Soluble CD95 Ligand Role in the Pathophysiology of Antineutrophil Cytoplasmic Antibody (ANCA) Associated Vasculitis (VASC-FAS)

Soluble CD95 Ligand Role in the Pathophysiology of ANCA Associated Vasculitis

The study aims at defining the role of soluble CD95 Ligand in the physiopathology of a rare group of inflammatory diseases: ANCA associated vasculitis. Soluble CD95 Ligand might have a prognostic and diagnostic interest as well as potential for the discovery of new therapeutic strategies.

Study Overview

• Status: Recruiting
• Conditions: ANCA Associated Vasculitis
• Intervention / Treatment: Biological: blood sample; Biological: urine sample

Detailed Description

ANCA associated vasculitis are a rare group of diseases and potentially life-threatening inflammatory conditions. There is an urgent need to describe prognostic factors and to discover new therapeutic pathways. Soluble CD95-L is a cleaved part of CD95-L which binds the CD95 Death receptor. s-CD95-L has pro-inflammatory properties for Th17 lymphocytes and Neutrophils, two cells implicated in ANCA associated vasculitis. It also plays a role in systemic lupus erythematosus (which present with the same type of renal glomerulonephritis as ANCA-associated vasculitis). Finally, it has already be found elevated in this group of diseases. The investigators hypothesized that s-CD95-L levels might be a prognostic factor in ANCA associated vasculitis and the study of the molecular mechanisms involved could provide new therapeutic targets.

The study will recruit 50 patients with ANCA associated vasculitis followed in Bordeaux University Hospital. Among classical disease activity information, blood and urine samples will be collected at each visit to study s-CD95-L. Fundamental research will be realized on patients' sample to study molecular mechanisms involved.

Clinical and biological disease activity, treatment and outcomes will be studied in correlation with s-CD95-L to describe their potential prognostic role. Patients will be followed at regular intervals, as their usual follow-up would request. No extra visit will be needed and blood samples will be drawn at the same time as those drawn for clinical purposes.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Patrick BLANCO, Prof; Phone Number: +33 (0)5 56 79 56 45; Email: patrick.blanco@chu-bordeaux.fr
• Study Contact Backup: Name: Thomas BARNETCHE, PhD; Phone Number: +33 (0)5.57.82.04.93; Email: thomas.barnetche@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France
    • Recruiting
    • CHU de Bordeaux - Service d'Immunologie et Immunogénétique
    • Contact: Patrick BLANCO, Prof; Phone Number: +33 (0)5 56 79 56 45; Email: patrick.blanco@chu-bordeaux.fr
    • Contact: Thomas BARNETCHE, PhD; Phone Number: +33 (0)5.57.82.04.93; Email: thomas.barnetche@chu-bordeaux.fr
    • Principal Investigator: Patrick BLANCO, Prof
    • Sub-Investigator: Marie-Elise TRUCHETET, MD, PhD
    • Sub-Investigator: Pierre DUFFAU, MD, PhD
    • Sub-Investigator: Estibaliz LAZARO, Prof
    • Sub-Investigator: Christophe RICHEZ, Prof
    • Sub-Investigator: Lionel COUZI, Prof
    • Sub-Investigator: Julien SENESCHAL, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of ANCA associated vasculitis according to the Chapel-Hill Consensus Conference - 2012 modified version
• Age ≥ 18 years
• being affiliated to health insurance
• willing to participate and to sign informed consent.

Exclusion Criteria:

• Pregnant or breastfeeding women,
• patient concerned by articles L 1121-5 to L 1121-8 (persons deprived of their liberty by a judicial or administrative decision, minors, persons of legal age who are the object of a legal protection measure or unable to express their consent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANCA associated vasculitis	Biological: blood sample; 30 ml whole blood for Peripheral blood mononuclear cell (PBMC) and monocytes isolation; Biological: urine sample; 6 ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of quantitative levels of s-CD95-L in ANCA associated vasculitis between baseline and Month 12	At baseline (Day 0) and 12 months from baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of disease activity scores for ANCA associated vasculitis between baseline and Month 12	Birmingham Vasculitis Activity Score - Version 3 (BVAS 3.0) The Birmingham Vasculitis Activity Score (BVAS) is a method for assessing the activity of vasculitis. Note that scoring ranges are higher when any of the features are new or worse. Creatinine levels can be scored at patient's first assessment only. The maximum score is 63 points for present symptoms and 32 points for new symptoms or symptoms which had worsened within the previous weeks.	At baseline (Day 0) and 12 months from baseline
Change of disease activity scores for ANCA associated vasculitis between baseline and Month 12	Vasculitis Damage Index (VDI)	At baseline (Day 0) and 12 months from baseline
Change of quantification of s-CD95-L in the blood and urine samples of ANCA associated vasculitis between baseline and Month 12		At baseline (Day 0) and 12 months from baseline
Change of quantification of ANCA in the blood samples of ANCA associated vasculitis between baseline and Month 12		At baseline (Day 0) and 12 months from baseline

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Collaborators: National Research Agency, France
• Investigators: Principal Investigator: Patrick BLANCO, Prof, CHU Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: October 4, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ANCA associated vasculitis; Granulomatosis with polyangiitis; microscopic polyangiitis; eosinophilic granulomatosis with polyangiitis; soluble-CD95-Ligand
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vascular; Systemic Vasculitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Other Study ID Numbers: CHUBX 2018/22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No