Diagnostic and Therapeutic Applications of Microarrays in Lung Transplantation

Lung Transplant Rejection Clinical Trial

— INTERLUNG  

Official title:

Multi-Centric Observational Study to Analyze the Diagnostic Molecular Features in the Clinical Setting of Lung Allograft Biopsies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02812290
• Other study ID #: ATAGC 03
• Status: Recruiting
• Start date: May 2016
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: University of Alberta
• Contact: Konrad S Famulski, PhD
• Phone: 1 780 492 1725
• Email: konrad[@]ualberta.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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 1009 TBBs and 595 3BMBs from 874 patients. The investigators plan to collect more TBBS and 3BMBs at the conclusion of this study. This this is the extension of the INTERLUNG study - INTERLUNGEX.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700
• Est. completion date: June 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Transplant Rejection

Intervention

Procedure:
• 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.

Locations

Country	Name	City	State
Australia	The Alfred Hospital, Monash University	Melbourne
Austria	Department of Thoracic Surgery, Medical University of Vienna	Vienna
Canada	Alberta Transplant Applied Genomics Centre, University of Alberta	Edmonton	Alberta
Canada	Department of Medicine, University of Alberta	Edmonton	Alberta
Canada	University Health Network, Toronto General Hospital	Toronto	Ontario
Czechia	Charles University/Hospital Motol	Prague
Poland	Thoracic Surgery Transplant Clinic	Szczecin
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Division of Pulmonary and Critical Care, Washington University School of Medicine	Saint Louis	Missouri
United States	University of Texas at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czechia,  Poland, 

References & Publications (7)

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 — View Citation

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 feature — View Citation

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 transbro — View Citation

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 transpla — View Citation

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 Tran — View Citation

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. — View Citation

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 wi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Report the molecular scores (probability) of lung transplant disease in a reference set of 600 transbronchial biopsies.	Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction.	two years
Primary	Report the molecular diagnoses of the MMDx-TBB system	Compare MMDx readings to standard-of-care TBB histology and clinical diagnosis of CLAD.	two years
Secondary	Report the molecular scores (probability) of lung transplant disease in a reference set of 600 mucosal endobronchial biopsies.	Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction.	two years
Secondary	Report the molecular diagnoses of the MMDx-3BMB system	Compare MMDx-3BMB readings to MMDx-TBB readings and clinical diagnosis of CLAD	two years
Secondary	Report the molecular changes over time in medically indicated follow-up biopsies	Predict and monitor response to anti-rejection treatment.	two years