Longitudinal Protocol for Granulomatosis With Polyangiitis (Wegener's) and Microscopic Polyangiitis

Microscopic Polyangiitis Clinical Trial

Official title:

Determining Disease Activity Biomarkers in Individuals With Granulomatosis With Polyangiitis (Wegener's) and Microscopic Polyangiitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00315393
• Other study ID #: VCRC5505
• Secondary ID: U54AR057319
• Status: Completed
• Start date: April 2006
• Est. completion date: December 2019

Study information

• Verified date: July 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are two rare immune system disorders that cause the inflammation of blood vessels, or vasculitis. In order to properly treat these diseases, it is critical that the level of disease activity can be determined over the course of the disease. The purpose of this study is to determine new biological markers, or biomarkers, that may be used to assess the severity of disease in people with GPA or MPA.

Description:

GPA and MPA are two autoimmune disorders that cause systemic vasculitis. GPA commonly affects the upper respiratory tract, the lungs, and the kidneys. MPA is marked by kidney inflammation, weight loss, skin lesions, nerve damage, and fever. Many patients with WG or MPA show no visible symptoms of active disease; it is known that underlying subclinical disease activity leads to long-term damage in these patients. Also, because it is difficult to monitor WG and MPA disease activity, it is difficult for clinicians to know when and how to treat these patients. This study will use new scientific methods to identify new biomarkers that can be used to monitor disease activity in GPA and MPA patients. These biomarkers may be used to help direct clinical care for GPA and MPA patients and assist in future drug development.

Study visits will occur monthly for the first year, then every 3 months thereafter for the remainder of the study. Blood and urine collection will occur at every visit. A physical exam and medical and medication history will occur every 3 months; also, participants will be asked to complete several questionnaires to assess disease activity, health status, and tobacco, alcohol, and drug use. Participants may have additional study visits if a disease flare or disease-related complications occur during the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1046
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Diagnosis of GPA or MPA. Widely accepted diagnostic criteria, as opposed to classification criteria or definitions, have not been developed for GPA and MPA.

• For diagnosis of GPA, meets at least 2 of the following 5 modified American College of Rheumatology (ACR) criteria:

1. Nasal or oral inflammation with oral ulcers or nasal discharge with pus or blood

2. Abnormal chest radiograph with nodules, fixed infiltrates, or cavities

3. Urinary sediment with microhematuria or red cell casts

4. Granulomatous inflammation within the wall of an artery or in the perivascular area on biopsy

5. Antineutrophil cytoplasmic antibody (ANCA) positive by enzyme immunoassay for either PR3- or MPO-ANCA

• For diagnosis of MPA, meets the Chapel Hill Consensus Conference Definition for MPA:

1. Necrotizing vasculitis, with few or no immune deposits, that affects small vessels (i.e., capillaries, venules, arterioles)

2. Necrotizing arteritis involving small- and medium-sized arteries may be present

3. Necrotizing glomerulonephritis is very common

4. Pulmonary capillaritis often occurs

• Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

• Simultaneous diagnoses of both GPA and MPA

• Granulomatosis with polyangiitis (Churg-Strauss)

• Takayasu's arteritis

• Giant cell arteritis

• Polyarteritis nodosa

• Cogan's syndrome

• Behcet's disease

• Sarcoidosis

• Kawasaki disease

• Tuberculosis or any atypical mycobacterial infections

• Deep fungal infections

• Lymphoma, lymphomatoid granulomatosis, or any other type of cancer that mimics anti-neutrophil cytoplasmic antibody-associated vasculitis (AAVs)

• Cryoglobulinemic vasculitis

• Systemic lupus erythematosus

• Rheumatoid arthritis

• Mixed connective tissue disease or any overlapping autoimmune syndrome

Related Conditions & MeSH terms

• Granulomatosis With Polyangiitis
• Microscopic Polyangiitis
• Systemic Vasculitis
• Wegener's

Locations

Country	Name	City	State
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
United States	Boston University School of Medicine	Boston	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Utah	Salt Lake City	Utah

Sponsors (4)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Office of Rare Diseases (ORD), Rare Diseases Clinical Research Network

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Borgmann S, Haubitz M. Genetic impact of pathogenesis and prognosis of ANCA-associated vasculitides. Clin Exp Rheumatol. 2004;22(6 Suppl 36):S79-86. Review. — View Citation

Cooley P, Taylor KH, Czika W, Seifer C, Taylor JF. Analysis of a biomarker for Wegener's granulomatosis. Int J Immunogenet. 2005 Aug;32(4):237-43. — View Citation

Jagiello P, Gross WL, Epplen JT. Complex genetics of Wegener granulomatosis. Autoimmun Rev. 2005 Jan;4(1):42-7. Review. — View Citation

Radice A, Sinico RA. Antineutrophil cytoplasmic antibodies (ANCA). Autoimmunity. 2005 Feb;38(1):93-103. Review. — View Citation

Stone JH, Rajapakse VN, Hoffman GS, Specks U, Merkel PA, Spiera RF, Davis JC, St Clair EW, McCune J, Ross S, Hitt BA, Veenstra TD, Conrads TP, Liotta LA, Petricoin EF 3rd; Wegener's Granulomatosis Etanercept Trial Research Group. A serum proteomic approach to gauging the state of remission in Wegener's granulomatosis. Arthritis Rheum. 2005 Mar;52(3):902-10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Discover biomarkers in GPA/MPA capable of measuring disease activity and response to treatment.		Study completion
Secondary	Measure the predictive value of biomarkers for clinical outcome in GPA/MPA		Study completion.

External Links

•   Rare Diseases Clinical Research Consortium
•   Vasculitis Clinical Research Consortium