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

Sponsor

University of Pennsylvania (Other)

Overall Status

Completed

CT.gov ID

NCT00315393

Collaborator

Office of Rare Diseases (ORD) (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH), Rare Diseases Clinical Research Network (Other)

1,046

Enrollment

Locations

164

Duration (Months)

130.8

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Granulomatosis With Polyangiitis Microscopic Polyangiitis Wegener's

Detailed 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.

Study Design

Study Type:

Observational

Actual Enrollment :

1046 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Apr 1, 2006

Actual Primary Completion Date :

Dec 1, 2019

Actual Study Completion Date :

Dec 1, 2019

Outcome Measures

Primary Outcome Measures

Discover biomarkers in GPA/MPA capable of measuring disease activity and response to treatment. [Study completion]

Secondary Outcome Measures

Measure the predictive value of biomarkers for clinical outcome in GPA/MPA [Study completion.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Nasal or oral inflammation with oral ulcers or nasal discharge with pus or blood
Abnormal chest radiograph with nodules, fixed infiltrates, or cavities
Urinary sediment with microhematuria or red cell casts
Granulomatous inflammation within the wall of an artery or in the perivascular area on biopsy
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:

Necrotizing vasculitis, with few or no immune deposits, that affects small vessels (i.e., capillaries, venules, arterioles)
Necrotizing arteritis involving small- and medium-sized arteries may be present
Necrotizing glomerulonephritis is very common
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston University School of Medicine	Boston	Massachusetts	United States	02118
2	Mayo Clinic	Rochester	Minnesota	United States	55905
3	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
4	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
5	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15260
6	University of Utah	Salt Lake City	Utah	United States	84112
7	St. Joseph's Healthcare	Hamilton	Ontario	Canada
8	Mount Sinai Hospital	Toronto	Ontario	Canada	M5T 3L9