NCT06462768

Brief Summary

Systemic SClerosis (SSC) is a systemic disease characterized by limited or diffuse cutaneous sclerosis, microangiopathy, overproduction of autoantibodies and variable organ damage due to vasculopathy and/or fibrosis. The loss of self-tolerance is believed to be caused by the dysregulation of both innate and adaptive immune systems and may involve Reactive Oxygen Species (ROS). Neutrophils are potent producers of ROS and may play a role in endothelial cells and fibrobasts dysfunction, as in autoantibodies generation. However, their role in SSC pathogenesis remains to be determined. Recent studies discovered abnormal regulation of Neutrophil Extracellular Traps (NETs) in other auto-immune diseases such as Systemic Lupus Erythematosus (SLE). NETs are web-like structures composed of chromatin backbones and granular molecules. They are released by activated neutrophils through a process called "NETosis". Nets were first described in 2004 as a novel host defense mechanism to trap and kill foreign pathogens. Recent evidence shows that NETs also participate in the pathogenesis of a variety of inflammatory and autoimmune diseases, including SLE. The investigators recently highlighted this phenomenon in SSc, especially in patients with vascular complications and/or at a early stage of the disease. The investigators will now explore the factors implicated in this dysregulation of NETosis in SSc.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
260

participants targeted

Target at P75+ for all trials

Timeline
36mo left

Started Nov 2023

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress45%
Nov 2023Apr 2029

Study Start

First participant enrolled

November 27, 2023

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

June 12, 2024

Completed
5 days until next milestone

First Posted

Study publicly available on registry

June 17, 2024

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 27, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 27, 2029

Last Updated

June 17, 2024

Status Verified

June 1, 2024

Enrollment Period

4.9 years

First QC Date

June 12, 2024

Last Update Submit

June 12, 2024

Conditions

Keywords

Systemic sclerosisNETosispolymorphonuclear neutrophil

Outcome Measures

Primary Outcomes (1)

  • Quantification of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, SLE and healthy controls.

    Comparative analysis of the quantity of Neutrophil Extracellular Traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, other connective tissue diseases and healthy controls. Neutrophils from SSC, other connective tissue diseases and healthy subjects will be used.

    Day 0

Secondary Outcomes (2)

  • Analysis of the composition of Neutrophil Extracellular Traps (NETs)

    Day 0

  • Analysis of the cytokines influencing Neutrophil Extracellular Traps NETs production in vitro

    Day 0

Study Arms (3)

Adult with SSc

Adult with SSc

Other: Blood sample

Other connective tissue disease

Adult with other connective tissue disease

Other: Blood sample

Control

Healthy adult volunteer

Other: Blood sample

Interventions

Blood sample to quantify and qualify NETosis in vivo and ex vivo after different stimulations.

Adult with SScControlOther connective tissue disease

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Group 1 : Adult with SSc Group 2 : Adult with other connective tissue disease Group 3 : Healthy adult volunteer

You may qualify if:

  • \*For patients of group 1:
  • Patients with systemic sclerosis (ACR-EULAR Criteria)
  • Patients taking care of in internal medicine or in dermatology department's of the university hospital of Reims
  • Patients consenting to participate to the study
  • Patients enrolled in the national healthcare insurance program
  • For patients of group 2:
  • Patients with other connective tissue disease (ACR specific-disease criteria)
  • Patients taking care of in internal medicine or in dermatology department's of the university hospital of Reims
  • Patients consenting to participate to the study
  • Patients enrolled in the national healthcare insurance program
  • For patients of group 3 (healthy volunteers)
  • Patients eligible for blood donation (blood donation regulation criteria of January 11th 2022 decree)
  • Patients without medical history of autoimmune systemic or chronic inflammatory systemic disease,
  • Patients without current or past neoplasy disease,
  • Patients without chronic metabolic pathology
  • +3 more criteria

You may not qualify if:

  • Patients/Healthy volunteers under 18 years old
  • Patients/Healthy volunteers protected by the law
  • Patients/Healthy volunteers not consenting to participate to the study after information
  • Pregnant or breastfeeding women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Chu Reims

Reims, 51092, France

RECRUITING

Related Publications (1)

  • Didier K, Giusti D, Le Jan S, Terryn C, Muller C, Pham BN, Le Naour R, Antonicelli FD, Servettaz A. Neutrophil Extracellular Traps Generation Relates with Early Stage and Vascular Complications in Systemic Sclerosis. J Clin Med. 2020 Jul 7;9(7):2136. doi: 10.3390/jcm9072136.

    PMID: 32645862BACKGROUND

MeSH Terms

Conditions

Scleroderma, SystemicLupus Erythematosus, SystemicDermatomyositisAnti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Connective Tissue DiseasesSkin and Connective Tissue DiseasesSkin DiseasesAutoimmune DiseasesImmune System DiseasesPolymyositisMyositisMuscular DiseasesMusculoskeletal DiseasesNeuromuscular DiseasesNervous System DiseasesSystemic VasculitisVasculitisVascular DiseasesCardiovascular DiseasesSkin Diseases, Vascular

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative Techniques

Central Study Contacts

Kevin DIDIER, Dr.

CONTACT

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 12, 2024

First Posted

June 17, 2024

Study Start

November 27, 2023

Primary Completion (Estimated)

October 27, 2028

Study Completion (Estimated)

April 27, 2029

Last Updated

June 17, 2024

Record last verified: 2024-06

Locations