Trifecta-Lung cfDNA-MMDx Study

June 1, 2026 updated by: University of Alberta

Trifecta-Lung cfDNA-MMDx Study: Comparing the Dd-cfDNA Test to MMDx Microarray Test and Central HLA Antibody Test

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

Study Overview

Status

Recruiting

Conditions

Detailed Description

The current standard for assessment of rejection in lung transplants is a transbronchial biopsy (TBB) interpreted by histology according to International Society of Heart and Lung Transplantation (ISHLT) guidelines. This has considerable error rates, many due to the high disagreement among pathologists. There is a need for new methods of assessing TBBs. Furthermore, by analyzing different types of biopsies (TBBs and endobronchial - 3BMBs), we hope to improve the safety of the biopsy procedure, while maintaining its accuracy. The emergence of blood donor-derived cell-free DNA (dd-cfDNA) measurement offers a new opportunity for screening for rejection. 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 genome-wide gene expression and interpret lung transplant rejection and injury ((chronic lung allograft dysfunction (CLAD) related changes)). Now a new screening test is being introduced: the monitoring of 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 lung transplant recipients. dd-cf-DNA test for lung 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-like) and tissue injury. The present study will compare dd-cfDNA and MMDx in 600 prospectively collected TBBs and 3BMBs for clinical indications and protocol, and accompanying 1800 blood samples, to calibrate the dd-cfDNA (Natera Inc.) levels against the MMDx biopsy diagnoses of TCMR, ABMR-like (and its stages), and injury, as well as central assessment of Human Leukocyte Antibody (HLA) antibody (One Lambda), interpreted centrally as donor specific antibody (DSA) based on the tissue typing results. This study is an extension of the INTERLUNG ClinicalTrials.gov identifier: NCT02812290.

Currently the study accrued 141 paired TBBs and 3BMBs, 182 TBBs, 267 corresponding blood samples for dd-cfDNA test and 159 for DSA test.

Study Type

Observational

Enrollment (Estimated)

600

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
        • Recruiting
        • The Alfred Hospital, Monash University
        • Principal Investigator:
          • Greg Snell, Professor
        • Contact:
        • Principal Investigator:
          • Glen Westall, MD PhD
  • Austria
      • Vienna, Austria
        • Not yet recruiting
        • Department of Thoracic Surgery, Medical University of Vienna
        • Contact:
        • Principal Investigator:
          • Konrad Hoetzenecker, Professor
        • Sub-Investigator:
          • Peter Jaksch, MD
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2G3
        • Recruiting
        • Department of Medicine, University of Alberta
        • Sub-Investigator:
          • Justin Weinkauf, MD
        • Sub-Investigator:
          • Alim Hirji, MD
        • Contact:
        • Principal Investigator:
          • Kieran Halloran, MD MSc
      • Edmonton, Alberta, Canada, T^g 2E1
        • Recruiting
        • Alberta Transplant Applied Genomics Centre, University of Alberta
        • Principal Investigator:
          • Philip F Halloran, MD PhD
        • Contact:
        • Contact:
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • University Health Network, Toronto General Hospital
        • Principal Investigator:
          • Shaf Keshavjee, MD MSc
        • Contact:
        • Principal Investigator:
          • Stephen Juvet, MD PhD
  • Czechia
      • Prague, Czechia
        • Recruiting
        • Charles University/Hospital Motol
        • Contact:
        • Principal Investigator:
          • Jan Havlin, MD
      • Prague, Czechia, 15006
        • Recruiting
        • Motol University Hospital, V Uvalu 84
        • Principal Investigator:
          • Jan Havlin, MD
        • Contact:
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Recruiting
        • St. Joseph's Hospital and Medical Center 350 West Thomas Road, Floor 8HLT
        • Principal Investigator:
          • Rajat Walia, MD
        • Contact:
    • Florida
      • Gainesville, Florida, United States, 32610
        • Recruiting
        • Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, College of Medicine
        • Contact:
        • Principal Investigator:
          • Amir Emtiazjoo, MD, MSc
        • Sub-Investigator:
          • Christina Eagan, MD
        • Sub-Investigator:
          • Hiren Mehta, MD
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Mayo Clinic Florida, 4500 San Pablo Rd
        • Principal Investigator:
          • Remzi Bag, MD
        • Contact:
      • Tampa, Florida, United States, 33612
        • Recruiting
        • USF Health, Morsani College of Medicine, 12901 Bruce B. Downs Blvd. MDC40
        • Contact:
        • Principal Investigator:
          • Ishna Poojary-Hohman, MD
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University Methodist Hospital 1812 N. Capitol Ave Suite W131L
        • Contact:
        • Principal Investigator:
          • Nikki Smith, MD
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins Interventional Pulmonology, Sheikh Zayed Tower, Room 7125L, 1800 Orleans Street
        • Contact:
        • Principal Investigator:
          • Jeffrey Thiboutot, MD MHS
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Division of Pulmonary, Allergy & Critical Care Medicine Columbia University Irving Medical Center
        • Contact:
        • Principal Investigator:
          • Kemarut Laothmatas, MD
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • The Ohio State University Wexner Medical Center, 410 W 10th Ave
        • Principal Investigator:
          • Justin Rosenheck, DO
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75246
        • Recruiting
        • BAYLOR SCOTT & WHITE RESEARCH INSTITUTE , 3409 Worth Street
        • Contact:
        • Sub-Investigator:
          • Todd Grazia, MD
        • Principal Investigator:
          • Samir Kumar, MD MBA
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern Medical Center, 5939 Harry Hines Blvd.
        • Contact:
        • Principal Investigator:
          • Irina L Timofte, MD
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist Lung Transplant Center, 6550 Fannin St., SM1001
        • Principal Investigator:
          • Howard J Huang, MD
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • UT Health San Antonio 7703 Floyd Curl Drive, MSC: 7858
        • Contact:
        • Principal Investigator:
          • Lara Jones, DO

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

All adult lung transplant recipients undergoing indication biopsy for suspected graft dysfunction will be eligible.

Description

Inclusion Criteria:

Adult, Older adult

Exclusion Criteria:

Patients will be excluded from the study if they decline participation Are unable to give informed consent. Recipients of multiple organs, cancer patients and pregnant women

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 lung injury
Time Frame: 6 months
Report new DD-cfDNA test cut-off values for lung injury
6 months
Calibration of Prospera® test for T cell mediated rejection
Time Frame: 18 months
Set dd-cfDNA test cut-off values against the probability of T cell-mediated rejection in the biopsy (TBB and 3BMB) 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.
18 months
Calibration of Prospera® test for antibody-mediated rejection
Time Frame: 18 months
Set dd-cfDNA test cut-off values against the probability of antibody-mediated rejection in the biopsy (TBB and 3BMB) as reported by MMDx.
18 months
Calibration of Prospera® test for lung injury
Time Frame: 18 months
Set dd-cfDNA test cut-off values against the probability of acute and chronic lung injury in the biopsy (TBB and 3BMB)as reported by MMDx.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of donor-specific antibody status
Time Frame: 6 months
Record and compare the DSA status (positive or negative) based on centralized and local HLA antibody to histology diagnoses..
6 months
.Estimate the false positive rate of dd-cfDNA for MMDx and histology in indication and protocol biopsies
Time Frame: 6 months
Calculate the sensitivity and specificity of dd-cfDNA for MMDx and histology diagnoses.
6 months
Determine whether calibrated dd-cfDNA blood test will replace biopsies
Time Frame: 6 months
Determine if dd-cfDNA test will avoid need for indication biopsy when transplant function deteriorates - yes or no. This will be based on the consensus between participating clinicians.
6 months
Determine whether calibrated dd-cfDNA blood test predicts the effect of treatment
Time Frame: 6 months
Determine the values for dd-cfDNA for grades of response to treatment: no change, partial response, complete resolution.
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, Alberta Transplant Applied Genomics Centre, University of Alberta

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)

November 1, 2023

Primary Completion (Estimated)

November 1, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

April 3, 2023

First Submitted That Met QC Criteria

April 18, 2023

First Posted (Actual)

May 1, 2023

Study Record Updates

Last Update Posted (Actual)

June 2, 2026

Last Update Submitted That Met QC Criteria

June 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • Pro00048176

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Only IPD data will be shared within a participating center

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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