Extracellular Vesicle Dynamics Predicting Vascular Complications and Treatment Response in Systemic Sclerosis

NCT07717060 | Not Yet Recruiting DMC

• 1 other identifier: 27513
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

Systemic sclerosis is a multisystem autoimmune disease characterized by vascular dysfunction, immune dysregulation, and progressive tissue fibrosis. Cardiopulmonary complications and peripheral vascular involvement are the principal causes of disability and mortality. Extracellular vesicles (EVs) have emerged as key mediators of paracrine intercellular communication. Preclinical studies further suggest that EVs mediate long-range inter-organ communication through the circulation. However, the inability to directly track EV trafficking in vivo in humans has limited the understanding of their contribution to systemic inter-organ communication. The investigators propose that systemic sclerosis provides a unique human model for investigating circulating EV-mediated inter-organ communication in a multisystem disease. The central hypothesis is that arteriovenous differences in the molecular and cellular characteristics of circulating EVs reflect their dynamic exchange between individual organs and the bloodstream, and that these differences are associated with disease severity. Comparison of EVs across the circulation, rather than relying exclusively on peripheral blood samples, enables a more direct assessment of organ-specific EV release and uptake. Characterizing EV dynamics along the circulatory pathway has the potential to identify novel biomarkers and therapeutic targets for systemic sclerosis while providing fundamental insights into EV-mediated inter-organ communication in humans.

Conditions

Systemic Sclerosis; Pulmonary Arterial Hypertension; Digital Ulcers; Vascular Complications

Outcome Measures

Primary Outcomes (2)

• Transcardiopulmonary extracellular vesicle gradient

  Arteriovenous differences between the pulmonary artery and the ascending aorta in extracellular vesicle characteristics, including particle concentration, size distribution, protein expression profile, and RNA expression profile. Treatment failure in patients with pulmonary arterial hypertension at 24 weeks, defined as the occurrence of at least one of the following events: an improvement of less than 30 meters in the 6-minute walk distance (6MWD); a reduction in NT-proBNP of less than 30% in patients with baseline levels \>300 pg/mL; worsening of World Health Organization (WHO) functional class; or death due to complications of pulmonary arterial hypertension. Treatment failure in patients with recurrent digital ulcers, defined as the development of new digital ulcers or gangrene at sites previously affected by digital ulcers.

  Periprocedural (during right heart catheterization).

• Peripheral extracellular vesicle gradient

  Arteriovenous differences between the cephalic vein and the radial artery in extracellular vesicle characteristics, including particle concentration, size distribution, protein expression profile, and RNA expression profile.

  Periprocedural.

Secondary Outcomes (2)

• Treatment failure in participants with pulmonary arterial hypertension.

  24 weeks.

• Treatment failure in participants with recurrent digital ulcers.

  24 weeks.

Study Arms (1)

Diagnosis of systemic sclerosis according to the 2013 ACR/EULAR classification criteria.

EXPERIMENTAL

* Male and female patients aged 45-75 years. * Diagnosis of systemic sclerosis according to the 2013 ACR/EULAR classification criteria. * High risk of pulmonary arterial hypertension based on the DETECT algorithm. * Stable treatment with vasoactive, vasodilator, and immunosuppressive therapies for at least 3 months prior to blood sampling.

Diagnostic Test: Blood sampling, nailfold capillaroscopy

Interventions

Blood sampling, nailfold capillaroscopy DIAGNOSTIC_TEST

Blood collection during right heart catheterization

Diagnosis of systemic sclerosis according to the 2013 ACR/EULAR classification criteria.

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged 45-75 years Diagnosis of systemic sclerosis according to the 2013 ACR/EULAR classification criteria High risk of pulmonary arterial hypertension based on the DETECT algorithm Stable treatment with vasoactive, vasodilator, and immunosuppressive therapies for at least 3 months prior to blood sampling

You may not qualify if:

• Previous diagnosis of pulmonary arterial hypertension confirmed by right heart catheterization Interstitial lung involvement affecting more than 10% of the lung parenchyma Left-sided heart failure (NYHA class 3-4) Evidence of chronic thromboembolic pulmonary disease on contrast-enhanced CT scan Major contraindications to right heart catheterization or coronary angiography Inability to provide informed consent

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

MeSH Terms

Conditions

Scleroderma, Systemic; Pulmonary Arterial Hypertension; digital ulcers

Interventions

Blood Specimen Collection; Microscopic Angioscopy

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Intravital Microscopy; Microscopy; Diagnostic Imaging; Diagnostic Techniques, Cardiovascular

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share