Precision Diagnosis and Care for Families With Pulmonary Fibrosis in Ireland

NCT ID: NCT06702228

Last Updated: 2024-11-22

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

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-09-28

Study Completion Date

2028-04-01

Brief Summary

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This study aims to improve the understanding of how genes and the environment can influence and cause pulmonary fibrosis. By identifying the presence of genes and other factors that can put people at risk of developing pulmonary fibrosis, the influence these factors have on the progression of the disease can be studied.

Interstitial lung disease (ILD) is the medical term given to a group of lung diseases affecting the same part of the lung, the interstitium, each with similar symptoms. In some of these diseases, inflammation leads to lung scarring, known as fibrosis. Idiopathic Pulmonary Fibrosis (IPF) is one of these diseases; it has a particular pattern on computed tomography (CT) scans. IPF is 'idiopathic' as it is not yet fully understood why it happens. It has a poor prognosis. The average survival time is three to five years after diagnosis. While new antifibrotic drugs offer hope of slowing disease progression, lung transplant is the only cure, and it comes with its significant risks.

Although it is not fully understood what causes IPF, it is known that genetic factors significantly increase the risk of developing the disease. Up to a quarter (25%) of people with IPF with a family history appear to have a causative genetic variant. Familial-pulmonary-fibrosis (FPF), the term for people with at least one relative with IPF, may have worse disease when compared to those without a family history. However, this needs more research. Patients with specific genes, telomere-related gene variants, appear to have a greater risk of developing blood disorders from medications given to suppress the body's immune system after a lung transplant.

Progressive pulmonary fibrosis is pulmonary fibrosis where there is irreversible worsening of the disease, worsening of lung function, respiratory symptoms and even early death. It is of growing importance regardless of the cause, whether it be idiopathic, familial or secondary to a connective tissue disease. ILD is increasingly recognised as a complication of connective tissue diseases. It is the leading cause of death in people with systemic sclerosis. The new antifibrotic drugs slow the progression of CTD-ILD. People with progressive pulmonary fibrosis who have a greater than 10% drop over one year in a measure of their lung function, called the forced vital capacity, benefit most from antifibrotic therapy. Early identification of people with progressive disease would allow the commencement of treatment quicker. At-home spirometry may be a way of identifying those who are worsening early.

This study hypothesises that by improving knowledge of factors that affect disease behaviour and progression and assessing tools for the early identification of progressive disease, such as at-home spirometry and CT scan pattern determination by deep-learning analysis, we can provide 'precision' diagnosis and treatment. It is hoped that this improved understanding will help reduce the clinical risk for people with pulmonary fibrosis and their families.

This study aims to recruit 300 patients: 100 with IPF, 100 with FPF, and 100 with CTD ILD. Each participant will be followed for one year.

This observational study aims to help answer a number of questions:

1. What genetic variants cause people to develop ILD, and which increase a person's risk of developing ILD are present in the study population?
2. How does pulmonary fibrosis behave in people who have a family history of IPF compared to those who do not and in people with CTD-ILD?
3. Are different types of pulmonary fibrosis more progressive than others i.e. Is pulmonary fibrosis in those with a family history of pulmonary fibrosis more progressive than in those who do not have a family history?
4. Is the disease in those with a genetic variant known to cause ILD worse than in those who don't have a gene?
5. Can at-home spirometry help identify people at risk of progressive disease early?
6. Can deep-learning analysis (AI) be used to find CT scan patterns to predict when pulmonary fibrosis will worsen?

Detailed Description

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Conditions

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Connective Tissue Diseases Interstitial Lung Disease Idiopathic Pulmonary Fibrosis Familial Idiopathic Pulmonary Fibrosis Pulmonary Fibrosis Pulmonary Fibrosis Interstitial

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Familial pulmonary fibrosis group

Patients meeting the study inclusion criteria with an multidisciplinary team (MDT) diagnosis of a fibrotic interstitial lung disease, reporting one or more relatives with a fibrotic form of ILD

Six minute walk test (6MWT)

Intervention Type DIAGNOSTIC_TEST

Assessment of exercise capacity by the carrying out of a 6MWT at 0, 6 and 12 months.

Computer-tomography of the thorax (CT Thorax)

Intervention Type DIAGNOSTIC_TEST

Radiological assessment via CT Thorax, preferably high-resolution CT thorax at baseline on entering the study and at one year. CT images will be collected on study end. CT images in all subjects will be evaluated by three readers blinded to any other interpretation and conforming to ATS-guidelines. Coded data from CT scans will be shared with our collaborator Professor Simon Walsh at Imperial College, London who will use computational methods to identify novel radiologic phenotypes linked to disease behaviour of our patient's fibrotic lung disease.

Quality of life questionnaires.

Intervention Type OTHER

Qality of life questionnaires including; modified Medical Research Council (mMRC) dyspnea scale, The King's Brief Interstitial Lung Disease Questionnaire (KBILD), The Leister Cough Questionnaire and the EQ-5D-3L questionnaire are measured at 0, 6 and 12 months

Genetic Testing

Intervention Type DIAGNOSTIC_TEST

10ml of serum will be collected for DNA extraction and analysed for causative and at risk genetic mutations

Spirometry

Intervention Type DIAGNOSTIC_TEST

We will carry out spirometry at baseline, 6 and 2 months including forced vital capacity and diffusing capacity of the lungs for carbon monoxide.

Serology

Intervention Type DIAGNOSTIC_TEST

Serology which may indicate an underlying diagnosis of ILD will be carried out on study entry. This will include a full blood count, renal profile, liver profile, C-reactive protein, creatine kinase, erythrocyte sedimentation rate, antinuclear antibodies, anticyclic citrullinated peptide antibodies, rheumatoid factor, an extended myositis antibody panel, sjögren's antibodies, scleroderma antibodies and a hypersensivity pneumonitis panel if clinically indicated.

PatientMPower Home Monitoring App

Intervention Type OTHER

Continuous at home monitoring of patients using home-based digital spirometry and pulse-oximetry with real-time feedback readings to patient and clinician. Smartphone app for patients, spirometer and pulse oximeter are connected to the app via Bluetooth. Patients are asked to take 2 readings per week.

Idiopathic pulmonary fibrosis group

Patients meeting the study inclusion criteria with an MDT diagnosis of IPF in accordance with consensus criteria, ATS, ERS, JRS, ALAT guidelines, without a family history of pulmonary fibrosis.

Six minute walk test (6MWT)

Intervention Type DIAGNOSTIC_TEST

Assessment of exercise capacity by the carrying out of a 6MWT at 0, 6 and 12 months.

Computer-tomography of the thorax (CT Thorax)

Intervention Type DIAGNOSTIC_TEST

Radiological assessment via CT Thorax, preferably high-resolution CT thorax at baseline on entering the study and at one year. CT images will be collected on study end. CT images in all subjects will be evaluated by three readers blinded to any other interpretation and conforming to ATS-guidelines. Coded data from CT scans will be shared with our collaborator Professor Simon Walsh at Imperial College, London who will use computational methods to identify novel radiologic phenotypes linked to disease behaviour of our patient's fibrotic lung disease.

Quality of life questionnaires.

Intervention Type OTHER

Qality of life questionnaires including; modified Medical Research Council (mMRC) dyspnea scale, The King's Brief Interstitial Lung Disease Questionnaire (KBILD), The Leister Cough Questionnaire and the EQ-5D-3L questionnaire are measured at 0, 6 and 12 months

Genetic Testing

Intervention Type DIAGNOSTIC_TEST

10ml of serum will be collected for DNA extraction and analysed for causative and at risk genetic mutations

Spirometry

Intervention Type DIAGNOSTIC_TEST

We will carry out spirometry at baseline, 6 and 2 months including forced vital capacity and diffusing capacity of the lungs for carbon monoxide.

Serology

Intervention Type DIAGNOSTIC_TEST

Serology which may indicate an underlying diagnosis of ILD will be carried out on study entry. This will include a full blood count, renal profile, liver profile, C-reactive protein, creatine kinase, erythrocyte sedimentation rate, antinuclear antibodies, anticyclic citrullinated peptide antibodies, rheumatoid factor, an extended myositis antibody panel, sjögren's antibodies, scleroderma antibodies and a hypersensivity pneumonitis panel if clinically indicated.

PatientMPower Home Monitoring App

Intervention Type OTHER

Continuous at home monitoring of patients using home-based digital spirometry and pulse-oximetry with real-time feedback readings to patient and clinician. Smartphone app for patients, spirometer and pulse oximeter are connected to the app via Bluetooth. Patients are asked to take 2 readings per week.

Connective tissue disease related interstitial lung disease group

Patients meeting the study inclusion criteria who meet the American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis, scleroderma, Sjogren's syndrome, idiopathic inflammatory myopathy and systemic lupus erythematosus criteria

Six minute walk test (6MWT)

Intervention Type DIAGNOSTIC_TEST

Assessment of exercise capacity by the carrying out of a 6MWT at 0, 6 and 12 months.

Computer-tomography of the thorax (CT Thorax)

Intervention Type DIAGNOSTIC_TEST

Radiological assessment via CT Thorax, preferably high-resolution CT thorax at baseline on entering the study and at one year. CT images will be collected on study end. CT images in all subjects will be evaluated by three readers blinded to any other interpretation and conforming to ATS-guidelines. Coded data from CT scans will be shared with our collaborator Professor Simon Walsh at Imperial College, London who will use computational methods to identify novel radiologic phenotypes linked to disease behaviour of our patient's fibrotic lung disease.

Quality of life questionnaires.

Intervention Type OTHER

Qality of life questionnaires including; modified Medical Research Council (mMRC) dyspnea scale, The King's Brief Interstitial Lung Disease Questionnaire (KBILD), The Leister Cough Questionnaire and the EQ-5D-3L questionnaire are measured at 0, 6 and 12 months

Genetic Testing

Intervention Type DIAGNOSTIC_TEST

10ml of serum will be collected for DNA extraction and analysed for causative and at risk genetic mutations

Spirometry

Intervention Type DIAGNOSTIC_TEST

We will carry out spirometry at baseline, 6 and 2 months including forced vital capacity and diffusing capacity of the lungs for carbon monoxide.

Serology

Intervention Type DIAGNOSTIC_TEST

Serology which may indicate an underlying diagnosis of ILD will be carried out on study entry. This will include a full blood count, renal profile, liver profile, C-reactive protein, creatine kinase, erythrocyte sedimentation rate, antinuclear antibodies, anticyclic citrullinated peptide antibodies, rheumatoid factor, an extended myositis antibody panel, sjögren's antibodies, scleroderma antibodies and a hypersensivity pneumonitis panel if clinically indicated.

Other Quality of Life Questionnaires

Intervention Type OTHER

Patient Global Assessment and Clinician Global Assessment scores completed at 0, 6 and 12 months

PatientMPower Home Monitoring App

Intervention Type OTHER

Continuous at home monitoring of patients using home-based digital spirometry and pulse-oximetry with real-time feedback readings to patient and clinician. Smartphone app for patients, spirometer and pulse oximeter are connected to the app via Bluetooth. Patients are asked to take 2 readings per week.

Interventions

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Six minute walk test (6MWT)

Assessment of exercise capacity by the carrying out of a 6MWT at 0, 6 and 12 months.

Intervention Type DIAGNOSTIC_TEST

Computer-tomography of the thorax (CT Thorax)

Radiological assessment via CT Thorax, preferably high-resolution CT thorax at baseline on entering the study and at one year. CT images will be collected on study end. CT images in all subjects will be evaluated by three readers blinded to any other interpretation and conforming to ATS-guidelines. Coded data from CT scans will be shared with our collaborator Professor Simon Walsh at Imperial College, London who will use computational methods to identify novel radiologic phenotypes linked to disease behaviour of our patient's fibrotic lung disease.

Intervention Type DIAGNOSTIC_TEST

Quality of life questionnaires.

Qality of life questionnaires including; modified Medical Research Council (mMRC) dyspnea scale, The King's Brief Interstitial Lung Disease Questionnaire (KBILD), The Leister Cough Questionnaire and the EQ-5D-3L questionnaire are measured at 0, 6 and 12 months

Intervention Type OTHER

Genetic Testing

10ml of serum will be collected for DNA extraction and analysed for causative and at risk genetic mutations

Intervention Type DIAGNOSTIC_TEST

Spirometry

We will carry out spirometry at baseline, 6 and 2 months including forced vital capacity and diffusing capacity of the lungs for carbon monoxide.

Intervention Type DIAGNOSTIC_TEST

Serology

Serology which may indicate an underlying diagnosis of ILD will be carried out on study entry. This will include a full blood count, renal profile, liver profile, C-reactive protein, creatine kinase, erythrocyte sedimentation rate, antinuclear antibodies, anticyclic citrullinated peptide antibodies, rheumatoid factor, an extended myositis antibody panel, sjögren's antibodies, scleroderma antibodies and a hypersensivity pneumonitis panel if clinically indicated.

Intervention Type DIAGNOSTIC_TEST

Other Quality of Life Questionnaires

Patient Global Assessment and Clinician Global Assessment scores completed at 0, 6 and 12 months

Intervention Type OTHER

PatientMPower Home Monitoring App

Continuous at home monitoring of patients using home-based digital spirometry and pulse-oximetry with real-time feedback readings to patient and clinician. Smartphone app for patients, spirometer and pulse oximeter are connected to the app via Bluetooth. Patients are asked to take 2 readings per week.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Able and willing to give written informed consent.
* An MDT diagnosis of fibrotic ILD which fall into one of the following three catagories;

1. Have a multidisciplinary team (MDT) diagnosis of a fibrotic interstitial lung disease, reporting one or more relatives with a fibrotic form of ILD
2. Have a MDT diagnosis of IPF in accordance with consensus criteria, ATS, ERS, JRS, ALAT guidelines without a family history of pulmonary fibrosis.
3. Meet the American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis, scleroderma, Sjogren's syndrome, idiopathic inflammatory myopathy and systemic lupus erythematosus.

Exclusion Criteria

* Currently participating in an interventional clinic trial.
* Change in clinical phenotype from initial radiological diagnosis to screening.
* Acute or chronic hypersensitivity pneumonitis with consensus criteria (appropriate exposure history, radiological features ± avian and fungal precipitins).
* Asbestosis (appropriate occupational history and radiological evidence of asbestos exposure)
* Life expectancy for any disease, including ILD \<12 months (investigator assessment)
* Major extrapulmonary physiological restriction (e.g. chest wall abnormality, large pleural effusion)
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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patientMpower Ltd.

INDUSTRY

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role collaborator

Royal College of Surgeons, Ireland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Killian Hurley

Role: PRINCIPAL_INVESTIGATOR

RCSI

Locations

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Beaumont Hospital

Dublin, , Ireland

Site Status RECRUITING

Countries

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Ireland

Central Contacts

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Killian Hurley

Role: CONTACT

+35318093000 ext. 3058

References

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Peljto AL, Blumhagen RZ, Walts AD, Cardwell J, Powers J, Corte TJ, Dickinson JL, Glaspole I, Moodley YP, Vasakova MK, Bendstrup E, Davidsen JR, Borie R, Crestani B, Dieude P, Bonella F, Costabel U, Gudmundsson G, Donnelly SC, Egan J, Henry MT, Keane MP, Kennedy MP, McCarthy C, McElroy AN, Olaniyi JA, O'Reilly KMA, Richeldi L, Leone PM, Poletti V, Puppo F, Tomassetti S, Luzzi V, Kokturk N, Mogulkoc N, Fiddler CA, Hirani N, Jenkins RG, Maher TM, Molyneaux PL, Parfrey H, Braybrooke R, Blackwell TS, Jackson PD, Nathan SD, Porteous MK, Brown KK, Christie JD, Collard HR, Eickelberg O, Foster EE, Gibson KF, Glassberg M, Kass DJ, Kropski JA, Lederer D, Linderholm AL, Loyd J, Mathai SK, Montesi SB, Noth I, Oldham JM, Palmisciano AJ, Reichner CA, Rojas M, Roman J, Schluger N, Shea BS, Swigris JJ, Wolters PJ, Zhang Y, Prele CMA, Enghelmayer JI, Otaola M, Ryerson CJ, Salinas M, Sterclova M, Gebremariam TH, Myllarniemi M, Carbone RG, Furusawa H, Hirose M, Inoue Y, Miyazaki Y, Ohta K, Ohta S, Okamoto T, Kim DS, Pardo A, Selman M, Aranda AU, Park MS, Park JS, Song JW, Molina-Molina M, Planas-Cerezales L, Westergren-Thorsson G, Smith AV, Manichaikul AW, Kim JS, Rich SS, Oelsner EC, Barr RG, Rotter JI, Dupuis J, O'Connor G, Vasan RS, Cho MH, Silverman EK, Schwarz MI, Steele MP, Lee JS, Yang IV, Fingerlin TE, Schwartz DA. Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants. Am J Respir Crit Care Med. 2023 May 1;207(9):1194-1202. doi: 10.1164/rccm.202207-1331OC.

Reference Type BACKGROUND
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Other Identifiers

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PRECISE-PF

Identifier Type: -

Identifier Source: org_study_id

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