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Neutrophil Extracellular Traps in Systemic Sclerosis (NET-SSC)

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ClinicalTrials.gov Identifier: NCT03374618
Recruitment Status : Recruiting
First Posted : December 15, 2017
Last Update Posted : December 15, 2017
Sponsor:
Information provided by (Responsible Party):
CHU de Reims

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.

We hypothesis that this phenomenon could be dysregulated in SSC as in SLE and could play a prominent role in the induction of autoimmunity, as well as in the induction and perpetuation of organ damages.


Condition or disease Intervention/treatment Phase
Systemic Lupus Erythematosus Systemic Sclerosis Other: Blood sample Not Applicable

Detailed Description:

This study is designed to assess the role of neutrophil extracellular traps (NETs) in systemic sclerosis as well as to evaluate the correlation between NETs production and NETs composition and the different complications and phenotypes observed in SSC.

30 SSC patients, 30 SLE patients and 60 healthy subjects will be recruited. Blood samples will be collected to obtain plasma, serum and polynuclear neutrophils by negative selection.

  1. The main aim of the study is to evaluate the quantity of NETs induced by serum from SSc patients on neutrophils from either healthy or SSC patients in vitro. The quantity of NETs produced by different populations of neutrophils in contact with sera from SSC will be compared with those produced by the same different populations of neutrophils in contact with sera from SLE, and healthy subjects (two control populations).
  2. Other objectives:

    • To assess the composition of the NETs produced by different populations of neutrophils exposed to serum from SSC, SLE and healthy subjects.
    • To correlate the quantity and the composition of NETS with clinical phenotype in SSc
    • To assess the role of serum cytokines in Nets production in SSC.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Neutrophil Extracellular Traps in Different Forms of Systemic Sclerosis
Actual Study Start Date : October 6, 2017
Estimated Primary Completion Date : October 6, 2019
Estimated Study Completion Date : October 7, 2019


Arm Intervention/treatment
Experimental: systemic lupus erythematosus
adult with systemic lupus erythematosus
Other: Blood sample
Blood sample to quantify and qualify netosis in vivo and ex vivo after different stimulations in SSC, SLA and healthy controls

Experimental: systemic sclerosis
adult with systemic sclerosis
Other: Blood sample
Blood sample to quantify and qualify netosis in vivo and ex vivo after different stimulations in SSC, SLA and healthy controls

healthy volunteers
healthy volunteer (adult)
Other: Blood sample
Blood sample to quantify and qualify netosis in vivo and ex vivo after different stimulations in SSC, SLA and healthy controls




Primary Outcome Measures :
  1. Quantification of neutrophil extracellular traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, SLE and healthy controls. [ Time Frame: Day 0 ]
    Comparative analysis of the quantity of neutrophil extracellular traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, SLE and healthy controls. Neutrophils from SSC, SLE and healthy subjects will be used.


Secondary Outcome Measures :
  1. Analysis of the composition of neutrophil extracellular traps [ Time Frame: Day 0 ]
    Comparative analysis of the composition of neutrophil extracellular traps (NETs) generated after stimulation of neutrophils in vitro by serum from SSC, SLE and healthy controls. Neutrophils from SSC, SLE and healthy subjects will be used.

  2. Analysis of the cytokines influencing NETs production in vitro [ Time Frame: Day 0 ]
    Comparative analysis of the quantity of neutrophil extracellular traps (NETs) generated after stimulation of neutrophils from SSC patients in vitro by differents cytokines



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

for patients of arm 1:

  • patients with systemic lupus erythematosus
  • patients consenting to participate to the study
  • patients enrolled in the national healthcare insurance program

for patients of arm 2:

  • patients with systemic sclerosis
  • patients consenting to participate to the study
  • patients enrolled in the national healthcare insurance program

For patients of arm 3 (healthy volunteers)

  • Patients without Chronic inflammatory systemic disease
  • Patients without Current or past neoplasy,
  • patients without chronic metabolic pathology
  • patients without treatment by anti inflammatory or corticotherapy for the last 15 days,
  • patients without infectious pathology or inflammatory acute for the last 15 days

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374618


Contacts
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Contact: Amélie SERVETTAZ 032683269 ext +33 aservettaz@chu-reims.fr
Contact: Coralie BARBE cbarbe@chu-reims.fr

Locations
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France
Damien JOLLY Recruiting
Reims, France
Contact: Amélie SERVETTAZ       aservettaz@chu-reims.fr   
Sponsors and Collaborators
CHU de Reims

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Responsible Party: CHU de Reims
ClinicalTrials.gov Identifier: NCT03374618     History of Changes
Other Study ID Numbers: PO17014
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: December 15, 2017
Last Verified: October 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Pathologic Processes
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Skin Diseases