A pilot clinical trial to evaluate the feasibility and acceptability of: A prospective, unblinded, randomized-controlled, multicenter biomarker intervention trial of a urinary CXCL10 clinical surveillance program in pediatric kidney transplant recipients for early ascertainment and treatment of subclinical allograft inflammation and preservation of kidney transplant function

Project Summary

Kidney transplant rejection remains a major issue for children after kidney transplantation. Rejection episodes are the primary contributor to premature kidney graft failure. Doctors prescribe medications known as immunosuppressants to prevent this form of immune system attack. Too much can sometimes increase side effects or infections. But too little risks kidney rejection. The right amount of immunosuppressants is different for everyone.

Current clinical monitoring with blood tests like serum creatinine are ineffective to identify early rejection. We have developed and validated a urine test called CXCL10 that effectively identifies inflammation within the transplant. CXCL10 is a small protein that is produced by your body's immune system when there is inflammation. When inflammation in the kidney is caused by early rejection, higher levels of CXCL10 can be found in the urine. Elevated urine CXCL10 levels may also indicate kidney infections.

This clinical trial will evaluate whether regular screening with CXCL10 can improve long-term graft function by effectively identifying and treating episodes graft inflammation at an early stage, before there is any detectable clinical impact from kidney damage. This study will randomize children who are more than six months after their kidney transplant to either receive the intervention of serial monitoring by urinary CXCL10, or will have samples collected as part of a control group. They will be followed for two years, to observe changes in kidney function in that time. The group that is assigned to do serial monitoring will have additional testing if the CXCL10 level is high, and will receive treatment based on the additional testing which includes diagnosis of rejection.

This first stage of the trial is to conduct a pilot study that will demonstrate the feasibility of the larger clinical trial. The goals will be to the establish that 1) we can meet a target to enroll and randomize 60 patients from 3 centers to the study; 2) we can execute the logistical aspects of the trial including obtaining samples on time, CXCL10 testing and reporting, and application of the protocol for positive CXCL10 tests; and 3) to determine the most economical approach for testing in the larger trial. The findings of this trial will be used to support a subsequent application for a larger, definitive, multicenter clinical trial.

Funding support from Canadian Institutes of Health Research (CIHR).

For more information, email sotresearch@bcchr.ca.

Project Status

Status: Pre-enrolment (not yet active)
Study Start Date: November 1, 2024
Study End Date: May 31, 2027

Study Enrolment Status: Active
Start Date: November 1, 2024
End Date: May 31, 2027

Project Team

Principal Investigator

Dr. Tom Blydt-Hansen
 
Co-Investigators

Dr. Li Wang, University of British Columbia (UBC)
Dr. Suzanne Vercauteren, UBC
Dr. Karen Sherwood, UBC
Dr. Paul Keown, UBC
Dr. Aviva Goldberg, University of Manitoba (UM)
Dr. Atul Sharma, UM
Dr. Lusia Sepiashvilli, University of Toronto (U of T)
Dr. Chia Wei Teoh, U of T
Ella Chan, BSc

Research Team Members

Monica Ho, Research Coordinator
Amy Thachil, Research Assistant

Enrolment Eligibility Criteria
  1. Prevalent pediatric kidney transplant recipients (<19 years at transplantation) who are more than 6 months after transplant, with informed consent and assent.
  2. Must be available to follow-up for two years after initiation of urinary CXCL10 monitoring

For more information, email sotresearch@bcchr.ca.