Study of One Protein Implicated in Wegener Disease

Wegener's Granulomatosis Clinical Trial

— DAP12WEGENER  

Official title:

Activating Receptors and DAP12 Protein in Wegener's Granulomatosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01167491
• Other study ID #: P081238
• Status: Completed
• Phase: N/A
• First received: July 12, 2010
• Last updated: April 20, 2015
• Start date: May 2010
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: September 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Wegener Granulomatosis
• Wegener's Granulomatosis

Intervention

Biological:
• Physiopathology Endpoint Classification
Blood samples will be collected during a routine medical visit.

Locations

Country	Name	City	State
France	Medecine Interne Hôpital Saint Louis	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	level of mRNA expression of DAP12	Measure:level of mRNA expression of DAP12 by RT-PCR in CD4+T cells, macrophages and neutrophils	less than 24 hours	No
Secondary	level of expression of DAP 12 downstream signalling proteins	Measure: level of expression of DAP 12 downstream signalling proteins in CD4+ T cells, macrophages and neutrophils	Less than 24 hours	No