Trifecta-Kidney cfDNA-MMDx Study

January 2, 2024 updated by: Philip Halloran, University of Alberta

Trifecta-Kidney cfDNA-MMDx Study: Comparing the DD-cfDNA Test to MMDx Microarray Test, Central HLA Antibody Test, and Histology.

Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

There is a need for better screening of kidney transplant patients for rejection. Patients with kidney transplants are routinely tested (creatinine, urine protein, histology and donor specific antibody (DSA) as standard of care to detect rejection, but these tests are not adequate. Rejection is often missed by these tests (false negatives) and other processes such as acute kidney injury can produce false-positive results. Moreover, histology has a high interobserver disagreement diagnosing rejection, and cannot accurately assess acute injury. A definitive molecular assessment of rejection and injury in kidney biopsies has emerged - the Molecular Microscope® Diagnostic System (MMDx) - developed by the Alberta Transplant Applied Genomics Centre, University of Alberta. Now a new screening test is being introduced: the monitoring of donor-derived cell-free DNA (DD-cfDNA) released in the blood by the kidney during rejection. The Natera Inc DD-cfDNA Prospera® test is based on the massively multiplex PCR that targets 13,392 single nucleotide polymorphisms and targeted sequences are quantified by Next Generation Sequencing. The Prospera® test done on kidney transplant recipients detected "active rejection" and differentiated it from borderline rejection and no rejection. It is likely, however, that DD-cfDNA test may miss some T cell-mediated rejection (TCMR) cases and the distinction between early and fully developed antibody-mediated rejection (ABMR) was not tested. No study has actually examined the DD-cfDNA results in kidney transplants with acute or chronic kidney disease (AKI and CKD). DD-cfDNA measurements have only been correlated with histology, a flawed standard. DD-cf-DNA test must now be calibrated against MMDx that is based on global gene expression, the new standard for biopsy interpretation. The present study will calibrate centrally measured (Natera Inc) DD-cfDNA levels obtained at the time of an indication biopsy against the MMDx measurements of TCMR, and ABMR (early-stage, fully-developed, and late-stage), AK, and atrophy-fibrosis. We will compare blood DD-cfDNA measurements in 600 samples at the time of 300 indication biopsies to the MMDx results, as well as central assessment of HLA antibody (One Lambda) in 300 blood samples, interpreted centrally as DSA based on the tissue typing results. This study is an extension of the INTERCOMEX ClinicalTrials.gov Identifier: NCT01299168. We have collected 1014 kidney biopsies and corresponding blood samples. Due to considerable interest from participating centers, we extend this study to the total of 1300 biopsies and 3900 blood samples.

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Melbourne, Australia, VIC 3050
        • Recruiting
        • Department of Nephrology, The Royal Melbourne Hospital 1 South East
        • Contact:
        • Principal Investigator:
          • Kevin Chow, MD
        • Sub-Investigator:
          • Peter D Hughes, MD
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2G3
        • Recruiting
        • University of Alberta, Department of Medicine
        • Contact:
        • Principal Investigator:
          • Soroush Shojai, MD
        • Sub-Investigator:
          • Sita Gourishankar, MD
        • Sub-Investigator:
          • Majid Sikosana, MD
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • Recruiting
        • ST. Paul's Hospital, 6A Providence Building, 1081 Burrard Street
        • Contact:
        • Principal Investigator:
          • John S Gill, MD, MS
  • Croatia
      • Zagreb, Croatia, 1910000
        • Recruiting
        • University Hospital Merkur Renal Division
        • Contact:
        • Principal Investigator:
          • Mladen Knotek, MD
        • Sub-Investigator:
          • Zeljka Jurekovic, MD
        • Sub-Investigator:
          • Ksenija Vucur, MD
  • Czechia
      • Prague, Czechia, 140 21 Praha 4
        • Recruiting
        • Institute for Clinical and Experimental Medicine (IKEM)
        • Principal Investigator:
          • Ondrej Viklický, MD
        • Contact:
        • Sub-Investigator:
          • Petra Hruba, MD
        • Sub-Investigator:
          • Silvie Rajnochová Bloudíčkova
  • Germany
  • Lithuania
      • Vilnius, Lithuania, LT-08661
        • Recruiting
        • Centre of Nephrology, Vilnius University Hospital Santaros Klinikos
        • Contact:
        • Principal Investigator:
          • Marius Miglinas, MD
  • Poland
      • Białystok, Poland, 15-540
        • Completed
        • Department of Nephrology and Transplantation Medical University in Bialystok
      • Bydgoszcz, Poland, 85-094
        • Completed
        • University Hospital nr1 Bydgoszcz, Klinika Transplantologii
      • Gdańsk, Poland, 80-259
        • Recruiting
        • Medical University of Gdańsk Klinika Nefrologii Transplantologii i Chorób Wewnętrznych
        • Contact:
        • Principal Investigator:
          • Alicja Dębska-Ślizień, MD
        • Sub-Investigator:
          • Joanna Konopa, MD
        • Sub-Investigator:
          • Andrzej Chamienia, MD
      • Katowice, Poland, 40-027
        • Recruiting
        • Medical University of Silesia
        • Principal Investigator:
          • Grzegorz Piecha, MD
        • Contact:
      • Poznań, Poland, 60-479
        • Recruiting
        • Department of Transplantation and General Surgery, Wojewodzki Hospital
        • Contact:
        • Principal Investigator:
          • Maciej Glyda, MD
        • Sub-Investigator:
          • Katarzyna Smykal-Jankowiak, MD
      • Szczecin, Poland, 70-111
        • Recruiting
        • Department of Nephrology, Transplantation and Internal Medicine, University Hospital n.2
        • Contact:
        • Principal Investigator:
          • Leszek Domański, MD
      • Szczecin, Poland, 71-455
        • Recruiting
        • Pomeranian Medical University, Samodzielny Publiczny Woj. Szpital Zespolony, Oddzial Nefrologii i Transplantacji Nerek
        • Contact:
        • Principal Investigator:
          • Marek Myślak, MD PhD
        • Sub-Investigator:
          • Joanna Mazurkiewicz, MD
        • Sub-Investigator:
          • Marta Gryczman, MD
      • Warsaw, Poland, 02-006
        • Recruiting
        • Medical University of Warsaw, Department of Transplantation Medicine, Nephrology and Internal Diseases
        • Contact:
        • Principal Investigator:
          • Magdalena Durlik, MD
      • Warsaw, Poland, 02-006
        • Recruiting
        • Transplant Medicine & Nephrology Clinic, Medical University of Warsaw
        • Contact:
        • Principal Investigator:
          • Agnieszka Perkowska-Ptasińska, MD PhD
        • Sub-Investigator:
          • Dominika Dęborska-Materkowska, MD
        • Sub-Investigator:
          • Michał Ciszek, MD
      • Warsaw, Poland, 04-730
        • Completed
        • The Children's Memorial Health Institute, Department of Nephrology, Kidney Transplantation and Hypertension
      • Wrocław, Poland, 50-556
        • Recruiting
        • Wroclaw Medical University, Department of Nephrology and Transplantation Medicine
        • Contact:
        • Principal Investigator:
          • Mirosław Banasik, MD
  • Slovenia
      • Ljubljana, Slovenia, 21000
        • Recruiting
        • Department of Nephrology, University Medical Centre
        • Contact:
        • Principal Investigator:
          • Miha Arnol, MD
        • Sub-Investigator:
          • Nika Kojc, MD
  • Switzerland
      • Zürich, Switzerland, 8091
        • Recruiting
        • University Hospital Zurich
        • Contact:
        • Principal Investigator:
          • Thomas Muller, MD PhD
        • Sub-Investigator:
          • Thomas Schachtner, MD
  • United States
    • Florida
      • Tampa, Florida, United States, 33606
        • Recruiting
        • Tampa General Hospital
        • Contact:
        • Principal Investigator:
          • Rajendra Baliga, MD
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland School of Medicine
        • Contact:
        • Principal Investigator:
          • Jonathan Bromberg, MD PhD
        • Principal Investigator:
          • Matt Weir, MD
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • The Johns Hopkins University, School of Medicine
        • Contact:
        • Principal Investigator:
          • Daniel C Brennan, MD
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Principal Investigator:
          • Milagros Samaniego-Picota, MD
        • Contact:
        • Sub-Investigator:
          • Iman Francis, MD
        • Sub-Investigator:
          • Anita Patel, MD
      • Detroit, Michigan, United States, 48201
        • Not yet recruiting
        • Detroit Medical Center, Harper University Hospital of Wayne State University
        • Contact:
        • Principal Investigator:
          • Rajeev Sharma, MD
        • Sub-Investigator:
          • Mareena Zachariah, MD
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Barnes-Jewish Hospital, Washington University at St. Louis
        • Contact:
        • Principal Investigator:
          • Andrew Malone, MD PhD
        • Sub-Investigator:
          • Tarek Ahamad, MD
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Principal Investigator:
          • Richard Fatica, MD
        • Principal Investigator:
          • Ziad Zaky, MD
        • Contact:
        • Principal Investigator:
          • Emillio Poggio, MD
      • Cleveland, Ohio, United States, 44106-5048
        • Recruiting
        • University Hospitals Cleveland Medical Ctr.
        • Contact:
        • Principal Investigator:
          • Jittirat Arksarapuk, MD
    • Utah
      • Murray, Utah, United States, 84107
        • Recruiting
        • Intermountain Transplant Services
        • Contact:
        • Principal Investigator:
          • Sanjiv Anand, MD
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University Medical Center
        • Contact:
        • Principal Investigator:
          • Layla Camal, MD
        • Principal Investigator:
          • Gaurav Gupta, MD
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • Division of Nephrology & UW Organ Transplant Center University of Washington
        • Contact:
        • Principal Investigator:
          • Chris Bosser, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care to determine the cause of their graft dysfunction (deterioration in graft function, delayed graft function, proteinuria).

Description

Inclusion Criteria:

  • All kidney transplant recipients undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enroll in the study.

Exclusion Criteria:

  • Patients will be excluded from the study if they decline participation or are unable to give informed consent or multiple organ recipients.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Kidney transplant biopsies for cause
The study population includes patients with a functioning kidney transplant undergoing a biopsy for clinical indications as standard of care.
Diagnostic test: MMDx
Portion of kidney transplant indication biopsy
Diagnostic test: Prospera
Transplant patient blood sample
Other Names:
  • transplant patient blood sample
Diagnostic test: HLA antibody
Transplant patient blood sample
Other Names:
  • transplant patient blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Calibration of Prospera test for T cell-mediated rejection
Time Frame: 18 months
Calibration of DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx.
18 months
Calibration of Prospera test for antibody-mediated rejection
Time Frame: 18 months
Calibration of DD-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy as reported by MMDx.
18 months
Calibration of Prospera test for kidney injury
Time Frame: 18 months
Calibration of DD-cfDNA test cut-off values against the probability of acute and chronic kidney injury in the biopsy as reported by MMDx.
18 months
Report calibrated Prospera test results for rejection
Time Frame: 6 months
Report new DD-cfDNA test cut-off values for rejection
6 months
Report calibrated Prospera test results for kidney injury
Time Frame: 6 month
Report new DD-cfDNA test cut-off values for acute and chronic kidney injury
6 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine if Prospera blood test can replace kidney biopsy test
Time Frame: 6 months
Determine if Prospera test, as calibrated by this DD-cfDNA-HLA-MMDx study, will avoid need for indication biopsy when kidney transplant function deteriorates. This will be based on the consensus between participating clinicians.
6 months
Assessment of donor-specific antibody status
Time Frame: 6 months
Report and compare the DSA status based on centralized and local HLA antibody measurement.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alberta

Collaborators

Natera, Inc.
One Lambda

Investigators

  • Principal Investigator: Philip F Halloran, MD, PhD, University of Alberta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2019

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

January 14, 2020

First Submitted That Met QC Criteria

January 23, 2020

First Posted (Actual)

January 27, 2020

Study Record Updates

Last Update Posted (Actual)

January 5, 2024

Last Update Submitted That Met QC Criteria

January 2, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATAGC05

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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