We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trifecta-Kidney cfDNA-MMDx Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04239703
Recruitment Status : Recruiting
First Posted : January 27, 2020
Last Update Posted : March 31, 2023
Sponsor:
Collaborators:
Natera, Inc.
One Lambda
Information provided by (Responsible Party):
Philip Halloran, University of Alberta

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.

Condition or disease Intervention/treatment
Kidney Transplant Rejection Diagnostic Test: MMDx Diagnostic Test: Prospera Diagnostic Test: HLA antibody

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 Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Estimated Enrollment : 300 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Trifecta-Kidney cfDNA-MMDx Study: Comparing the DD-cfDNA Test to MMDx Microarray Test, Central HLA Antibody Test, and Histology.
Actual Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: transplant patient blood sample

Diagnostic Test: HLA antibody
Transplant patient blood sample
Other Name: transplant patient blood sample


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Report calibrated Prospera test results for rejection [ Time Frame: 6 months ]
    Report new DD-cfDNA test cut-off values for rejection

  5. 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


Secondary Outcome Measures :
  1. 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.

  2. Assessment of donor-specific antibody status [ Time Frame: 6 months ]
    Report and compare the DSA status based on centralized and local HLA antibody measurement.


Biospecimen Retention:   Samples Without DNA
RNA isolated from kidney biopsies

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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).
Criteria

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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04239703


Contacts
Layout table for location contacts
Contact: Konrad S Famulski, PhD 1 780 492 1725 konrad@ualberta.ca
Contact: Robert Polakowski, PhD 1 780 492 5091 polakows@ualberta.ca

Locations
Show Show 31 study locations
Sponsors and Collaborators
University of Alberta
Natera, Inc.
One Lambda
Investigators
Layout table for investigator information
Principal Investigator: Philip F Halloran, MD, PhD University of Alberta
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Philip Halloran, Distinguished Professor, University of Alberta
ClinicalTrials.gov Identifier: NCT04239703    
Other Study ID Numbers: ATAGC05
First Posted: January 27, 2020    Key Record Dates
Last Update Posted: March 31, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Philip Halloran, University of Alberta:
donor derived cell-free DNA
blood
kidney biopsy
Additional relevant MeSH terms:
Layout table for MeSH terms
Antibodies
Immunologic Factors
Physiological Effects of Drugs