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

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
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

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Study Type :	Observational
Estimated Enrollment :	1200 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 :	April 2006
Estimated Primary Completion Date :	April 2019
Estimated Study Completion Date :	April 2019

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Biospecimen Retention:   Samples With DNA

Blood (serum and plasma), urine, and DNA

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Individuals with granulomatosis with polyangiitis (Wegener's)and microscopic polyangiitis. Enrollment will be sequential and participants will have disease in various stages and of different duration.

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

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Massachusetts
Boston University School of Medicine	Recruiting
Boston, Massachusetts, United States, 02118
Contact: Naomi Amudala, NP 617-414-2512 namudala@bu.edu
Principal Investigator: Paul A. Monach, MD, PhD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Sam Hughes Hughes.Samantha@mayo.edu
Principal Investigator: Ulrich Specks, MD
Principal Investigator: Steven R. Ytterberg, MD
United States, Ohio
Cleveland Clinic Foundation	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Elizabeth Kisela kiselae@ccf.org
Principal Investigator: Carol A. Langford, MD, MHS
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: B.Minal Hatwar Bhagyavati.Hatwar@uphs.upenn.edu
Principal Investigator: Peter Merkel, MD, MPH
University of Pittsburgh	Recruiting
Pittsburgh, Pennsylvania, United States, 15260
Contact: Laurie Hope hopelk@upmc.edu
Principal Investigator: Larry Moreland, MD
United States, Utah
University of Utah	Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Jessica Gonzalez jessica.gonzalez@hsc.utah.edu
Principal Investigator: Curry Koening, MD, MHS
Canada, Ontario
St. Joseph's Healthcare	Recruiting
Hamilton, Ontario, Canada
Contact: Sandra Messier 905-522-1155 ext 35873 smessier@stjoes.ca
Principal Investigator: Nader A. Khalidi, MD
Mount Sinai Hospital	Recruiting
Toronto, Ontario, Canada, M5T 3L9
Contact: Judy Vendramini judy.vendramini@sinaihealthsystem.ca
Principal Investigator: Simon Carette, MD

Sponsors and Collaborators

University of Pennsylvania

Office of Rare Diseases (ORD)

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

Rare Diseases Clinical Research Network

Investigators

Study Chair:	Peter A. Merkel, MD, MPH	University of Pennsylvania

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Vasculitis Clinical Research Consortium 

Rare Diseases Clinical Research Consortium 

Publications:

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.

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.

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

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

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Peter Merkel, Professor, University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00315393 History of Changes
Other Study ID Numbers:	VCRC5505; U54AR057319 ( U.S. NIH Grant/Contract )
First Posted:	April 18, 2006
Last Update Posted:	April 25, 2018
Last Verified:	April 2018

Keywords provided by Peter Merkel, University of Pennsylvania:

GPA; MPA; WG

Additional relevant MeSH terms:

Granulomatosis with Polyangiitis; Systemic Vasculitis; Microscopic Polyangiitis; Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases	Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases