Early Recognition of Progressive Lung Fibrosis in Systemic Rheumatic Diseases

NCT07541638 | Recruiting

• 1 other identifier: 6923
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Connective tissue diseases (CTDs) cover a broad range of systemic rheumatic disorders characterized by abnormal immune activation, chronic inflammatory response, and fibrosis of internal organs. The most prevalent is interstitial lung disease (ILD), a severe pulmonary complication seen in 10 to 50% of CTDs and a major determinant of disability and death. Prevalence and clinical course of CTD-ILDs vary widely and seem to be independent of treatment. Current screening and prognosis prediction strategies based on clinical variables and auto-antibodies are inadequate, and disease biomarkers are lacking. The research project aims to identify biomarkers of ILD involvement in CTD patients by characterizing the proteome and transcriptome of extracellular vesicles (EVs) isolated from serum. This will be integrated with high-resolution computed tomography (HRCT) using artificial intelligence (AI)-based imaging assessment. These novel biomarkers are expected to address some current limitations of standard laboratory biomarkers and conventional HRCT imaging. The investigator will involve a total of 200 CTD patients divided into two equal groups: those with ILD and those without. Serum EVs will be extracted from patient sera and characterized based on proteome and transcriptome content using mass spectrometry analysis and next-generation RNA-sequencing. The investigator will compare CTD patients with and without ILD, and progressive and non-progressive ILD patients according to OMERACT (Outcome Measures in Rheumatology) initiative criteria during a 12-month follow-up. HRCT features analyzed by a commercially available deep learning AI software will also be compared among CTD-ILD patients based on the occurrence of progression during follow-up. An advanced approach combining EVs analysis in serum and AI algorithms of HRCT images, and functional fibrosis assessment in vivo, could enhance our understanding of CTD-ILDs pathogenesis. The proposal aims to investigate for the first time the EVs proteomic and transcriptomic profile in serum of patients with CTDs to identify possible biomarkers of lung involvement. The integration of circulating EVs biomarkers with clinical phenotype and with advanced imaging technologies will provide novel diagnostic algorithms that early identify patients with lung involvement in CTD and patients at risk of pulmonary progression.

Conditions

Connective Tissue Diseases; Interstitial Lung Disease

Keywords

Connective Tissue Diseases; Interstitial lung disease; Extracellular Vesicles; Artificial Intelligence

Outcome Measures

Primary Outcomes (1)

• Serum EV characteristics according to ILD presence

  The co-primary endpoints will be the differences in serum EV single-protein quantity (expressed as fold change) and RNA expression (expressed as fold change) between CTD patients with and without ILD.

  Baseline

Secondary Outcomes (2)

• Serum EV characteristics according to ILD progression

  12 months

• AI-collected HRCT quantitative measures according to ILD progression

  12 months

Study Arms (2)

CTD patients with ILD

OTHER

A total of 200 consecutive CTD patients will be enrolled, divided into two equal groups of subjects with or without ILD. Based on the expected specific CTD and CTD-ILD prevalence in the general population, each group will include 60 patients with SSc, 50 patients with RA, 40 patients with SS, 20 patients with IIM, and 30 patients with UCTD, equally distributed between the two groups.

Other: No experimental intervention (medication or device)

CTD Patients without ILD

OTHER

CTD Patients without ILD A total of 200 consecutive CTD patients will be enrolled, divided into two equal groups of subjects with or without ILD. Based on the expected specific CTD and CTD-ILD prevalence in the general population, each group will include 60 patients with SSc, 50 patients with RA, 40 patients with SS, 20 patients with IIM, and 30 patients with UCTD, equally distributed between the two groups.

Other: No experimental intervention (medication or device)

Interventions

No experimental intervention (medication or device) OTHER

No experimental intervention (medication or device)

CTD Patients without ILD; CTD patients with ILD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male aged between 18 and 75 years.
• Signature of informed consent
• A clinical diagnosis of SSc, RA, SS, IIM, or UCTD that must adhere to internationally accepted classification criteria \[Aletha 2010, Van Der Hoogen 2013, Lundberg 2017, Shiboski 2016, Bottai 2017, Antunes 2019\].
• A high risk of ILD based on autoantibody profile, specifically: anti-Scl70+ or anti-RNAPIII+ for SSc, anti-CCP+ and/or RF+ for RA, anti-RoSSA+ and anti-LaSSB+ for primary SS, anti-synthetase+ for IIM. For UCTD patients, the enrollment criteria will be adapted to match those of Interstitial Pneumonia with Autoimmune Features (IPAF) \[Fernandes 2019\], with patients exhibiting one clinical feature of CTD and one serological domain criterion (e.g., ANA positive with nucleolar pattern, RF and anti-CCP positivity, anti-RoSSA and anti-LaSSB positivity, anti-Scl70 positivity) while not meeting the classification criteria for any other CTD.
• Evidence of ILD based on an HRCT documenting the presence of interstitial changes involving at least 10% of the parenchyma within the previous 6 weeks. An HRCT scan completely negative for ILD changes performed up to 6 weeks before enrollment will be evaluated for the group of CTD patients without ILD.
• Either naive to immunosuppressants or having been on a stable immunosuppressive regimen for the three months preceding blood collection for EV characterization. Treatment with rituximab must be not administered in the previous 24 weeks.

You may not qualify if:

• Current treatment with corticosteroids \>10 mg of prednisone.
• Poor peripheral venus access that would interfere with blood sampling

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Connective Tissue Diseases; Lung Diseases, Interstitial

Interventions

Dosage Forms

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Study Officials

• Silvia Laura Bosello

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Silvia Laura Bosello, MD PhD

CONTACT

+390630159650; silvialaura.bosello@policlinicogemelli.it

Giulia Wlderk, Biologist

CONTACT

+390630159650; giulia.wlderk@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Baseline cross sectional comparison with subsequent cohort longitudinal obeservation.

Study Record Dates

• First Submitted: March 26, 2026
• First Posted: April 21, 2026
• Study Start: November 7, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

IT (1)