One-Time DNA Study for Vasculitis

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Pennsylvania
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
Peter Merkel, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01241305
First received: October 22, 2010
Last updated: November 25, 2013
Last verified: November 2013
  Purpose

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
Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss)
Giant Cell Arteritis
Granulomatosis With Polyangiitis (Wegener's)
Microscopic Polyangiitis
Polyarteritis Nodosa
Takayasu's Arteritis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: VCRC Genetic Repository One-Time DNA Protocol

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Evaluation of clinical data and linked DNA specimens. [ Time Frame: 1 year. ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Two 10 ml tubes of blood will be collected for DNA extraction.


Estimated Enrollment: 1300
Study Start Date: October 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Individuals with giant cell arteritis, Takayasu's arteritis, polyarteritis nodosa, granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Enrollment will be sequential and patients will have disease in various stages and of different duration.

Criteria

Inclusion Criteria:

1. Diagnostic criteria for Giant Cell Arteritis Age at disease onset >50 years (required)

  1. New onset or new type of localized pain in the head
  2. Temporal artery abnormality (i.e. temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries)
  3. ESR of >40mm in the first hour by the Westergren method
  4. 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)
  5. Large Vessel Vasculitis (LVV) by angiogram or biopsy not explained by something else

Inclusion Criteria:

2. Diagnostic criteria for Takayasu's Arteritis

  1. Age at disease onset <50 years
  2. Claudication of extremities
  3. Decreased brachial artery pulse (one or both arteries)
  4. Blood pressure difference of >10mm Hg between the arms
  5. Bruit over subclavian arteries or aorta
  6. Arteriogram abnormalities compatible with TAK (includes conventional dye angiography or MR angiography or CT angiography)

Inclusion Criteria:

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

  1. Arteriographic abnormality
  2. Presence of granulocyte or mixed leukocyte infiltrate in an arterial wall on biopsy
  3. 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:

4. 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:

      5. Diagnostic criteria for Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss)

      1. Asthma
      2. Peak peripheral blood eosinophilia of >10% of total WBC
      3. Peripheral neuropathy attributable to vasculitis
      4. Transient pulmonary infiltrates on chest imaging studies
      5. Paranasal sinus abnormalities or nasal polyposis
      6. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241305

Contacts
Contact: Carol McAlear, MA cmcalear@upenn.edu

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Nadia Verde       Nadia.Verde@cshs.org   
Principal Investigator: Michael Weisman, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Ruby Harrison       rubyh@medicine.ucsf.edu;   
Principal Investigator: Sharon Chung, MD, MAS         
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 Monach, MD, PhD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Sara Biorn    507-284-4862    biorn.sara@mayo.edu   
Contact: Jane Jaquith    507-284-4502    jaquith.jane@mayo.edu   
Principal Investigator: Ulrich Specks, MD         
Principal Investigator: Steven Ytterberg, MD         
United States, New York
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Uzunma Udeh       udehu@hss.edu   
Principal Investigator: Robert Spiera, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Katie Gartner    216-445-1397    gartnek@ccf.org   
Principal Investigator: Carol Langford, MD, MHS         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Brian Rice       Brian.Rice@uphs.upenn.edu   
Principal Investigator: Peter Merkel, MD, MPH         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States
Contact: Dawn McBridge, RN       dlmc@imap.pitt.edu   
Principal Investigator: Larry Moreland, MD         
Canada, Ontario
St. Joseph's Healthcare Recruiting
Hamilton, Ontario, Canada
Contact: Sandra Messier    905-522-1155 ext 35873    smessier@stjoes.ca   
Principal Investigator: Nader Khalidi, MD         
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5T 3L9
Contact: Julia Farquharson    416-586-8616    JFarquharson@mtsinai.on.ca   
Principal Investigator: Simon Carette, MD         
Sponsors and Collaborators
University of Pennsylvania
Rare Diseases Clinical Research Network
Investigators
Study Director: Peter Merkel, MD, MPH University of Pennsylvania
  More Information

Additional Information:
No publications provided

Responsible Party: Peter Merkel, Professor, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01241305     History of Changes
Other Study ID Numbers: RDCRN 5510, U54AR057319-06
Study First Received: October 22, 2010
Last Updated: November 25, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
Vasculitis
CSS
EGPA
GCA
GPA
WG
MPA
PAN
TAK

Additional relevant MeSH terms:
Giant Cell Arteritis
Polymyalgia Rheumatica
Aortic Arch Syndromes
Arteritis
Churg-Strauss Syndrome
Microscopic Polyangiitis
Polyarteritis Nodosa
Systemic Vasculitis
Takayasu Arteritis
Wegener Granulomatosis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Aortic Diseases
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Connective Tissue Diseases
Granuloma
Immune System Diseases
Lung Diseases
Lung Diseases, Interstitial
Lymphatic Diseases
Lymphoproliferative Disorders
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 22, 2014