Diagnostic and Therapeutic Applications of Microarrays in Lung Transplantation

NCT ID: NCT02812290

Last Updated: 2025-11-20

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

700 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-05-31

Study Completion Date

2026-12-31

Brief Summary

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Objective: To evaluate the potential impact of molecular phenotyping of transbronchial biopsies in lung transplant recipients with allograft dysfunction, and the potential for developing a safer endobronchial mucosal biopsy format.

Detailed Description

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The current standard for biopsy-based diagnoses of dysfunction of lung transplants is the International Society of Heart and Lung Transplantation (ISHLT) classification applied to transbronchial biopsies, which represents an arbitrary international consensus. Recent data-driven approaches using molecular and conventional technologies indicate that this system produces frequently incorrect diagnoses with potential harm to patients due to inappropriate treatment. especially in relationship to the correct diagnosis of chronic lung allograft dysfunction is a pressing need. To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype. The MMDx, developed first in kidney transplant biopsies with thoroughly established phenotypes, will now be adapted to lung transplant transbronchial biopsies (TBBs). Microarray analysis of lung allograft biopsy specimens will be compared to conventional allograft phenotyping, including clinical, physiologic, radiographic and histological assessment. The present study will use the MMDx™ system to assess and report TBBs, and validate and refine this system in 300 unselected prospectively collected lung TBBs. A subset of the study will examine the third bifurcation mucosal endobronchial biopsies (3BMBs) paired with TBBs from 50 patients to see if the safer 3BMBs can substitute for the TBB to be used by MMDx™. Due to a considerable interest and support from participating Centers, the study is further extended and collected 1032 TBBs and 602 3BMBs from 849 patients. This this is the extension of the INTERLUNG study - INTERLUNGEX.

Conditions

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Lung Transplant Rejection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Lung transplant biopsy bites.

In the second phase of the study, two biopsy bites from the same patient will be collected to assess tissue sampling variability.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* All lung transplant recipients undergoing a biopsy as determined by their surgeon or physician.

Exclusion Criteria

* Patients who declined participation or unable to give informed consent.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Alberta

OTHER

Sponsor Role lead

Responsible Party

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Philip Halloran

Distinguished Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Philip F Halloran, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Faculty of Medicine and Dentistry, 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

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status COMPLETED

Division of Pulmonary and Critical Care, Washington University School of Medicine

St Louis, Missouri, United States

Site Status COMPLETED

University of Texas at San Antonio

San Antonio, Texas, United States

Site Status COMPLETED

The Alfred Hospital, Monash University

Melbourne, , Australia

Site Status COMPLETED

Department of Thoracic Surgery, Medical University of Vienna

Vienna, , Austria

Site Status COMPLETED

Alberta Transplant Applied Genomics Centre, University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

Department of Medicine, University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

University Health Network, Toronto General Hospital

Toronto, Ontario, Canada

Site Status COMPLETED

Charles University/Hospital Motol

Prague, , Czechia

Site Status RECRUITING

Thoracic Surgery Transplant Clinic

Szczecin, , Poland

Site Status COMPLETED

Countries

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United States Australia Austria Canada Czechia Poland

Central Contacts

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Konrad S Famulski, PhD

Role: CONTACT

1 780 492 1725

Robert Polakowski, PhD

Role: CONTACT

1 780 492 5091

Facility Contacts

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Chanti F Smith

Role: primary

214-820-1771

Konrad S Famulski, PhD

Role: primary

1 780 492 1725

Kieran Halloran, MD

Role: primary

1 780 492 2691

Jan Havlin, Dr

Role: primary

References

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Madill-Thomsen KS, Halloran PF. Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope(R) Diagnostic System (MMDx). Clin Sci (Lond). 2024 Jun 5;138(11):663-685. doi: 10.1042/CS20220530.

Reference Type BACKGROUND
PMID: 38819301 (View on PubMed)

Halloran KM, Parkes MD, Chang J, Timofte IL, Snell GI, Westall GP, Hachem R, Kreisel D, Trulock E, Roux A, Juvet S, Keshavjee S, Jaksch P, Klepetko W, Halloran PF. Molecular assessment of rejection and injury in lung transplant biopsies. J Heart Lung Transplant. 2019 May;38(5):504-513. doi: 10.1016/j.healun.2019.01.1317. Epub 2019 Feb 6.

Reference Type RESULT
PMID: 30773443 (View on PubMed)

Halloran K, Parkes MD, Timofte I, Snell G, Westall G, Havlin J, Lischke R, Hachem R, Kreisel D, Levine D, Kubisa B, Piotrowska M, Juvet S, Keshavjee S, Jaksch P, Klepetko W, Hirji A, Weinkauf J, Halloran PF. Molecular T-cell-mediated rejection in transbronchial and mucosal lung transplant biopsies is associated with future risk of graft loss. J Heart Lung Transplant. 2020 Dec;39(12):1327-1337. doi: 10.1016/j.healun.2020.08.013. Epub 2020 Aug 26.

Reference Type RESULT
PMID: 32943286 (View on PubMed)

Halloran K, Parkes MD, Timofte IL, Snell GI, Westall GP, Hachem R, Kreisel D, Levine D, Juvet S, Keshavjee S, Jaksch P, Klepetko W, Hirji A, Weinkauf J, Halloran PF. Molecular phenotyping of rejection-related changes in mucosal biopsies from lung transplants. Am J Transplant. 2020 Apr;20(4):954-966. doi: 10.1111/ajt.15685. Epub 2019 Dec 1.

Reference Type RESULT
PMID: 31679176 (View on PubMed)

Parkes MD, Halloran K, Hirji A, Pon S, Weinkauf J, Timofte IL, Snell GI, Westall GP, Havlin J, Lischke R, Zajacova A, Hachem R, Kreisel D, Levine D, Kubisa B, Piotrowska M, Juvet S, Keshavjee S, Jaksch P, Klepetko W, Halloran PF. Transcripts associated with chronic lung allograft dysfunction in transbronchial biopsies of lung transplants. Am J Transplant. 2022 Apr;22(4):1054-1072. doi: 10.1111/ajt.16895. Epub 2021 Dec 16.

Reference Type RESULT
PMID: 34850543 (View on PubMed)

Halloran K, Mackova M, Parkes MD, Hirji A, Weinkauf J, Timofte IL, Snell GI, Westall GP, Lischke R, Zajacova A, Havlin J, Hachem R, Kreisel D, Levine D, Kubisa B, Piotrowska M, Juvet S, Keshavjee S, Jaksch P, Klepetko W, Halloran PF. The molecular features of chronic lung allograft dysfunction in lung transplant airway mucosa. J Heart Lung Transplant. 2022 Dec;41(12):1689-1699. doi: 10.1016/j.healun.2022.08.014. Epub 2022 Aug 27.

Reference Type RESULT
PMID: 36163162 (View on PubMed)

Gauthier PT, Mackova M, Hirji A, Weinkauf J, Timofte IL, Snell GI, Westall GP, Havlin J, Lischke R, Zajacova A, Simonek J, Hachem R, Kreisel D, Levine D, Kubisa B, Piotrowska M, Juvet S, Keshavjee S, Jaksch P, Klepetko W, Halloran K, Halloran PF. Defining a natural killer cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies. Am J Transplant. 2023 Dec;23(12):1922-1938. doi: 10.1016/j.ajt.2023.06.003. Epub 2023 Jun 7.

Reference Type RESULT
PMID: 37295720 (View on PubMed)

Mackova M, Gauthier P, Chang J, Hirji A, Weinkauf J, Juvet S, Keshavjee S, Havlin J, Lischke R, Zajacova A, Snell G, Westall G, Halloran PF, Halloran K. Molecular biopsy features associated with baseline lung allograft dysfunction in a multicenter international cohort. J Heart Lung Transplant. 2025 Nov 14:S1053-2498(25)02394-0. doi: 10.1016/j.healun.2025.11.005. Online ahead of print.

Reference Type RESULT
PMID: 41242356 (View on PubMed)

Halloran PF. Integrating molecular and histologic interpretation of transplant biopsies. Clin Transplant. 2021 Apr;35(4):e14244. doi: 10.1111/ctr.14244. Epub 2021 Feb 17. No abstract available.

Reference Type DERIVED
PMID: 33595110 (View on PubMed)

Other Identifiers

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ATAGC 03

Identifier Type: -

Identifier Source: org_study_id

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