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Study of One Protein Implicated in Wegener Disease (DAP12WEGENER)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01167491
First received: July 12, 2010
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

The investigators recently showed an abnormal expansion of NK-like CD4+ T cells in Wegener's granulomatosis (WG), mainly in the diffuse vasculitis presentation. These cells expressed an assortment of activating NK cell receptors and their signaling partners, in particular DAP12. The investigators hypothesize that DAP12, or a downstream signaling target of DAP12, is the missing link between the different cell components involved in WG (neutrophils, macrophages, CD4 T cells).


Condition Intervention
Wegener's Granulomatosis
Biological: Physiopathology Endpoint Classification

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Activating Receptors and DAP12 Protein in Wegener's Granulomatosis

Resource links provided by NLM:


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

Primary Outcome Measures:
  • level of mRNA expression of DAP12 [ Time Frame: less than 24 hours ] [ Designated as safety issue: No ]
    Measure:level of mRNA expression of DAP12 by RT-PCR in CD4+T cells, macrophages and neutrophils


Secondary Outcome Measures:
  • level of expression of DAP 12 downstream signalling proteins [ Time Frame: Less than 24 hours ] [ Designated as safety issue: No ]
    Measure: level of expression of DAP 12 downstream signalling proteins in CD4+ T cells, macrophages and neutrophils


Estimated Enrollment: 150
Study Start Date: May 2010
Estimated Study Completion Date: June 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Disease group
Physiopathology
Biological: Physiopathology Endpoint Classification
Blood samples will be collected during a routine medical visit.
Other Name: Physiopathology Endpoint Classification

Detailed Description:

The investigators will test our hypothesis of "DAP-12 gain-of-function" by quantitative (mRNA and protein) and qualitative (DNA, signaling and cellular activation) analysis of the DAP12 signaling pathway in WG patients with localized (group 1; n=30) or diffuse WG (group 2; n=30) by comparison with patients with micro polyangitis (group 3; n=30), or with sarcoidosis ( group 4; n=30), and healthy blood donors (group 5; n=30). Blood samples will be collected during a routine medical visit. These results may help to design future therapeutic strategies based on modulation of specific intra-cellular pathways involved in the disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Group 1: WG, with granulomatous lesions limited to upper airway or lungs and no evidence of generalized vasculitis ,± biopsy, ± anti-PR3 ANCA
  • Group 2: WG with granulomatous lesions plus vasculitis expression (renal, neurological, skin, gut or heart involvement), ± biopsy, ± anti-PR3 ANCA
  • Group 3: Necrotizing vasculitis with no granulomatous lesions, ± PAUCI immune glomerulonephritis, ± anti-MPO ANCA
  • Group 4: clinical presentation compatible with sarcoidosis, ± biopsy, ± ECA elevated ± tuberculin anergy

Exclusion Criteria:

  • <18 years
  • Pregnancy or breastfeeding
  • Absence of signed informed consent
  • No affiliation to insurance
  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: NCT01167491

Locations
France
Medecine Interne Hôpital Saint Louis
Paris, France, 75010
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Mathilde De Menthon,, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01167491     History of Changes
Other Study ID Numbers: P081238
Study First Received: July 12, 2010
Last Updated: January 2, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Wegener
CD4+ T cells
DAP12
NKG2D

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

ClinicalTrials.gov processed this record on November 20, 2014