One-Time DNA Study for Vasculitis

Sponsor

University of Pennsylvania (Other)

Overall Status

Recruiting

CT.gov ID

NCT01241305

Collaborator

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

1,000

Enrollment

Locations

202

Duration (Months)

71.4

Patients Per Site

0.4

Patients Per Site Per Month

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.

Condition or Disease	Intervention/Treatment	Phase
Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss) Giant Cell Arteritis Granulomatosis With Polyangiitis (Wegener's) Microscopic Polyangiitis Polyarteritis Nodosa Takayasu's Arteritis

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:

Observational

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnostic criteria for Giant Cell Arteritis Age at disease onset >50 years (required)
New onset or new type of localized pain in the head
Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries)
ESR of >40mm in the first hour by the Westergren method
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)
Large Vessel Vasculitis (LVV) by angiogram or biopsy not explained by something else

Inclusion Criteria:

Diagnostic criteria for Takayasu's Arteritis
Age at disease onset <50 years
Claudication of extremities
Decreased brachial artery pulse (one or both arteries)
Blood pressure difference of >10mm Hg between the arms
Bruit over subclavian arteries or aorta
Arteriogram abnormalities compatible with TAK (includes conventional dye angiography or MR angiography or CT angiography)

Inclusion Criteria:

Diagnostic criteria for Polyarteritis Nodosa Major criteria (not explained by other causes) felt by investigator to be due to vasculitis
Arteriographic abnormality
Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy
Mononeuropathy or polyneuropathy

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

Weight loss > 4 kg
Livedo reticularis, cutaneous ulcerations, or skin nodules
Testicular pain or tenderness
Myalgias
Diastolic blood pressure > 90 mm Hg
Elevated BUN or serum creatinine levels
Ischemic abdominal pain

Isolated cutaneous Polyarteritis Nodosa 1. Biopsy-proven cutaneous PAN

Inclusion Criteria:

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:

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

Inclusion Criteria:

Diagnostic criteria for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss)
Asthma
Peak peripheral blood eosinophilia of >10% of total WBC
Peripheral neuropathy attributable to vasculitis
Transient pulmonary infiltrates on chest imaging studies
Paranasal sinus abnormalities or nasal polyposis
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

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