Urine CXCL10 Monitoring for Kidney Transplant Rejection

Not currently recruiting at 10 trial locations

Overseen By Michelle Lesyk, RN, BN

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Manitoba

Must be taking: Calcineurin inhibitors

Disqualifiers: Blood group incompatible, DSA positive, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to detect kidney transplant rejection early by identifying a marker in urine called CXCL10. The goal is to determine if treating this early sign of rejection can improve the long-term health of the transplanted kidney. Participants with a kidney transplant and high CXCL10 levels might undergo a biopsy (a small tissue test) to check for rejection. Those with high urine CXCL10 levels and no urinary tract infection are suitable candidates for this trial. As a Phase 2, Phase 3 trial, the research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval. Participants have the opportunity to contribute to potentially groundbreaking advancements in kidney transplant care.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should intend to use a maintenance immunosuppression regimen with specific drugs, so you may need to adjust your medications accordingly.

What prior data suggests that this protocol is safe for kidney transplant patients?

Research has shown that kidney transplant biopsies, like those used in this trial to check for rejection, are generally safe. A biopsy involves taking a small piece of kidney tissue to look for signs of rejection.

Studies have found that most patients handle these biopsies well. While some risks exist, such as bleeding or infection, serious problems are rare. Doctors use imaging tools, like ultrasound, to guide the needle and reduce risks.

For those considering joining a trial that includes a kidney biopsy, it's important to know that these procedures have been safely used in many other studies and medical settings. Discuss any concerns with a healthcare provider to ensure all necessary information is available. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores using urine CXCL10 levels to potentially identify kidney transplant rejection earlier and more accurately than current methods, like regular blood tests and biopsies. Current options often involve detecting rejection after damage has occurred, but this approach aims to catch signs of trouble earlier, potentially before symptoms appear. By identifying rejection sooner, doctors might be able to intervene more effectively, improving outcomes for transplant patients.

What evidence suggests that this trial's treatments could be effective for kidney transplant rejection?

Research has shown that urinary CXCL10 could be useful for monitoring kidney transplant health. This marker might help detect early problems, such as rejection, when the body attacks the new kidney. In this trial, participants with high urine CXCL10 levels will be randomized into different arms. Those in the Intervention Arm will undergo a kidney transplant biopsy to check for rejection, with biopsy-proven subclinical rejection treated per study protocol. Meanwhile, participants in the Control Arm will continue routine post-transplant surveillance without biopsy intervention. Previous studies have not demonstrated that monitoring CXCL10 alone improves one-year outcomes. However, early detection using this method might still help maintain kidney health over time. The current focus is on whether early detection can lead to better results for kidney transplant patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Julie Ho, MD

Principal Investigator

University of Manitoba

Are You a Good Fit for This Trial?

Adults over 18 who've recently had a kidney transplant can join this trial. They must understand the study, agree to follow its rules, and be available for its duration. Participants need an elevated urine CXCL10 level without infection or significant bleeding in their urine. Those with certain immune mismatches, other organ transplants, conditions affecting safe participation or data quality, incompatible blood types, high antibody levels against the donor kidney, or not following standard anti-rejection drugs cannot join.

Inclusion Criteria

Participants must be able to understand and provide written informed consent

Confirmed elevated urine CXCL10:Cr without a urinary tract infection or gross hematuria.

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

I have antibodies against the transplant donor.

I have had an organ transplant.

My organ transplant has failed to work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Post-transplant Surveillance

Routine urine CXCL10 screening from 2 weeks to 9 months post-transplant to monitor for elevated levels indicating risk of rejection

9 months

Intervention

Participants with high urine CXCL10 undergo randomization; intervention arm receives kidney biopsy and treatment for subclinical rejection, control arm continues routine surveillance

12 months

12-month study exit visit with protocol biopsy

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of long-term outcomes

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Kidney transplant biopsy

Trial Overview The trial is testing if treating kidney transplant rejection early based on urinary CXCL10 levels improves long-term outcomes of the new kidney. It's a controlled study where some patients will receive treatment based on these biomarker levels while others may follow standard care protocols.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Participants with high urine CXCL10 randomized to the Intervention Arm will undergo a kidney transplant biopsy to check for rejection. Biopsy-proven subclinical rejection will be treated per study protocol.

Group II: Control Active Control 1 Intervention

Participants with high urine CXCL10 randomized to the Control Arm will continue routine post-transplant surveillance with serum creatinine and proteinuria; serial urine samples will continue to be collected and analyzed (blinded), but not used to direct care.

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Canadian National Transplant Research Program

Collaborator

Trials

9

Recruited

1,600+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10919271/

Urine CXCL10 as a biomarker in kidney transplantation Urine CXCL10 is a promising biomarker for posttransplant renal allograft monitoring but is currently not widely used for clinical management.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03206801

Urine CXCL10 Monitoring Trial in Kidney Transplant The primary objective of this study is to determine if the early treatment of rejection, as detected by urinary CXCL10, will improve renal allograft outcomes.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11375915/

Urinary CXCL-10, a prognostic biomarker for kidney graft ... The aim of this review is to analyze the literature on the potential role of urinary CXCL10 protein in predicting kidney graft injuries.

4. nature.com nature.com/articles/s41598-024-70390-x

Transforming kidney transplant monitoring with urine ... Overall, our linearity and recovery data support the following LLOQ and ULOQ on urine sample: 39.8–2000 pg/mL (CXCL9) and 0.6–920 pg/mL (CXCL10) ...

5. journals.lww.com journals.lww.com/jasn/fulltext/2023/08000/randomized_trial_to_assess_the_clinical_utility_of.16.aspx

Randomized Trial to Assess the Clinical Utility of Renal... Although urine CXCL10 monitoring could not demonstrate a beneficial effect on 1-year outcomes, the study is a rich source for future design of trials aiming to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03206801

Urine CXCL10 Monitoring Trial in Kidney Transplant The primary objective of this study is to determine if the early treatment of rejection, as detected by urinary CXCL10, will improve renal allograft outcomes.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6500325/

Multicentre randomised controlled trial protocol of urine ... Urine CXCL10 outperforms standard post-transplant surveillance in observational studies, by detecting subclinical rejection and early clinical rejection.

8. journals.lww.com journals.lww.com/jasn/fulltext/9900/detection_of_kidney_allograft_rejection_using.673.aspx

Detection of Kidney Allograft Rejection Using Urinary... Urinary CXCL9 demonstrated limited clinical utility, while urinary CXCL10 provided no additional value beyond standard-of-care monitoring for ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522085021

Validity and utility of urinary CXCL10/Cr immune ... Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function.

10. clinicaltrial.be clinicaltrial.be/en/details/71126?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Urine CXCL10 Monitoring Trial in Kidney Transplant - Clin... Two hundred and fifty patients deemed at high risk for rejection based on a confirmed elevated urine CXCL10 will undergo 1:1 randomization to ...