Precision Diagnosis and Care for Families With Pulmonary Fibrosis in Ireland

Sponsor
Royal College of Surgeons, Ireland
Study ID
NCT06702228
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - 85 Years
Healthy Volunteers
Not accepted

Interventions

  • Six minute walk test (6MWT) — 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) — 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. — 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 — DIAGNOSTIC_TEST
    10ml of serum will be collected for DNA extraction and analysed for causative and at risk genetic mutations
  • Spirometry — 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 — 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 — OTHER
    Patient Global Assessment and Clinician Global Assessment scores completed at 0, 6 and 12 months
  • PatientMPower Home Monitoring App — 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.

Study Details

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?

Key Dates

First listed
Nov 22, 2024
Start date
Sep 28, 2021
Status verified
Jun 2024
Primary completion
Jul 1, 2026
Completion
Apr 1, 2028

Study Design

Enrollment
300 participants (estimated)

Arms

  • Arm: 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
  • Arm: 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.
  • Arm: 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

Primary Outcome Measure

Determine if familial-pulmonary-fibrosis is more progressive than sporadic-IPF [ Time Frame: 12-months of entering the study ]

Central Contacts

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