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

NCT ID: NCT00315393

Last Updated: 2022-07-12

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1046 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2019-12-31

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.

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.

Conditions

Granulomatosis With Polyangiitis; Microscopic Polyangiitis; Wegener's

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Office of Rare Diseases (ORD)

NIH

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Rare Diseases Clinical Research Network

NETWORK

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Peter Merkel

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter A. Merkel, MD, MPH

Role: STUDY_CHAIR

University of Pennsylvania

Locations

Boston University School of Medicine

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

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

Reference Type: BACKGROUND

PMID: 15675141 (View on PubMed)

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. doi: 10.1111/j.1744-313X.2005.00519.x.

Reference Type: BACKGROUND

PMID: 16026591 (View on PubMed)

Jagiello P, Gross WL, Epplen JT. Complex genetics of Wegener granulomatosis. Autoimmun Rev. 2005 Jan;4(1):42-7. doi: 10.1016/j.autrev.2004.06.003.

Reference Type: BACKGROUND

PMID: 15652778 (View on PubMed)

Radice A, Sinico RA. Antineutrophil cytoplasmic antibodies (ANCA). Autoimmunity. 2005 Feb;38(1):93-103. doi: 10.1080/08916930400022673.

Reference Type: BACKGROUND

PMID: 15804710 (View on PubMed)

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. doi: 10.1002/art.20938.

Reference Type: BACKGROUND

PMID: 15751091 (View on PubMed)

Tomasson G, Boers M, Walsh M, LaValley M, Cuthbertson D, Carette S, Davis JC, Hoffman GS, Khalidi NA, Langford CA, McAlear CA, McCune WJ, Monach PA, Seo P, Specks U, Spiera R, St Clair EW, Stone JH, Ytterberg SR, Merkel PA. Assessment of health-related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's). Arthritis Care Res (Hoboken). 2012 Feb;64(2):273-9. doi: 10.1002/acr.20649.

Reference Type: DERIVED

PMID: 21954229 (View on PubMed)

Related Links

http://rarediseasesnetwork.org/cms/vcrc/

Vasculitis Clinical Research Consortium

http://rarediseasesnetwork.org/

Rare Diseases Clinical Research Consortium

Other Identifiers

U54AR057319

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VCRC5505

Identifier Type: -

Identifier Source: org_study_id