Clinical Research Directory

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

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.

Bosentan in Systemic Sclerosis

The effect of bosentan on digital ulcers (DU) was studied in two randomized placebo-controlled trials (RAPIDS-1 and RAPIDS-2). A limitation of these studies was the heterogeneous study population. More importantly, there were no endpoints that assessed changes in vasculopathy and / or perfusion. Laser Doppler imaging has been shown to effectively demonstrate blood flow restrictions in the hands of patients with Systemic Sclerosis (SSc). The relation between blood flow restriction in the hands measured by laser Doppler imaging and the extent of DU disease has not been studied. The current study will attempt to demonstrate this relation. In addition, the impact of bosentan on the blood flow in the hands, in a defined cohort of SSc-DU patients with a history of DU within the past 2 years and a clinically relevant reduction of blood flow in the hands, will be assessed.