Neutrophils as Prognostic Factors in Granulomatosis With Polyangiitis (Formerly Named Wegener's Granulomatosis) (NeutroVasc)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01862068
First received: January 1, 2013
Last updated: May 22, 2013
Last verified: May 2013
  Purpose

Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitis are rare diseases characterized by inflammation of blood vessels. Among the numerous cell types that play a role in vasculitis, one of the key actors is the neutrophil. Neutrophils are equipped with very powerful molecules that they use to destroy the invading microbes. Therefore, the mechanisms controlling neutrophil activation should be tightly controlled. If that is not the case, neutrophils may destroy the tissues of the host. This is what happens during chronic inflammation in vasculitis. Autoantibodies directed against neutrophils, ANCA, produced thus demonstrating that neutrophils are also targets of the immune system in these diseases. In addition, molecular studies provided evidence that genes normally silenced in mature neutrophils under normal conditions can be re-expressed in neutrophils from patients with ANCA-associated vasculitis thus strongly suggesting a profound deregulation of neutrophil functions in these conditions. Notably, the investigators have preliminary data showing that neutrophils from patients with granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis), an ANCA-associated vasculitis, interfere with the normal phase of resolution of inflammation.

The objective of the investigators' study is to understand the mechanisms underlying this increased activation state and determine if neutrophils could be used to define prognostic markers by clinicians to optimize patients' care. Therefore, the investigators plan to study the expression of proteins implicated in GPA pathophysiology at the membrane of neutrophils when they undergo apoptosis. The investigators will also study the deregulation of protein expression in neutrophils. This point will be the molecular translation of neutrophil deregulation. This technique is powerful and well adapted to identify by mass spectrometry the proteins that will be differentially expressed between the control and the disease state. After identification of proteins differentially expressed in patients with GPA, the investigators will further investigate whether their expression is modulated during the disease course and/or modified by the treatment.

The investigators believe that understanding these neutrophil perturbations can lead to better monitoring of disease activity. Ultimately, the investigators may propose more targeted anti-inflammatory therapies which would be better tolerated by patients. the investigators also can identify new markers for disease activity which allow clinicians to define a better therapeutic strategy.


Condition Intervention
Granulomatosis With Polyangiitis
Other: Blood samples and clinical data
Other: Blood sample

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Neutrophils Function and Identification of Prognostic Factors in Granulomatosis With Polyangiitis (Formerly Named Wegener's Granulomatosis).

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • level of neutrophils [ Time Frame: At Day 0 ] [ Designated as safety issue: No ]
    Proteomic analysis of neutrophils compared to healthy donors and MPA (microscopic polyangiitis) patients


Biospecimen Retention:   Samples Without DNA

Whole blood


Estimated Enrollment: 220
Study Start Date: May 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
GPA patients
GPA patients with an active disease at inclusion
Other: Blood samples and clinical data
Blood samples will be performed at inclusion and at 12 months from all patients (2 groups GPA and MPA)
MPA patients Other: Blood samples and clinical data
Blood samples will be performed at inclusion and at 12 months from all patients (2 groups GPA and MPA)
Healthy Blood Donors Other: Blood sample
Blood sample will be performed at inclusion from all healthy patients

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

GPA (Granulomatosis with polyangiitis) patients with an active disease at inclusion

Criteria

Inclusion Criteria:

For patients with GPA

  • Systemic or localized GPA with ACR (American College of Rheumatology) criteria.
  • BVAS > 3.
  • ANCA anti-PR3 or anti-MPO
  • Consent form signed

For patients with MPA

  • Systemic MPA with Chapel Hill criteria.
  • BVAS > 3.
  • ANCA anti-MPO
  • Consent form signed

Exclusion Criteria:

  • Pregnancy
  • <18 yr
  • Malignancy
  • Infectious diseases: HIV, HBV, HCV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01862068

Contacts
Contact: Luc Mouthon, MD, PhD + 33 1 58 41 20 31 luc.mouthon@cch.aphp.fr
Contact: Laurence Lecomte, PhD +33 1 71 19 64 94 laurence.lecomte@nck.aphp.fr

Locations
France
Cochin Hospital Recruiting
Paris, France, 75014
Contact: Luc Mouthon, MD, PhD    +33 1 58 41 20 31    luc.mouthon@cch.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01862068     History of Changes
Other Study ID Numbers: NI 10017
Study First Received: January 1, 2013
Last Updated: May 22, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Pronostic factors
Neutrophils
Granulomatosis with polyangiitis
Microscopic polyangiitis
ANCA associated vasculitis
Proteomics

Additional relevant MeSH terms:
Wegener Granulomatosis
Systemic Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Autoimmune Diseases
Cardiovascular Diseases
Immune System Diseases
Lung Diseases
Lung Diseases, Interstitial
Respiratory Tract Diseases
Vascular Diseases
Vasculitis

ClinicalTrials.gov processed this record on October 20, 2014