One-Time DNA Study for Vasculitis

University of Pennsylvania (Other)
Overall Status
Recruiting ID
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH), Office of Rare Diseases (ORD) (NIH), Rare Diseases Clinical Research Network (Other)

Study Details

Study Description

Brief Summary

The purpose of this study is to identify genes that increase the risk of developing vasculitis, a group of severe diseases that feature inflammation of blood vessels. Results of these studies will provide vasculitis researchers with insight into the causes of these diseases and generate new ideas for diagnostic tests and therapies, and will be of great interest to the larger communities of researchers investigating vasculitis and other autoimmune, inflammatory, and vascular diseases.

Detailed Description

The systemic vasculitides comprise several inflammatory diseases of blood vessels, usually arteries, which may cause systemic, multi-organ disease that can result in substantial morbidity and increased mortality. Each type of vasculitis is a rare ("orphan") disease. However, taken together, vasculitis affects tens of thousands of Americans and is responsible for substantial morbidity and mortality and almost one billion dollars per year in hospital care alone. While the vasculitides share the trait of vascular inflammation, the unique disease phenotypes, clinical courses, differences in prognoses, and responses to therapy suggest that important differences exist in pathogenesis. The Vasculitis Clinical Research Consortium (VCRC) currently focuses on 6 specific types of vasculitis that were selected to represent a balance between unmet medical and scientific needs, prevalence in North America, feasibility of study, and an interest in studying a spectrum of small, medium, and large vessel vasculitides.

The great majority of published studies on the genetics of vasculitis have used modest-sized cohorts that are only suitable for investigation of a few candidate genes at a time, or to detect large effect sizes, so that replicated findings are highly skewed to the HLA region. Larger and more ambitious genetic studies in vasculitis are expected to generate numerous hypotheses for translational research in gene expression, biochemistry, and molecular pathology.

A one-time collection of clinical data and DNA would substantially increase the sample sizes for genetic association studies in all six vasculitides studied in the VCRC. Many patients are seen at participating VCRC centers but do not enroll in the Longitudinal Studies. These patients often are interested in participating in research studies but cannot return frequently for visits, usually due to distance from the VCRC centers. This approach would be particularly useful for the rarer forms of vasculitis under study (Takayasu's Arteritis (TAK), Polyarteritis Nodosa (PAN), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) and also for Giant Cell Arteritis (GCA), since elderly patients have been particularly likely to decline participation in the Longitudinal Studies due to travel constraints.

Study Design

Study Type:
Anticipated Enrollment :
1000 participants
Observational Model:
Time Perspective:
Official Title:
VCRC Genetic Repository One-Time DNA Protocol
Study Start Date :
Oct 1, 2010
Anticipated Primary Completion Date :
Aug 1, 2027
Anticipated Study Completion Date :
Aug 1, 2027

Outcome Measures

Primary Outcome Measures

  1. Evaluation of clinical data and linked DNA specimens. [1 year.]

Eligibility Criteria


Ages Eligible for Study:
7 Years and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Inclusion Criteria:
  1. Diagnostic criteria for Giant Cell Arteritis Age at disease onset >50 years (required)

  2. New onset or new type of localized pain in the head

  3. Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries)

  4. ESR of >40mm in the first hour by the Westergren method

  5. Abnormal artery biopsy (i.e. temporal artery biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells)

  6. Large Vessel Vasculitis (LVV) by angiogram or biopsy not explained by something else

Inclusion Criteria:
  1. Diagnostic criteria for Takayasu's Arteritis

  2. Age at disease onset <50 years

  3. Claudication of extremities

  4. Decreased brachial artery pulse (one or both arteries)

  5. Blood pressure difference of >10mm Hg between the arms

  6. Bruit over subclavian arteries or aorta

  7. Arteriogram abnormalities compatible with TAK (includes conventional dye angiography or MR angiography or CT angiography)

Inclusion Criteria:
  1. Diagnostic criteria for Polyarteritis Nodosa Major criteria (not explained by other causes) felt by investigator to be due to vasculitis

  2. Arteriographic abnormality

  3. Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy

  4. Mononeuropathy or polyneuropathy

Minor criteria (not explained by other causes) felt by investigator to be due to vasculitis

  1. Weight loss > 4 kg

  2. Livedo reticularis, cutaneous ulcerations, or skin nodules

  3. Testicular pain or tenderness

  4. Myalgias

  5. Diastolic blood pressure > 90 mm Hg

  6. Elevated BUN or serum creatinine levels

  7. Ischemic abdominal pain

Isolated cutaneous Polyarteritis Nodosa 1. Biopsy-proven cutaneous PAN

Inclusion Criteria:
  1. Diagnostic criteria for Granulomatosis with Polyangiitis (Wegener's) (GPA) and Microscopic Polyangitis (MPA)
  • Diagnosis of GPA or MPA. Widely accepted diagnostic criteria, as opposed to classification criteria or definitions, have not been developed for GPA & MPA.

  • For diagnosis of GPA meets at least 2 of the following 5 modified 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

Inclusion Criteria:
  1. Diagnostic criteria for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss)

  2. Asthma

  3. Peak peripheral blood eosinophilia of >10% of total WBC

  4. Peripheral neuropathy attributable to vasculitis

  5. Transient pulmonary infiltrates on chest imaging studies

  6. Paranasal sinus abnormalities or nasal polyposis

  7. Eosinophilic inflammation on tissue biopsy

If patients have 4 of the above 6 criteria but lack clearcut documentation of small vessel vasculitis, they are also eligible for enrollment.

General Exclusion Criteria:
  • Inability to give informed consent and to sign the consent form

  • Enrolled in VCRC protocols 5502, 5503, 5504, 5505, 5506, 5522, or 5523

  • Unwilling to provide blood for DNA collection

Contacts and Locations


Site City State Country Postal Code
1 Cedars-Sinai Medical Center Los Angeles California United States 90048
2 University of California, San Francisco San Francisco California United States 94143
3 Northwestern University Chicago Illinois United States 60208
4 University of Kansas Medical Center Kansas City Kansas United States 66103
5 University of Michigan Ann Arbor Michigan United States 48109-5422
6 Mayo Clinic Rochester Minnesota United States 55905
7 Hospital for Special Surgery New York New York United States 10021
8 Cleveland Clinic Cleveland Ohio United States 44195
9 University of Pennsylvania Philadelphia Pennsylvania United States 19104
10 University of Pittsburgh Pittsburgh Pennsylvania United States 15261
11 University of Utah Salt Lake City Utah United States 84132
12 St. Joseph's Healthcare Hamilton Ontario Canada
13 Mount Sinai Hospital Toronto Ontario Canada M5T 3L9
14 Istanbul University Istanbul Fatih Turkey 34452

Sponsors and Collaborators

  • University of Pennsylvania
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • Office of Rare Diseases (ORD)
  • Rare Diseases Clinical Research Network


  • Study Director: Peter Merkel, MD, MPH, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Additional Information:


None provided.
Responsible Party:
Peter Merkel, Professor, University of Pennsylvania Identifier:
Other Study ID Numbers:
  • VCRC5510
  • U54AR057319-06
First Posted:
Nov 16, 2010
Last Update Posted:
May 17, 2022
Last Verified:
May 1, 2022

Study Results

No Results Posted as of May 17, 2022