Trifecta-Lung cfDNA-MMDx Study

NCT ID: NCT05837663

Last Updated: 2026-01-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

600 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-11-01

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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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 108 paired TBBs and 3BMBs, 9 TBBs, and 64 corresponding blood samples for dd-cfDNA test.

Conditions

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Lung Transplantation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Natera, Inc.

INDUSTRY

Sponsor Role collaborator

One Lambda

UNKNOWN

Sponsor Role collaborator

University of Alberta

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Philip F Halloran, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Alberta Transplant Applied Genomics Centre, University of Alberta

Locations

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St. Joseph's Hospital and Medical Center 350 West Thomas Road, Floor 8HLT

Phoenix, Arizona, United States

Site Status RECRUITING

Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, College of Medicine

Gainesville, Florida, United States

Site Status RECRUITING

USF Health, Morsani College of Medicine, 12901 Bruce B. Downs Blvd. MDC40

Tampa, Florida, United States

Site Status RECRUITING

Indiana University Methodist Hospital 1812 N. Capitol Ave Suite W131L

Indianapolis, Indiana, United States

Site Status RECRUITING

Johns Hopkins Interventional Pulmonology, Sheikh Zayed Tower, Room 7125L, 1800 Orleans Street

Baltimore, Maryland, United States

Site Status RECRUITING

Division of Pulmonary, Allergy & Critical Care Medicine Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

The Ohio State University Wexner Medical Center, 410 W 10th Ave

Columbus, Ohio, United States

Site Status RECRUITING

BAYLOR SCOTT & WHITE RESEARCH INSTITUTE , 3409 Worth Street

Dallas, Texas, United States

Site Status RECRUITING

UT Southwestern Medical Center, 5939 Harry Hines Blvd.

Dallas, Texas, United States

Site Status RECRUITING

Houston Methodist Lung Transplant Center, 6550 Fannin St., SM1001

Houston, Texas, United States

Site Status RECRUITING

UT Health San Antonio 7703 Floyd Curl Drive, MSC: 7858

San Antonio, Texas, United States

Site Status RECRUITING

The Alfred Hospital, Monash University

Melbourne, , Australia

Site Status RECRUITING

Department of Thoracic Surgery, Medical University of Vienna

Vienna, , Austria

Site Status NOT_YET_RECRUITING

Department of Medicine, University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

Alberta Transplant Applied Genomics Centre, University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Motol University Hospital, V Uvalu 84

Prague, , Czechia

Site Status RECRUITING

Charles University/Hospital Motol

Prague, , Czechia

Site Status RECRUITING

Countries

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United States Australia Austria Canada Czechia

Central Contacts

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Konrad S Famulski, PhD DSc

Role: CONTACT

1 780 782 9463

Robert Polakowski, PhD

Role: CONTACT

1 780 492 5091

Facility Contacts

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Chanti F Smith

Role: primary

Duncan Lewis, BS, CCRP

Role: primary

Gabriel Parker, MA

Role: primary

Erin Sartoris, RN

Role: primary

Cheryl Pai

Role: primary

Shreena Patel, MPH, LPN

Role: primary

Alan Koester

Role: primary

Felicia Padilla

Role: primary

214-820-1771

Irina L Timofte, MD

Role: primary

Darrel W Cleere

Role: primary

Renee Walruff, BS

Role: primary

Glen Westall, MD PhD

Role: primary

+61 3 9076 2405

Dagmar Liebhart

Role: primary

Kieran Halloran, MD MSC

Role: primary

1 780 492 2691

Konrad S Famulski, PhD DSc

Role: primary

1 7807829463

Robert Polakowski, PhD

Role: backup

1 7804925091

Shaf Keshavjee, MD MSc

Role: primary

1 416-340-3863

Jolana Hertova

Role: primary

+420 775 216 790

Jan Havlin, MD

Role: primary

Other Identifiers

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Pro00048176

Identifier Type: -

Identifier Source: org_study_id

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