Summary

Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Martin Cadeiras (ucla)

Description

Summary

Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood transplant recipient and the Molecular Microscope® (MMDx) Diagnostic System results in indication and protocol biopsies from heart transplants.

Official Title

Trifecta-Heart cfDNA-MMDX Study: Comparing the DD-cfDNA Test to MMDx Microarray Test and Central HLA Antibody Test

Details

The current standard for assessment of rejection in heart transplants is an endomyocardial biopsy (EMB) interpreted by histology according to ISHLT guidelines. This has considerable error rates, many due to the high disagreement among pathologists in assessing lesions and diagnoses. To address the unmet need for precision and accuracy, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx), which uses microarrays to define the global gene expression features of rejection and injury. Now a new screening test is being introduced: the monitoring of donor-derived cell-free DNA (DD-cfDNA) released in the blood by the heart during rejection. The Natera Inc DD-cfDNA Prospera® test is based on the massively multiplex polymerase chain reaction that targets 13,392 single nucleotide polymorphisms and targeted sequences are quantified by Next Generation Sequencing. The Prospera® test has been done on kidney transplant recipients and detected "active rejection" and differentiated it from borderline rejection and no rejection. However, Prospera® test was not examined (the DD-cfDNA results) in heart transplant recipients. DD-cf-DNA test for heart transplants 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 or protocol biopsy against the MMDx measurements of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR) and early and late tissue injury. The present study will compare DD-cfDNA and MMDx in 300 prospectively collected biopsies for clinical indications and protocol, and accompanying 600 blood samples, to calibrate the DD-cfDNA (Natera Inc.) levels against the MMDx biopsy diagnoses of TCMR, ABMR (and its stages), and acute (early) and chronic (late) injury, , as well as central assessment of HLA antibody (One Lambda) in 300 blood samples, interpreted centrally as donor specific antibody (DSA) based on the tissue typing results. Due to a considerable interest from participation centers, we extend this study to 700 biopsies and corresponding blood samples. This study is an extension of the INTERHEART ClinicalTrials.gov Identifier: NCT02670408

Keywords

Heart Transplant Rejection Donor derived cfDNA gene expression heart transplant biopsy Antibodies MMDx diagnostic test Prospera HLA antibody Heart transplant protocol and for cause biopsies

Eligibility

You can join if…

  • All heart transplant recipients undergoing a biopsy for clinical indications and protocol biopsies, as determined by their physician or surgeon, will be eligible to enroll in the study.
  • Patients are enrolled based on standard of care biopsies, including surveillance biopsies in high-risk patients, with informed consent.

You CAN'T join if...

  • Patients will be excluded from the study if they decline participation
  • Are unable to give informed consent.
  • Recipients of multiple organs.

Locations

  • UCLA Medical Centre not yet accepting patients
    Los Angeles California 90024 United States
  • Cedars-Sinai Heart Institute not yet accepting patients
    Los Angeles California 90048 United States

Lead Scientist at University of California Health

Details

Status
accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
(estimated)
Sponsor
University of Alberta
ID
NCT04707872
Study Type
Observational
Participants
Expecting 300 study participants
Last Updated