Early Identification of Progressive Pulmonary Fibrosis, Precision Medicine for More Oxygen - ILD Extension.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Inflammatory and fibrosis extent assessed by HRCT
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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.
结局指标
主要结局
Inflammatory and fibrosis extent assessed by HRCT
时间窗: 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))
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.
Pulmonary function tests (PFTs)- DLCO measurement
时间窗: 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) 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.
Pulmonary function tests (PFTs)- Lungvolume measurement
时间窗: 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) 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.
Biomarkers related to pulmonary fibrosis will be measured in plasma and serum
时间窗: It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))
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).
Peripheral blood mononuclear cell (PBMC) populations in blood
时间窗: 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)
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.
Exhaled breath analysis including volatile organic compounds
时间窗: It will be measured at baseline, at 3, 6, and 12 months, and every other year till end of follow-up (60months))
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)..
Pulmonary function tests (PFTs)- Spirometry volumes
时间窗: 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) 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.
次要结局
- External exposome analyses using a Sniffer-bike(Exposome will be measured twice in first year, dependant on season (for most patients at 6 and 1 year follow-up)))
- 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)))
- Genomics analysis in blood.(Genomics are done once at baseline.)
- Epigenomics analysis in blood.(Epigonomics are done at baseline and 1 year after inclusion.)
- Transcriptome analysis in blood.(Transcriptome is performed at baseline, 6 months and 1 year after inclusion.)
- Proteome analysis in bronchoalveolar lavage fluid(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. .)
- Microbiome analyses in stool and nasal swabs.(Once in first year)
- Concentration of Biomarkers in Exhaled Particles (Collected via Impaction)(From moment of inclusion every year untill end of follow-up at 60 months.)
- Identification of Compounds in Exhaled Particles via Mass Spectrometry (MS)(From moment of inclusion every year untill end of follow-up at 60 months.)
- Separation and Quantification of Compounds in Exhaled Particles Using Liquid Chromatography (LC) and High-Performance Liquid Chromatography (HPLC)(From moment of inclusion every year untill end of follow-up at 60 months.)
- Metabolome analyses in blood.(Twice in the first year of inclusion; baseline and at 6 months.)
- Metabolome analyses in urine(Twice in the first year of inclusion; baseline and at 6 months.)
- Personal exposure to environmental pollutants using the Ultrasonic Personal Air Sampler(Exposome will be measured twice in first year, dependant on season (for most patients at 6 and 1 year follow-up)))
- External exposome analyses using Silicon wristbands(Exposome will be measured twice in first year, dependant on season (for most patients at 6 and 1 year follow-up)))
研究者
Jan Willem Duitman
Dr. Jan Willem Duitman
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)