Molecular Diagnosis of Idiopathic Interstitial Pneumonias: a Prospective Study

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ClinicalTrials.gov Identifier: NCT03836417

Recruitment Status : Recruiting

First Posted : February 11, 2019

Last Update Posted : May 15, 2019

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Lawson Health Research Institute

Study Description

Brief Summary:

Molecular diagnosis of idiopathic interstitial pneumonias is an innovative way to potentially improve the diagnostic accuracy of surgical lung biopsies (SLBs), introducing molecular classifiers of idiopathic pulmonary fibrosis (IPF) vs. non-specific interstitial pneumonia (NSIP), the 2 main types of idiopathic interstitial pneumonias (IIPs).

The investigators hypothesize that pre-defined gene expression profiles previously identified on large lung explants can still be identified and reproducible on smaller, clinically available surgical lung biopsies (SLBs), and can be used to increase diagnostic accuracy during multi-disciplinary discussion.

The investigators also hypothesize that the expression level of individual, preselected genes that accurately differentiate IPF from NSIP on lung explants can be reproduced on SLBs.

The investigators will isolate RNA from SLBs obtained from patients with IIP and perform microarray analysis to verify the reproducibility of gene expression profiles on SLBs. Individual genes expression levels will be determined by RT-PCR.

The diagnosis will be determined by MDD and further validated by prospective follow-up of patients for a period of 3 years.

The investigators will assess the impact of molecular diagnostic techniques on interobserver agreement during multi-disciplinary discussion.

The investigators will prospectively follow the clinical course of patients after SLB for a period of 3 years to validate the diagnosis, and asses the diagnostic accuracy of molecular techniques.

Condition or disease	Intervention/treatment
Idiopathic Interstitial Pneumonia Idiopathic Pulmonary Fibrosis Nonspecific Interstitial Pneumonia	Diagnostic Test: Microarray analysis

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Study Design

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Study Type :	Observational
Estimated Enrollment :	100 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Molecular Diagnosis of Idiopathic Interstitial Pneumonias: a Prospective Study
Estimated Study Start Date :	May 6, 2019
Estimated Primary Completion Date :	February 28, 2022
Estimated Study Completion Date :	February 28, 2025

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Idiopathic pulmonary fibrosis

MedlinePlus related topics: Biopsy Genes and Gene Therapy Pneumonia

Genetic and Rare Diseases Information Center resources: Idiopathic Pulmonary Fibrosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Idiopathic interstitial pneumonias Patients with idiopathic interstitial pneumonias undergoing surgical lung biopsy	Diagnostic Test: Microarray analysis Microarray analysis to identify gene expression profiles that distinguish IPF from NSIP

Outcome Measures

Primary Outcome Measures :

Reproducibility of gene expression profiles on surgical lung biopsies [ Time Frame: February 2019-January 2022 ]
Proportion of patients (% of the total) with reproducible predefined gene expression profiles of either IPF or NSIP on surgical lung biopsy.

Secondary Outcome Measures :

Prognostic impact of gene expression profiles of IPF and NSIP [ Time Frame: February 2019-January 2025 ]
Hazard ratios of IPF and NSIP gene expression profiles (categorical variables) towards 3-year survival from the time of biopsy
Prognostic impact of selected genes expression levels [ Time Frame: February 2019-January 2025 ]
Hazard ratios of gene expression levels of 6 selected genes (continuous variables) towards 3-year survival from the time of biopsy.

Biospecimen Retention: Samples With DNA

Lung tissue biopsies

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

After ruling out known causes (connective tissue disease; occupational, environmental or domestic exposures; drug-induced lung toxicity) of interstitial lung disease, patients being referred for a surgical lung biopsy to clarify the diagnosis of IIP (IPF vs. NSIP) will be recruited in the study.

Criteria

Inclusion criteria:

Chronic interstitial lung disease not caused by connective tissue disease, drug-induced toxicity or environmental occupational or domestic exposures. These criteria equal to a diagnosis of idiopathic interstitial pneumonia (IIP).
High resolution chest CT scan not consistent with an idiopathic pulmonary fibrosis pattern, therefore requiring a surgical lung biopsy to clarify the exact diagnosis of IIP.
No contraindications to undergo a surgical lung biopsy (advanced disease stage; significant cardiac disease; significant obesity; or associated pulmonary hypertension).
Patient able to provide informed consent.

Exclusion criteria:

Chronic interstitial lung disease caused by connective tissue disease, drug-induced toxicity or environmental occupational or domestic exposures.
High resolution chest CT scan consistent with an idiopathic pulmonary fibrosis pattern, therefore not requiring a surgical lung biopsy.
Contraindications to undergo a surgical lung biopsy (advanced disease stage; significant cardiac disease; significant obesity; or associated pulmonary hypertension).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03836417

Contacts

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Contact: Marco Mura, MD, PhD	5196676744	marco.mura@lhsc.on.ca
Contact: Karishma Hosein, MSc	5196676744	karishma.hosein@lhsc.on.ca

Locations

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Canada, Ontario
London Health Science Centre	Recruiting
London, Ontario, Canada, N6A 5W9
Contact: Marco Mura, MD, PhD 5196676744 marco.mura@lhsc.on.ca
Contact: Karishma Hosein, MSc 5196676744 karishma.hosein@lhsc.on.ca

Sponsors and Collaborators

Lawson Health Research Institute

Investigators

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Principal Investigator:	Marco Mura, MD, PhD	Western University

More Information

Publications:

Cecchini MJ, Hosein K, Howlett CJ, Joseph M, Mura M. Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis. Respir Res. 2018 Aug 15;19(1):153. doi: 10.1186/s12931-018-0857-1.

Mura M, Anraku M, Yun Z, McRae K, Liu M, Waddell TK, Singer LG, Granton JT, Keshavjee S, de Perrot M. Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis. Chest. 2012 Mar;141(3):661-673. doi: 10.1378/chest.11-0449. Epub 2011 Aug 11.

Mura M, Porretta MA, Bargagli E, Sergiacomi G, Zompatori M, Sverzellati N, Taglieri A, Mezzasalma F, Rottoli P, Saltini C, Rogliani P. Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study. Eur Respir J. 2012 Jul;40(1):101-9. doi: 10.1183/09031936.00106011. Epub 2012 Jan 12.

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Responsible Party:	Lawson Health Research Institute
ClinicalTrials.gov Identifier:	NCT03836417 History of Changes
Other Study ID Numbers:	6156
First Posted:	February 11, 2019 Key Record Dates
Last Update Posted:	May 15, 2019
Last Verified:	May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Pneumonia Pulmonary Fibrosis Idiopathic Pulmonary Fibrosis Idiopathic Interstitial Pneumonias	Lung Diseases, Interstitial Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections

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