Diagnostic and Therapeutic Applications of Microarrays in Lung Transplantation
- Conditions
- Lung Transplant Rejection
- Registration Number
- NCT02812290
- Lead Sponsor
- University of Alberta
- Brief 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.
- Detailed 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 1032 TBBs and 600 3BMBs from 881 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 700
- All lung transplant recipients undergoing a biopsy as determined by their surgeon or physician.
- Patients who declined participation or unable to give informed consent.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Report the molecular diagnoses of the MMDx-TBB system two years Compare MMDx readings to standard-of-care TBB histology and clinical diagnosis of CLAD.
Report the molecular scores (probability) of lung transplant disease in a reference set of 600 transbronchial biopsies. two years Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction.
- Secondary Outcome Measures
Name Time Method Report the molecular diagnoses of the MMDx-3BMB system two years Compare MMDx-3BMB readings to MMDx-TBB readings and clinical diagnosis of CLAD
Report the molecular scores (probability) of lung transplant disease in a reference set of 600 mucosal endobronchial biopsies. two years Molecular classifier predicts antibody mediated and T cell mediated rejection, and chronic allograft dysfunction.
Report the molecular changes over time in medically indicated follow-up biopsies two years Predict and monitor response to anti-rejection treatment.
Trial Locations
- Locations (10)
The Alfred Hospital, Monash University
🇦🇺Melbourne, Australia
Alberta Transplant Applied Genomics Centre, University of Alberta
🇨🇦Edmonton, Alberta, Canada
University of Texas at San Antonio
🇺🇸San Antonio, Texas, United States
Department of Thoracic Surgery, Medical University of Vienna
🇦🇹Vienna, Austria
Division of Pulmonary and Critical Care, Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Department of Medicine, University of Alberta
🇨🇦Edmonton, Alberta, Canada
Thoracic Surgery Transplant Clinic
🇵🇱Szczecin, Poland
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
University Health Network, Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Charles University/Hospital Motol
🇨🇿Prague, Czechia