An observational study in Systemic Sclerosis (SSc), Diffuse Cutaneous Systemic Sclerosis and Skin Fibrosis, sponsored by Fondazione Policlinico Universitario Campus Bio-Medico. Not yet recruiting at 1 site in Italy. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-11.
Sponsored by Fondazione Policlinico Universitario Campus Bio-Medico · Observational
Systemic Sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by microvascular injury, immune activation, and progressive fibrosis of the skin and internal organs. Diffuse cutaneous SSc (dcSSc), particularly in its early phase, is associated with aggressive fibrotic evolution and high morbidity. Despite advances in immunomodulatory therapy, no treatment has proven capable of consistently halting or reversing fibrosis, highlighting the need for new mechanistic targets.
TL1A (TNF-like ligand 1A) is a cytokine of the TNF superfamily expressed by endothelial and immune cells, which interacts with death receptor 3 (DR3) to regulate immune activation, endothelial dysfunction, and tissue remodeling. Elevated TL1A levels have been observed in SSc patients and correlate with disease activity. TL1A has also been shown to promote lung fibrosis in preclinical models.
The FIBROSTOP study is a proof-of-concept, in vitro, interventional study on biological samples aimed at elucidating the immunological and fibrotic mechanisms regulated by TL1A, and at assessing whether TL1A inhibition can reverse pathogenic processes in SSc.
Ten (n=10) patients with early diffuse cutaneous SSc and ten (n=10) age- and sex-matched healthy controls will be enrolled at a single center (Fondazione Policlinico Universitario Campus Bio-Medico, Rome). Each participant will undergo a single visit (T0) involving peripheral blood sampling and skin biopsy. No follow-up visits are planned.
The study pursues three co-primary objectives: (1) evaluating the role of TL1A and its inhibition in modulating T lymphocyte activity; (2) assessing the effects of TL1A and its inhibition on endothelial cell activation and function; (3) investigating the impact of TL1A and its inhibition on fibrotic remodeling in ex vivo SSc skin cultures using single-cell RNA sequencing.
The findings may inform future targeted antifibrotic interventions in SSc and other fibrotic diseases.
BACKGROUND AND RATIONALE
Systemic sclerosis (SSc) is an immune-mediated connective tissue disease characterized by fibrosis and vasculopathy. SSc is a heterogeneous orphan disease with a broad spectrum of organ involvement and life-threatening manifestations. The hallmark feature is the presence of thickened and hardened skin (scleroderma). The disease is divided into limited cutaneous and diffuse cutaneous SSc subsets based on the extent of skin involvement. Diffuse cutaneous SSc (dcSSc) is associated with a higher risk of interstitial lung disease, renal crisis, and cardiac involvement.
The pathophysiology of SSc involves a progressive self-amplifying process starting with microvascular/endothelial damage, followed by autoimmune response, inflammation, and fibrosis. T lymphocytes, particularly CD4+ T cells with a predominant Th2 cytokine profile, play an essential role in SSc pathogenesis. Regulatory T cells (Tregs) show decreased functional ability to suppress effector T cells.
TL1A (TNF-like cytokine 1A) is a member of the TNF superfamily constitutively expressed in endothelial cells and upregulated in response to TNF-α stimulation. TL1A binds to its receptor death receptor 3 (DR3), activating downstream signaling involved in innate and adaptive immune homeostasis. Elevated TL1A levels have been detected in serum of SSc patients compared to healthy subjects and correlate with disease activity. TL1A has been demonstrated to promote lung fibrosis in bleomycin-induced mouse models. The ATHENA-SSc-ILD study is currently evaluating Tulisokibart, a TL1A inhibitor, for SSc-associated interstitial lung disease.
STUDY DESIGN
FIBROSTOP is a monocentric, non-profit, interventional proof-of-concept in vitro study on biological samples. The study is funded by an unconditional grant from MSD Italia S.r.l. and conducted at the Fondazione Policlinico Universitario Campus Bio-Medico, Rome (Principal Investigator: Prof. Roberto Giacomelli).
OBJECTIVES AND ENDPOINTS
Co-Primary Objectives:
Co-Primary Endpoints:
STUDY POPULATION AND PROCEDURES
Ten (n=10) patients with SSc (ACR/EULAR 2013 criteria, diffuse cutaneous subset per LeRoy et al. 1988, disease onset ≤5 years from first non-Raynaud symptom) and ten (n=10) age- and sex-matched healthy controls will be enrolled consecutively over approximately 12 months.
Each participant undergoes a single study visit (T0) involving:
STATISTICAL CONSIDERATIONS
The FIBROSTOP study is exploratory in nature; no formal sample size calculation is required. Statistical analyses will include Student's t-test or Mann-Whitney U test for two-group comparisons, one-way/two-way ANOVA or Kruskal-Wallis test for multiple-group comparisons, and Spearman's rank correlation for continuous variables. Transcriptomic data will be analyzed using DESeq2 (bulk RNA-seq) and Seurat (scRNA-seq) pipelines. Pathway enrichment analyses will use Reactome, Gene Ontology (GO), and KEGG databases.
DURATION
Total study duration: 24 months (12 months enrollment + 12 months data generation and analysis). Each participant takes part in a single visit only.
310 studies on the registry are indexed under Scleroderma, Diffuse; 76 are open to participants now.
This study's planned enrollment of 20 is below the median of 113 across 68 observational studies indexed under Scleroderma, Diffuse.
Browse Scleroderma, Diffuse studies →Fondazione Policlinico Universitario Campus Bio-Medico is the lead sponsor of 29 studies on the registry; 20 are open to participants now.
Compared within Scleroderma, Diffuse, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Scleroderma, Systemic. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Ten patients with early diffuse cutaneous Systemic Sclerosis (dcSSc) fulfilling the 2013 ACR/EULAR classification criteria and the LeRoy subset definition, with disease onset ≤5 years from the first non-Raynaud symptom, consecutively recruited from the Scleroderma Unit of Fondazione Policlinico Universitario Campus Bio-Medico, Rome. Ten age- and sex-matched healthy controls without SSc diagnosis, donating peripheral blood and residual skin tissue from elective surgical procedures or voluntary donation.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For both SSc and healthy control populations:
For SSc population only:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ten patients with early diffuse cutaneous Systemic Sclerosis (dcSSc) fulfilling the 2013 ACR/EULAR classification criteria and the LeRoy subset definition, with disease onset ≤5 years from the first non-Raynaud symptom, on stable immunosuppressive therapy. Each participant undergoes a single visit (T0) for peripheral blood sampling and skin punch biopsy (3x3 mm).
Other: TL1A stimulation and inhibition (in vitro)
Ten age- and sex-matched donors not affected by SSc. Peripheral blood samples are collected for research purposes. Skin samples are derived from residual tissue of minor elective surgical procedures or voluntary skin donation.
Other: TL1A stimulation and inhibition (in vitro)
Biological samples (T-cell subsets, HUVECs, and ex vivo skin cultures) are treated in vitro under experimental conditions including TL1A stimulation, DR3 silencing by siRNA, and TL1A neutralizing antibody. No intervention is administered to study participants.
T-cell cytokine production and activation following TL1A stimulation and inhibition
Changes in cytokine production (IFN-gamma, IL-1beta, IL-6, IL-10, IL-17A, IL-35, TNF-alpha, TGF-beta), cellular activation, autophagy, apoptosis, and necroptosis in CD4+, CD8+, and Treg subsets isolated from SSc patients and healthy controls, following TL1A stimulation and DR3 silencing by siRNA, assessed by multiplex assays, flow cytometry, and Western blot.
Time frame: Within 12 months from biological sample collection (single visit at T0)
Endothelial cell activation and angiogenic capacity following TL1A stimulation and inhibition
Changes in expression of P-selectin, E-selectin, ICAM-1, VCAM-1, and Matrigel tube formation capacity in HUVECs cultured with SSc serum and treated with TL1A stimulation and DR3 silencing by siRNA, assessed by Western blot, Matrigel assay, and bulk RNA sequencing.
Time frame: Within 12 months from biological sample collection (single visit at T0)
Fibrotic and inflammatory marker expression in ex vivo skin cultures following TL1A modulation
Expression of fibrotic markers (Col-1, alphaSMA) and transcriptional reprogramming in fibroblasts, lymphocytes, and endothelial cells in ex vivo skin cultures treated with TL1A and TL1A neutralizing antibody, assessed by single-cell RNA sequencing (scRNA-seq).
Time frame: Within 12 months from biological sample collection (single visit at T0)
Plan to share: No
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