Brief 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.
Brief Title
Trifecta-Heart cfDNA-MMDx Study
Detailed 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 575 biopsies and 573 cfDNA samples, and 573 One Lambda samples so far. Due to a considerable interest from participation centers, this study aims to collect 300 more biopsies and corresponding blood samples. This study is an extension of the INTERHEART ClinicalTrials.gov Identifier: NCT02670408
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1 780 782 9463
Central Contact Email
konrad@ualberta.ca
Central Contact Role
Contact
Central Contact Phone
1 780 492 5091
Central Contact Email
polakows@ualberta.ca
Completion Date
Completion Date Type
Estimated
Conditions
Heart Transplant Rejection
Eligibility Criteria
Inclusion Criteria:
* 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.
Exclusion Criteria:
* Patients will be excluded from the study if they decline participation
* Are unable to give informed consent.
* Recipients of multiple organs.
* 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.
Exclusion Criteria:
* Patients will be excluded from the study if they decline participation
* Are unable to give informed consent.
* Recipients of multiple organs.
Inclusion Criteria
Inclusion Criteria:
* 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.
* 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.
Gender
All
Gender Based
false
Keywords
Donor derived cfDNA
gene expression
heart transplant biopsy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
NCT Id
NCT04707872
Org Class
Other
Org Full Name
University of Alberta
Org Study Id
ATAGC06
Overall Status
Recruiting
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
Trifecta-Heart cfDNA-MMDX Study: Comparing the DD-cfDNA Test to MMDx Microarray Test and Central HLA Antibody Test
Primary Outcomes
Outcome Description
Set DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx. Calibration of DD-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy as reported by MMDx.
Outcome Measure
Calibration of Prospera test for T cell-mediated rejection
Outcome Time Frame
18 months
Outcome Description
Set DD-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy as reported by MMDx.
Outcome Measure
Calibration of Prospera test for antibody-mediated rejection
Outcome Time Frame
18 months
Outcome Description
Set DD-cfDNA test cut-off values against the probability of acute and chronic heart injury in the biopsy as reported by MMDx.
Outcome Measure
Calibration of Prospera test for heart injury
Outcome Time Frame
18 month
Outcome Description
Obtain clinicians feedback
Outcome Measure
Report calibrated Prospera test results for rejection
Outcome Time Frame
6 months
Outcome Description
Obtain clinicians feedback
Outcome Measure
Report calibrated Prospera test results for heart injury
Outcome Time Frame
6 month
Secondary Outcomes
Outcome Description
Obtain clinicians feedback
Outcome Time Frame
6 month
Outcome Measure
Determine if Prospera blood test can replace heart biopsy test
Outcome Description
Determine whether resolution of DD-cfDNA after treatment can monitor response to therapy and avoid follow-up biopsies
Outcome Time Frame
6 month
Outcome Measure
Determine if Prospera blood test can replace follow up heart biopsy
Outcome Description
Report and compare the DSA status based on centralized and local HLA antibody measurement.
Outcome Time Frame
6 months
Outcome Measure
Assessment of donor-specific antibody status
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Study Population
The study population includes patients with a functioning heart transplant undergoing a biopsy for clinical indications or surveillance (protocol) biopsy.
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Omar Saeed
Investigator Email
osaeed@montefiore.org