NCT06288425

Brief Summary

The study is an investigator-led, prospective, longitudinal, observational cohort study. The central hypothesis for this study is that spatial data will reveal new insights to immune cell function and local interactions within the kidney tissue to better predict important clinical outcomes. Investigators aspire to establish a prospective, longitudinal cohort to improve the diagnosis and management of kidney transplant rejection using precision pathology. By utilising new spatial technologies, the investigators aim to:

  • Derive a spatially resolved transcriptomic signature of kidney transplant rejection subtypes
  • Derive accurate transcriptomic signatures aligned with key cell types within the transplant kidney
  • Develop refinements to histological kidney rejection diagnostic and scoring classification
  • Correlate of spatial and refined biopsy scoring features to clinically important outcomes

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
500

participants targeted

Target at P75+ for all trials

Timeline
105mo left

Started Apr 2024

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
enrolling by invitation

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress19%
Apr 2024Jan 2035

First Submitted

Initial submission to the registry

February 3, 2024

Completed
27 days until next milestone

First Posted

Study publicly available on registry

March 1, 2024

Completed
1 month until next milestone

Study Start

First participant enrolled

April 3, 2024

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2030

Expected
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2035

Last Updated

April 24, 2024

Status Verified

April 1, 2024

Enrollment Period

5.8 years

First QC Date

February 3, 2024

Last Update Submit

April 22, 2024

Conditions

Transplant ComplicationKidney Injury

Outcome Measures

Primary Outcomes (3)

  • Kidney biopsy features

    Based on the pathology subtype at original diagnosis

    At biopsy or during study follow up following biopsy during study (expected 12-months)

  • Kidney biopsy transcriptomic signature

    Based on bulk and/or spatial transcriptomic experiments

    At biopsy - based on collected tissue sample

  • Kidney cell type composition

    Cell type phenotyping of immune and kidney cell types

    At biopsy - based on collected tissue sample

Secondary Outcomes (14)

  • All cause graft loss

    At biopsy or during study follow up after biopsy (expected average over 60-months)

  • Death censored graft loss (DCGL)

    At biopsy or during study follow up after biopsy (expected average over 60-months)

  • Treatment resistant rejection

    At biopsy or during study follow up after biopsy (expected average 12-months)

  • Delayed graft function (DGF)

    At biopsy or during study follow up after biopsy (within 7 days of transplantation)

  • Biopsy evidence of borderline rejection

    At biopsy or during study follow up after biopsy (expected average 12-months)

  • +9 more secondary outcomes

Study Arms (8)

No rejection, normal biopsy (controls)

Normal biopsy - no acute tubular injury (ATI), rejection or any other pathology

Other: Non interventional

Acute kidney injury without evidence of rejection

Biopsy features of acute tubular injury but no evidence of rejection

Other: Non interventional

Subclinical Rejection

Biopsy features of injury and inflammation but not meeting current diagnostic criteria for acute or chronic rejection

Other: Non interventional

Acute rejection

Biopsy features of T-cell mediated, antibody-mediated, or mixed rejection

Other: Non interventional

Isolated vascular rejection

Biopsy features of inflammation in the blood vessels only

Other: Non interventional

Isolated glomerulitis

Biopsy features of inflammation in the glomeruli only

Other: Non interventional

Chronic (active) rejection

Biopsy features of chronic rejection - T-cell, antibody or mixed types

Other: Non interventional

BK virus associated nephropathy (BKVAN)

Biopsy features of SV40 positive staining in tubules to diagnose BKVAN

Other: Non interventional

Interventions

Non interventionalOTHER

Non interventional. Review of clinical, biopsy (histopathological and molecular) features associated with rejection and non-rejection pathology diagnosis

Acute kidney injury without evidence of rejectionAcute rejectionBK virus associated nephropathy (BKVAN)Chronic (active) rejectionIsolated glomerulitisIsolated vascular rejectionNo rejection, normal biopsy (controls)Subclinical Rejection

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Kidney transplant (or kidney-pancreas transplant) recipients consenting to this study.

You may qualify if:

  • All participants included in the study must be age ≥ 18 years old at time of enrolment and
  • able to provide informed consent (interpreter permitted) for enrolment
  • consenting to longitudinal follow up (can withdraw post enrolment)
  • consenting to provide samples for biobanking, including blood, urine, faecal and/or kidney biopsy tissue (collected prospectively, separate to routine care)

You may not qualify if:

  • Patients will be excluded from the study if they are
  • unable (or unwilling) to provide consent, or
  • have life-expectancy less than 6-months, or
  • have received a haematopoietic stem cell transplant in the past 5 years.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Biospecimen

Retention: SAMPLES WITH DNA

Dedicated study samples will be collected at baseline and additional time-points based on the study group. Samples will be sent for processing and biobanking at the Westmead Institute for Medical Research Blood sampling: all patients will submit blood samples for extraction of genomic material (eg DNA, RNA), peripheral blood mononuclear cells (PBMC) and plasma/serum. Kidney biopsy sample: a dedicated sample of kidney biopsy may be collected for the study with the patient's permission. The core will be split so that half the sample is collected in specialised media for spatial transcriptomics and other molecular/proteinomic studies. Additional sampling: Mid-stream urine sample for pellet and supernatant and then stored at -80'c, Faecal sample in dedicated gut microbiome kits and then stored at -80'c. These samples will be biobanked and may be used later for proteinomic or microbiome studies.

Study Officials

  • Jen Li, FRACP

    Westmead Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
CPI, Nephrologist and Transplant Physician

Study Record Dates

First Submitted

February 3, 2024

First Posted

March 1, 2024

Study Start

April 3, 2024

Primary Completion (Estimated)

January 1, 2030

Study Completion (Estimated)

January 1, 2035

Last Updated

April 24, 2024

Record last verified: 2024-04

Data Sharing

IPD Sharing
Will not share

Locations

AU(1)