Clinical Genetics and Screening for Idiopathic Pulmonary Fibrosis

Not yet recruiting

• Conditions: Idiopathic Pulmonary Fibrosis; Familial Pulmonary Fibrosis
• Interventions: Diagnostic Test: High resolution Computed Tomography (HRCT) scans of the Chest; Diagnostic Test: Pulmonary Function Testing (PFTs); Diagnostic Test: Digital lung sounds auscultation; Diagnostic Test: Laboratory Assessments; Genetic: DNA sequencing

• Registration Number: NCT06521125
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary

Background:

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of interstitial lung disease. Between 2% and 20% of patients with IPF have a family history of the disease, which is considered the strongest risk factor. Therefore, genetic testing has been increasingly considered as a potential tool to identify patients at risk of developing IPF.

According to some studies, genetic testing (particularly of MUC5B and TERT mutations) could be useful to rapidly identify unidentified and/or asymptomatic individuals (in families as well as in the general population) who have interstitial lung anomalies (ILA) that may indicate a initial stage of pulmonary fibrosis. Finding efficient screening methods and associated targeted treatments for IPF may be essential to improving the prognosis and quality of life of those suffering from this disease.

Objectives of the study:

The study involves two populations of study subjects:

* patients with FPF and sporadic IPF

* first-degree relatives of patients with FPF and sporadic IPF (biological relatives, not spouses)

The primary objective is to determine the prevalence rates of interstitial lung abnormalities in at-risk relatives of patient with IPF and FPF.

Study design:

Multicenter, cross-sectional study without drug and without device conducted in two major Italian tertiary referral hospitals.

The entire project is expected to last 24 months.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-16
• Study First Submitted QC: 2024-07-22
• Last Update Submitted: 2024-07-22
• Study First Posted: 2024-07-25
• Last Update Posted: 2024-07-25
• Study Start: 2024-09-01
• Primary Completion: 2026-09-01
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

1. patients aged ≥18 years when signing the informed consent
2. diagnosis of IPF based on 2022 ATS/ERS/JRS/ALAT Guidelines as confirmed by the investigator based on chest HRCT scan and if available surgical lung biopsy
3. diagnosis of FPF defined as the presence of fibrotic ILD in at least two members of the same biological family
4. at least one 1st degree relative >40 years of age.

Exclusion Criteria

1. patients with Interstitial Lung Diseases other than Idiopathic Pulmonary Fibrosis, including but not limited to patients with granulomatous lung disease, autoimmune/collagen vascular disease associated interstitial lung disease, and drug induced interstitial lung disease
2. unwilling or unable to sign informed consent

Criteria for FIRST DEGREE BIOLOGICAL RELATIVES:

Inclusion Criteria:

a. subjects aged ≥40 years

Exclusion Criteria:

1. previous diagnosis of IPF
2. a history of severe or poorly controlled anxiety, severe or poorly controlled depression according to the opinion of the investigators, suicidal ideation, or other psychiatric illness requiring hospitalization
3. unwilling or unable to sign informed consent 400 first-degree relatives of participating patients will be recruited

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with FPF and sporadic IPF	High resolution Computed Tomography (HRCT) scans of the Chest	-
Patients with FPF and sporadic IPF	Laboratory Assessments	-
First-degree relatives of patients with FPF and sporadic IPF	High resolution Computed Tomography (HRCT) scans of the Chest	-
First-degree relatives of patients with FPF and sporadic IPF	DNA sequencing	-
Patients with FPF and sporadic IPF	Digital lung sounds auscultation	-
Patients with FPF and sporadic IPF	DNA sequencing	-
First-degree relatives of patients with FPF and sporadic IPF	Pulmonary Function Testing (PFTs)	-
Patients with FPF and sporadic IPF	Pulmonary Function Testing (PFTs)	-
First-degree relatives of patients with FPF and sporadic IPF	Laboratory Assessments	-
First-degree relatives of patients with FPF and sporadic IPF	Digital lung sounds auscultation	-

Primary Outcome Measures

Name	Time	Method
Prevalence of ILA	At subject enrollment	The prevalence of ILA in first-degree relatives of patients with IPF, expressed as proportion of subjects with ILAs in the overall relatives population

Secondary Outcome Measures

Name	Time	Method
Association between ILA and genetic variants	At subject enrollment	To assess the risk of ILA in first-degree relatives of patients with FPF and sporadic IPF associated with clinically relevant mutations.; Univariate and multivariate logistic regression analysis will be utilized to assess the association between genetic variants and ILA