Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

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. Trifecta-Heart collected 258 biopsies and 216 corresponding cfDNA samples. Due to a considerable interest from participation centers, this study aims to collect 400 biopsies and corresponding blood samples. This study is an extension of the INTERHEART ClinicalTrials.gov Identifier: NCT02670408 ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04707872
Study type Observational
Source University of Alberta
Contact Konrad Famulski, PhD
Phone 1 780 782 9463
Email konrad@ualberta.ca
Status Recruiting
Phase
Start date June 1, 2021
Completion date July 2025

See also
  Status Clinical Trial Phase
Active, not recruiting NCT05205551 - Prospera Test Evaluation in Cardiac Transplant (ProTECT)
Not yet recruiting NCT05732779 - Mobile Video Directly Observed Therapy (DOT) for Immunosuppression Medication Adherence in Adolescent Heart Transplant Recipients N/A
Active, not recruiting NCT05064462 - TTV Viral Load in Heart Transplant Recipients
Recruiting NCT04973943 - Donor-derived Cell Free DNA as a New Biomarker in Cardiac Acute Rejection
Completed NCT03477383 - A New Biomarker for the Non-invasive Diagnosis of Rejection After Heart Transplantation
Not yet recruiting NCT05772442 - Cardiac Transplant Metabolomics With and Without Rejection
Recruiting NCT06064123 - Biomarkers for Diagnosis, Prognosis, and Targeted Therapy After Heart Transplantation
Active, not recruiting NCT04921774 - Research on Patients With Heart Transplantation
Recruiting NCT04226521 - Extracorporeal Photopheresis and Early Cardiac Graft Vasculopathy N/A
Completed NCT03393793 - HEart trAnsplantation Registry of piTie-Salpetriere University Hospital
Completed NCT01136135 - Cardiac Magnetic Resonance Imaging (CMRI) for Detection of Cardiac Transplant Rejection N/A
Completed NCT03833050 - The TOGETHER Project - Heart
Active, not recruiting NCT03373227 - Phase II Study Evaluating the Efficacy of Tacrolimus Extended Release Tablets to Twice Daily Tacrolimus Dosing Regimen Phase 2
Active, not recruiting NCT03695601 - Surveillance HeartCare® Outcomes Registry
Active, not recruiting NCT01397812 - Heartsbreath Test for Heart Transplant Rejection N/A
Active, not recruiting NCT05184426 - MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)