatment rejection, at intervals no less than 30 days, and not to exceed 90 days.

B-cells subsets will include those that also express cytokines, and those that are categorized as memory or naive, and their isotope switched or unswitched subsets, transitional B-cells or plasmablasts, etc.

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Validating Cell-based Assays for ABMR After Renal Transplantation

Actual Study Start Date :

Apr 15, 2019

Anticipated Primary Completion Date :

Jun 14, 2021

Anticipated Study Completion Date :

Aug 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
ABMR Biopsy-proven ABMR-Banff criteria, with or without Complement binding donor-specific anti-HLA antibodies	Diagnostic Test: Alloantigen-specific B-cells Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry
TCMR Biopsy-proven TCMR-Banff 1A, 1B, 2 and 3	Diagnostic Test: Alloantigen-specific B-cells Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry
No Rejection Biopsy-proven, or clinical criteria	Diagnostic Test: Alloantigen-specific B-cells Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry

Arm

Intervention/Treatment

ABMR

Biopsy-proven ABMR-Banff criteria, with or without Complement binding donor-specific anti-HLA antibodies

Diagnostic Test: Alloantigen-specific B-cells

Alloantigen-specific B-cells which express CD154 and their subsets which also co-express cytokines, memory and naive markers, and additional derivatives of these markers will be measured with flow cytometry

TCMR

Biopsy-proven TCMR-Banff 1A, 1B, 2 and 3

Diagnostic Test: Alloantigen-specific B-cells

No Rejection

Biopsy-proven, or clinical criteria

Diagnostic Test: Alloantigen-specific B-cells

Outcome Measures

Primary Outcome Measures

Antibody-mediated rejection [up to 90 days per subject]
Biopsy-proven antibody-mediated rejection after primary renal transplantation

Secondary Outcome Measures

T-cell mediated rejection (TCMR) [up to 90 days per subject]
Biopsy-proven TCMR after primary renal transplantation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

IRB-approved informed consent.
Adults (>18 yr to 70 years)
Primary renal transplant recipients with biopsy-proven ABMR, TCMR or recipients with no rejection