P4O2 ILD Extension

NCT06644144 | Recruiting DMC

• 2 other identifiers: 2023.0591NL84006.018.23
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to identify early biomarkers that can predict the development of progressive pulmonary fibrosis (PPF) in participants with interstitial lung diseases (ILDs). The participant population includes adults diagnosed with idiopathic pulmonary fibrosis (IPF), familial pulmonary fibrosis (FPF), other fibrotic ILDs, and interstitial lung abnormalities (ILA). The main questions it aims to answer are:

• What biomarkers and risk factors are linked to fibrosis progression or can predict rapid worsening and sudden flare-ups in IPF and FPF patients?
• What biomarkers and risk factors can predict the development of a PPF phenotype in different types of ILD?
• What biomarkers and risk factors can help identify ILA patients who may develop significant ILD?
• What biomarkers and risk factors can predict how well ILD patients will respond to treatment? Researchers will compare the outcomes between participants diagnosed with IPF/FPF, other fibrotic ILDs, and ILA to see if early detection biomarkers differ among these groups. Participants will:
• Undergo blood sampling.
• Perform lung function tests.
• Have CT scans.
• Perform breath analysis
• Participate in exposome and microbiome analyses.
• Complete questionnaires.
• A subgroup of participants will be offered bronchoscopy.

Conditions

Interstitial Lung Disease; Pulmonary Fibrosis; Interstitial Lung Fibrosis; IPF; Pulmonary Fibrosis, Idiopathic; Pulmonary Fibrosis Idiopathic Familial; Chronic Hypersensitivity Pneumonitis; Unclassifiable ILD; Idiopathic NSIP; CTD-ILD

Keywords

Interstitial Lung Disease; Interstitial Lung Abnormalities; Progressive Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (7)

• Inflammatory and fibrosis extent assessed by HRCT

  High-Resolution Computed Tomography (HRCT) is an advanced imaging technique used to obtain detailed images of the lungs and chest. Unlike standard CT scans, HRCT uses thin slices and special algorithms to produce high-resolution images that provide more precise visualization of lung structures, making it particularly useful for diagnosing and evaluating various lung conditions. The Inflammatory and Fibrosis extent will be analyzed by using artificial intelligence software.

  A baseline HRCT scan will be performed during screening. Following inclusion in the study, HRCT scans will be repeated annually, starting one year after the initial scan, and continuing each year until the end of follow-up (at 5 years))

• Pulmonary function tests (PFTs)- Spirometry volumes

  Pulmonary function tests (PFTs) are a group of tests that measure how well your lungs are working. These tests assess lung volume, capacity, rates of flow, and gas exchange. We will look at the following values: 1\. Spirometry Values * Forced Vital Capacity (FVC): The total amount of air exhaled after taking the deepest breath possible. * Forced Expiratory Volume in 1 Second (FEV1): The amount of air forcefully exhaled in one second.

  It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))

• Pulmonary function tests (PFTs)- DLCO measurement

  Pulmonary function tests (PFTs) are a group of tests that measure how well your lungs are working. These tests assess lung volume, capacity, rates of flow, and gas exchange. We will look at the Diffusion Capacity Tests (DLCO). DLCO: Measures how well oxygen and CO2 are exchanged between the lungs and the blood.

  It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))

• Pulmonary function tests (PFTs)- Lungvolume measurement

  Pulmonary function tests (PFTs) are a group of tests that measure how well your lungs are working. These tests assess lung volume, capacity, rates of flow, and gas exchange. We will look at the Lung Volumes and Capacities * Total Lung Capacity (TLC): The total volume of air in the lungs after taking the deepest breath. * Residual Volume (RV): The amount of air left in the lungs after a full exhalation. * Functional Residual Capacity (FRC): The amount of air remaining in the lungs after normal exhalation. * Inspiratory Capacity (IC): The maximum amount of air that can be inhaled after a normal exhalation.

  It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))

• Biomarkers related to pulmonary fibrosis will be measured in plasma and serum

  Blood will be taken from participants at the 8 different time points. A predefined panel of biomarkers related to pulmonary fibrosis will be measured in serum/plasma, urine, and, if available, bronchoalveolar lavage fluid. Biomarker levels will be correlated with the time to event (i.e., development of rapid progression or acute exacerbation) to identify biomarkers that predict rapid progression or acute exacerbation, as defined by the criteria by Raghu et al., (2022).

  It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))

• Peripheral blood mononuclear cell (PBMC) populations in blood

  Deep phenotyping of peripheral blood mononuclear cells (PBMCs) and, when available, BAL cells will be performed using flow cytometry, spectral flow, or cyTOF (cytometry by time of flight). A panel of surface and activation markers will define subsets of monocyte and lymphocyte populations. Data will be correlated to the time of the event.

  It will be measured Will be measured at baseline, at 3, 6 months, 12 months, and every other year till end of follow-up (60months)

• Exhaled breath analysis including volatile organic compounds

  Exhaled breath analysis involves measurements of volatile organic compounds (VOCs) using gas chromatography-mass spectrometry (GC-MS) and electronic sensor detection of exhaled breath compounds in a non-invasive manner (breathing into a device). For all participants, VOCs will be measured using GC-MS (in house GC mass spectrometer)..

  It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))

Secondary Outcomes (18)

• Disease-relevant questionnaires: Exposure Questionnaire

  Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))

• Disease-relevant questionnaires: KBILD questionnaire.

  Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))

• Disease-relevant questionnaires: Modified Medical Research Council Dyspnea score

  Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))

• Disease-relevant questionnaires: Visual analog scale (VAS)

  Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))

• Disease-relevant questionnaires: Fatigue Severity Scale (FSS)

  Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))

Study Arms (3)

Idiopathic Pulmonary Fibrosis/Familial Pulmonary Fibrosis

Other: No Interventions

fibrotic ILD

Patients with a diagnosis of: chronic Hypersensitivity Pneumonitis (cHP), unclassifiable ILD (uILD), idiopathic NSIP or CTD-ILD.

Other: No Interventions

Interstitial Lung Abnormalities

Other: No Interventions

Interventions

No Interventions OTHER

No intervention so not applicable.

Idiopathic Pulmonary Fibrosis/Familial Pulmonary Fibrosis; Interstitial Lung Abnormalities; fibrotic ILD

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The P4O2 ILD-extension is a non-interventional prospective observational cohort study that will include a minimum of 450 participants, divided intro three groups (1) 150 participants diagnosed with idiopathic pulmonary fibrosis (IPF) or familial pulmonary fibrosis (FPF); (2) 150 participants diagnosed with other fibrotic ILDs (fILD), including fibrotic hypersensitivity pneumonitis (fHP), idiopathic non-specific interstitial pneumonia (iNSIP), connective tissue disease (CTD)-ILD, and unclassifiable ILD (uILD); and (3) 150 participants diagnosed with interstitial lung abnormalities (ILA).

You may qualify if:

• Diagnosis of (1) idiopathic pulmonary fibrosis (IPF), familial pulmonary fibrosis (FPF), (2) other fibrotic ILDs (fILD), including fibrotic hypersensitivity pneumonitis (fHP), idiopathic non-specific interstitial pneumonia (iNSIP), connective tissue disease (CTD)-ILD, and unclassifiable ILD (uILD); or (3) interstitial lung abnormalities (ILA).
• Meeting all the following criteria during the screening period:
• FVC ≥45% predicted.
• FEV1/FVC ≥0.7.
• DLco corrected for Hb ≥40% predicted.
• Able to provide written informed consent as approved by the independent ethics committee.
• Able to undergo a CT scan and perform PFT.
• Age \> 18 years and \< 80 years.
• Understanding of the Dutch or English language.

You may not qualify if:

• Combined pulmonary fibrosis and emphysema (CPFE) diagnosis
• Chronic obstructive lung disease (COPD) with an FEV1/FVC \<70%.
• Uncontrolled severe asthma.
• Active malignancy, except for squamous cell carcinoma of the skin, low-risk breast cancer, and low-risk prostate cancer.
• Pregnancy or lactating.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• AbbVie: collaborator
• Boehringer Ingelheim: collaborator

Study Sites (1)

Amsterdam UMC, locatie VUmc

Amsterdam, North Holland, 1081 HV, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood, urine, feces, breath analysis, nasal brush, Bronchoalveolar lavage fluid, lung biopsy, Particles in Exhaled Air (PExA).

MeSH Terms

Conditions

Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Esther Nossent, MD

  Amsterdam UMC, locatie VUmc

  PRINCIPAL INVESTIGATOR

• Jan Willem Duitman, PhD

  Amsterdam UMC, locatie VUmc

  PRINCIPAL INVESTIGATOR

• Anke-Hilse Maitland-van der Zee, PhD

  Amsterdam UMC, locatie VUmc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan Willem Duitman, PhD

CONTACT

0205668753; j.w.duitman@amsterdamumc.nl

Iris Simons, MD

CONTACT

0205668753; i.simons@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Jan Willem Duitman

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: October 16, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2031
• Last Updated: April 3, 2025

Record last verified: 2025-03

Locations

NL (1)