Clinical trial NCT06644144: P4O2 ILD Extension
Official title: Early Identification of Progressive Pulmonary Fibrosis, Precision Medicine for More Oxygen - ILD Extension.
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: AbbVie
name: Boehringer Ingelheim
First posted: 2024-10-16
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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).

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.

Detailed description: Included participants will complete several study visits to collect clinical data and biological samples. Study visits will be performed at baseline, 3, 6, 12, 24, 36, 48 and 60 months, with a 2-month time window for follow-up visits. These time points are aligned with the standard clinical follow-up visits outlined in the ILD Care Path Protocol of Amsterdam UMC.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. FVC ≥45% predicted.
  2. FEV1/FVC ≥0.7.
  3. 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 \&gt; 18 years and \&lt; 80 years.
* Understanding of the Dutch or English language.

Exclusion Criteria:

* Combined pulmonary fibrosis and emphysema (CPFE) diagnosis
* Chronic obstructive lung disease (COPD) with an FEV1/FVC \&lt;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.

Primary outcomes:
measure: Inflammatory and fibrosis extent assessed by HRCT
timeFrame: 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))
measure: Pulmonary function tests (PFTs)- Spirometry volumes
timeFrame: It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))
measure: Pulmonary function tests (PFTs)- DLCO measurement
timeFrame: It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))
measure: Pulmonary function tests (PFTs)- Lungvolume measurement
timeFrame: It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))
measure: Biomarkers related to pulmonary fibrosis will be measured in plasma and serum
timeFrame: It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))
measure: Peripheral blood mononuclear cell (PBMC) populations in blood
timeFrame: 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)
measure: Exhaled breath analysis including volatile organic compounds
timeFrame: It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))
Secondary outcomes:
measure: Disease-relevant questionnaires: Exposure Questionnaire
timeFrame: Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))
measure: Disease-relevant questionnaires: KBILD questionnaire.
timeFrame: Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))
measure: Disease-relevant questionnaires: Modified Medical Research Council Dyspnea score
timeFrame: Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))
measure: Disease-relevant questionnaires: Visual analog scale (VAS)
timeFrame: Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))
measure: Disease-relevant questionnaires: Fatigue Severity Scale (FSS)
timeFrame: Questionnaires will be filled in at baseline, at 6, and 12 months, and every other year till end of follow-up (60months))
measure: Genomics analysis in blood.
timeFrame: Genomics are done once at baseline.
measure: Epigenomics analysis in blood.
timeFrame: Epigonomics are done at baseline and 1 year after inclusion.
measure: Transcriptome analysis in blood.
timeFrame: Transcriptome is performed at baseline, 6 months and 1 year after inclusion.
measure: Proteome analysis in bronchoalveolar lavage fluid
timeFrame: In Group 3, thirty participants will undergo bronchoalveolar lavage at baseline. Additional procedures may be performed during the follow-up period if clinically indicated and will be added to samples. .
measure: Microbiome analyses in stool and nasal swabs.
timeFrame: Once in first year
measure: Concentration of Biomarkers in Exhaled Particles (Collected via Impaction)
timeFrame: From moment of inclusion every year untill end of follow-up at 60 months.
measure: Identification of Compounds in Exhaled Particles via Mass Spectrometry (MS)
timeFrame: From moment of inclusion every year untill end of follow-up at 60 months.
measure: Separation and Quantification of Compounds in Exhaled Particles Using Liquid Chromatography (LC) and High-Performance Liquid Chromatography (HPLC)
timeFrame: From moment of inclusion every year untill end of follow-up at 60 months.
measure: Metabolome analyses in blood.
timeFrame: Twice in the first year of inclusion; baseline and at 6 months.
measure: Metabolome analyses in urine
timeFrame: Twice in the first year of inclusion; baseline and at 6 months.
measure: Personal exposure to environmental pollutants using the Ultrasonic Personal Air Sampler
timeFrame: Exposome will be measured twice in first year, dependant on season (for most patients at 6 and 1 year follow-up))
measure: External exposome analyses using Silicon wristbands
timeFrame: Exposome will be measured twice in first year, dependant on season (for most patients at 6 and 1 year follow-up))
measure: External exposome analyses using a Sniffer-bike
timeFrame: Exposome will be measured twice in first year, dependant on season (for most patients at 6 and 1 year follow-up))
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie VUmc
state: Noord-Holland
Study officials:
affiliation: Amsterdam UMC, locatie VUmc
name: Esther Nossent, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, locatie VUmc
name: Jan Willem Duitman, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, locatie VUmc
name: Anke-Hilse Maitland-van der Zee, PhD
role: PRINCIPAL_INVESTIGATOR
References: