Optimising Screening for Early Disease Detection in Familial Pulmonary Fibrosis (FLORIS)

In this study the prognostic value of the current screening parameters for familial pulmonary fibrosis (FPF) will be investigated by looking at the screenings of 200 first-degree relatives of patients with FPF.

Also insight in the natural history of early FPF, and the necessary interval between screenings visits will be investigated.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Fibrosis Idiopathic Familial

Detailed Description

Familial pulmonary fibrosis (FPF) is a fatal lung disease that is often not diagnosed until a significant portion of the lung function is lost. Median survival after diagnosis is 3 to 5 years. As treatment can only slow down lung function decline, early disease detection is essential to provide timely therapeutic support. As first-degree relatives of patients with FPF are at high risk of developing pulmonary fibrosis as well, a screening protocol has been put in place. However, the value of current screening parameters to detect early asymptomatic disease as well as the optimal interval between screening appointments are unknown. A prospective study into the prognostic value of these screening markers in the target population and the appropriate clinical setting is needed to develop an evidence-based screening protocol. There will be an emphasis on easily operable parameters that may allow for redirection of (part of the) screening activities to the general practice in the future.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Jan Grutters, Prof.; Phone Number: +31883201453; Email: j.grutters@antoniusziekenhuis.nl
• Study Contact Backup: Name: Martijn Maus, MD; Phone Number: +31883201467; Email: m.maus@antoniusziekenhuis.nl

Study Locations

• Netherlands
  • Nieuwegein, Netherlands, 3435CM
    • Recruiting
    • St Antonius Hospital
    • Contact: Jan Grutters, Prof.; Phone Number: +31883201453; Email: j.grutters@antoniusziekenhuis.nl
    • Contact: Martijn Maus, MD; Phone Number: +31883201467; Email: m.maus@antoniusziekenhuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Asymptomatic first-degree relatives of patients with FPF are invited to enroll.

Description

Inclusion Criteria:

• Asymptomatic first-degree relative of patients with familial pulmonary fibrosis (FPF)

Exclusion Criteria:

• A previous diagnosis of interstitial lung disease (ILD)
• Minors (aged <18 years)
• Pregnant

Note: woman who are pregnant at the start of the study or at the time of the HRCT are not allowed to participate. If a participant gets pregnant at a later stage during the study, she will not be excluded from the study. To be able to account for a potential effect of pregnancy during data analysis, female participants can be asked if they are pregnant at every visit.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics of participants	Difference in age, sex, body weight, smoking history and comorbidities between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Forced Vital Capacity (FVC)	Difference in forced vital capacity (FVC) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc)	Difference in haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Total lung capacity (TLC)	Difference in total lung capacity (TLC) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Biomarker levels	Difference in Krebs von den Lungen 6 (KL6), chemokine (C-C motif) ligand 18 (CCL18), surfactant protein-D (SP-D), matrix metalloproteinase 7 (MMP7) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Oxygen saturation in 6-minute walk test (6MWT)	Difference in oxygen saturation (rest in %), oxygen saturation (after 6MWT in %), oxygen saturation (nadir in %) and oxygen saturation (difference between rest and nadir in %) (all continuous variables) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Distance (meters) in 6-minute walk test (6MWT)	Difference in distance covered (in meters) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
MUC5B genotype	Difference in MUC5B genotype (all discrete variables) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Patient reported cough score	Difference in visual analogue scale (VAS) for cough (scores between 0-100, with 100 being the worst) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Patient reported dyspnea score	Difference in medical research council (MRC) (scores between 0-5, with 5 being the worst) between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Clubbing	Difference in presence of digital clubbing between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline
Crackles	Difference in inspiratory crackles during lung auscultation between the group with ILD changes and the group without ILD changes present on enrollment HRCT	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Vital Capacity (FVC)	Difference in forced vital capacity (FVC) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc)	Difference in haemoglobulin-corrected carbon monoxide diffusing capacity (DLCOc) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Total lung capacity (TLC)	Difference in total lung capacity (TLC) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Biomarker levels	Difference in KL6, CCL18, SP-D and MMP7 over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Genotype	Difference in MUC5B genotype over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Oxygen saturation in 6-minute walk test (6MWT)	Difference in oxygen saturation (rest in %), oxygen saturation (after 6MWT in %), oxygen saturation (nadir in %) and oxygen saturation (difference between rest and nadir in %) (all continuous variables) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Distance (meters) in 6-minute walk test (6MWT)	Difference in distance covered (in meters) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Patient reported cough score	Difference in visual analogue scale (VAS) for cough (scores between 0-100, with 100 being the worst) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Patient reported dyspnea score	Difference in medical research council (MRC) (scores between 0-5, with 5 being the worst) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Digital clubbing	Difference in presence of digital clubbing over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Crackles	Difference in inspiratory crackles during lung auscultation over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Patient reported fatigue	Difference in fatigue assessment scale (FAS) (scores range from 10-50, with 50 being the worst) over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years
Patient reported health status	Difference in EuroQol 5D-5L (EQ-5D-5L) (comprises of a score in five levels, level 1-5 with 5 being the worst, and a visual analoque scale ranging from 0-100 with 100 being the best) and the over the course of 2 years in the subjects with presence of ILD changes on enrollment HRCT and also between the group with ILD changes and the group without ILD changes present on enrollment HRCT	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relatedness	In case multiple members of the same family are included in the study	Baseline
Blood count	Blood count (Consisting of; hemoglobin (mmol/l), erythrocytes (x10^12/l), mean corpuscular volume (fl), red cell distribution width (%), thrombocytes (x10^9/l), leukocytes (x10^9/l)) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between bloodcount in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT	2 years
Creatinin	creatinin (umol/l) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between creatinin in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT	2 years
Liver function tests	Liver function tests (consisting of: ASAT (U/l), ALAT (U/l), alkaline phosphatase (U/l), Gamma-glutamyl transpeptidase (U/l)) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between these liver function tests in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT	2 years
Total bilirubin	Total bilirubin (umol/l) as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between total bilirubin in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT	2 years
Additional blood based markers	Additional blood based markers as an exploratory measurement in the subjects with presence of ILD changes on enrollment HRCT and the difference between these blood based markers in the subjects with presence of ILD changes on enrollment HRCT and the group without ILD changes present on enrollment HRCT	2 years

Collaborators and Investigators

• Sponsor: St. Antonius Hospital
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development; Boeringer Ingelheim

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2021
• Primary Completion (Anticipated): June 16, 2025
• Study Completion (Anticipated): September 1, 2025

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: May 4, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Screening; Familial; Asymptomatic; Pulmonary Fibrosis; Family members; First-degree
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: NL75303.100.20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data of patients is coded

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No