<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02257866</url>
  </required_header>
  <id_info>
    <org_study_id>140200</org_study_id>
    <secondary_id>14-AR-0200</secondary_id>
    <nct_id>NCT02257866</nct_id>
  </id_info>
  <brief_title>Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis</brief_title>
  <official_title>Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Vasculitis is a group of diseases that inflame and damage blood vessels and tissue. It can&#xD;
      cause many medical problems. Few tests can diagnose the disease, and none can reliably&#xD;
      predict a relapse. Researchers want to study people s genes and follow people over time to&#xD;
      see how the disease affects them.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      - To learn the signs, symptoms, imaging tests, genetic markers, and blood tests that can help&#xD;
      identify people with vasculitis and predict what will happen to them over time.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  People age 3 and older who have or are thought to have vasculitis, or are related to&#xD;
           someone with it.&#xD;
&#xD;
        -  Healthy volunteers.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be evaluated by a doctor who has expertise caring for patients with&#xD;
           vasculitis.&#xD;
&#xD;
        -  Participants will give a blood sample. Some will give a urine sample.&#xD;
&#xD;
        -  Some participants may have brushings or biopsies taken from the inside lining of the&#xD;
           nose.&#xD;
&#xD;
        -  Images of participants blood vessels may be taken using scans. For some scans,&#xD;
           participants will lie on a table that moves in and out of a cylinder that takes&#xD;
           pictures. For some scans, a contrast agent may be injected into an arm vein. Other scans&#xD;
           may use a radioactive form of sugar. Healthy minors will not have scans.&#xD;
&#xD;
        -  Some participants will answer questionnaires. - Some participants will have their tests&#xD;
           done at NIH. Others will have their doctor take the blood, saliva, or cheek swab samples&#xD;
           and send them to NIH.&#xD;
&#xD;
        -  Some participants will have one visit lasting 1-2 (but sometimes up to 4) days. Some&#xD;
           participants may have follow-up visits every 3 - 6 months, indefinitely.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this protocol is to study the natural history of idiopathic systemic&#xD;
      vasculitis in children and adults. The idiopathic vasculitides are a group of rare, systemic&#xD;
      diseases involving inflammation of arteries and other tissue with resulting organ- and&#xD;
      life-threatening disease courses. The different forms of idiopathic vasculitis are typically&#xD;
      classified based upon the predominant size of the arteries affected in each condition,&#xD;
      including small vessel vasculitis [granulomatosis with polyangiitis (GPA, Wegener s),&#xD;
      microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA,&#xD;
      Churg-Strauss)]; medium vessel vasculitis [polyarteritis nodosa (PAN)]; and large vessel&#xD;
      vasculitis [giant cell arteritis (GCA), Takayasu s arteritis (TAK), idiopathic aortitis&#xD;
      (IA)]. Although patients with each type of vasculitis manifest disease-specific aspects of&#xD;
      illness, there are substantial disease and treatment burdens common to patients with&#xD;
      vasculitis. For each type of idiopathic vasculitis, the disease course is often chronic,&#xD;
      relapse is common and unpredictable, organ and tissue damage can accrue over time, new&#xD;
      symptoms can occur late into the disease course, and treatment is often associated with&#xD;
      toxicity and serious side effects.&#xD;
&#xD;
      The goals of this natural history protocol are to establish a cohort of pediatric and adult&#xD;
      patients with vasculitis to prospectively evaluate the signs and symptoms, imaging findings,&#xD;
      and blood and tissue biomarkers associated with pathogenesis and disease outcomes. In the&#xD;
      small vessel vasculitides, where considerable progress has been made towards identifying&#xD;
      pathologic mechanisms of disease, we will focus on elucidating the pathogenic role of&#xD;
      neutrophils, selected biomarkers such as SERPINA1, and novel candidate biomarkers in&#xD;
      circulating blood and at local tissue sites including the nasal mucosa. In the medium and&#xD;
      large vessel vasculitides, we will identify novel candidate biomarkers for disease&#xD;
      pathogenesis and outcomes and develop disease activity indices that incorporate existing and&#xD;
      novel clinical, laboratory, genomic, and imaging biomarkers. For all types of vasculitis, a&#xD;
      goal of the protocol is to identify patients for possible entry into future treatment&#xD;
      studies.&#xD;
&#xD;
      Patients enrolled in this protocol will undergo a history, physical examination, and&#xD;
      laboratory evaluation. Since vasculitis is multi-system disease with variable patterns of&#xD;
      organ involvement, patients may undergo further comprehensive evaluation of a particular&#xD;
      affected organ system when clinically indicated. Peripheral blood samples will be collected&#xD;
      from affected patients, unrelated healthy volunteers matched for age, sex, and ethnicity&#xD;
      whenever possible, and in some cases unaffected family members to help identify and study the&#xD;
      genes involved in vasculitis and their functions. We may ask some patients to undergo nasal&#xD;
      biopsy and additional imaging studies for research purposes. For a small number of patients&#xD;
      and family members, we may ask permission to perform whole genome or exome sequencing.&#xD;
      Successful completion of these studies will improve our understanding of disease&#xD;
      pathogenesis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 29, 2014</start_date>
  <completion_date type="Anticipated">January 1, 2050</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2050</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>To study the pathogenesis of patients affected with idiopathic systemic vasculitis, including clinical, radiographic, immunological, and genetic characteristics of the disease</measure>
    <time_frame>end of study</time_frame>
    <description>To study the pathogenesis of patients affected with idiopathic systemic vasculitis, including clinical, radiographic, immunological, and genetic characteristics of the disease</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">4000</enrollment>
  <condition>Takayasu's Arteritis</condition>
  <condition>Giant Cell Arteritis</condition>
  <condition>Polyarteritis Nodosa</condition>
  <condition>Relapsing Polychondritis</condition>
  <condition>ANCA-Associated Vasculitis</condition>
  <arm_group>
    <arm_group_label>Healthy Volunteers</arm_group_label>
    <description>Patients without known auto immune diseases</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vasculitis</arm_group_label>
    <description>Patients with known or suspected vasculitis age 5 or older</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        idiopathic systemic vasculitis in children and adults&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
        SUBJECTS WITH VASCULITIS&#xD;
&#xD;
          -  Subjects who fulfill modified versions of the 1990 American College of Rheumatology&#xD;
             (ACR) Classification Criteria for GPA31 and PAN&#xD;
&#xD;
          -  Subjects who fulfill the 1990 ACR Classification Criteria for EGPA, GCA, and TAK&#xD;
&#xD;
          -  Subjects who fulfill the 2012 Chapel Hill Nomenclature definition for MPA&#xD;
&#xD;
          -  Subjects with other suspected systemic or single-organ vasculitides&#xD;
&#xD;
        HEALTHY VOLUNTEERS&#xD;
&#xD;
        -Volunteers able to provide consent, or in the case of minors, assent&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        SUBJECTS WITH VASCULITIS:&#xD;
&#xD;
          -  Subjects less than 3 years of age&#xD;
&#xD;
          -  Active malignancy, infection, or any medical condition that in the opinion of the&#xD;
             investigator would warrant exclusion&#xD;
&#xD;
          -  Inability to provide consent, or in the case of minors, assent&#xD;
&#xD;
          -  Subjects with bleeding diathesis or on anticoagulant medications (e.g. coumadin,&#xD;
             heparin, clopidogrel but not including aspirin or NSAIDs) are excluded from&#xD;
             participation in nasal brushing or biopsy studies&#xD;
&#xD;
        HEALTHY VOLUNTEERS&#xD;
&#xD;
          -  Volunteers less than 3 years of age&#xD;
&#xD;
          -  Diagnosis of vasculitis or other autoimmune/autoinflamamtory disease, including&#xD;
             systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, mixed connective&#xD;
             tissue disease or any overlap autoimmune syndrome&#xD;
&#xD;
          -  Active malignancy, infection, or any medical condition that in the opinion of the&#xD;
             investigator would warrant exclusion&#xD;
&#xD;
          -  Pregnant (by history of last menstrual period) or breast feeding subjects&#xD;
&#xD;
          -  Subjects with bleeding diathesis or taking anticoagulant medications (eg coumadin,&#xD;
             heparin, clopidogrel but not including aspirin or NSAIDs) are excluded from&#xD;
             participating in nasal brushing studies&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter C Grayson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wendy Goodspeed, R.N.</last_name>
    <phone>(301) 451-6761</phone>
    <email>goodspew@mail.nih.gov</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Peter C Grayson, M.D.</last_name>
    <phone>(301) 827-9187</phone>
    <email>peter.grayson@nih.gov</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)</last_name>
      <phone>800-411-1222</phone>
      <phone_ext>TTY dial 711</phone_ext>
      <email>ccopr@nih.gov</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2014-AR-0200.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Carmona-Rivera C, Purmalek MM, Moore E, Waldman M, Walter PJ, Garraffo HM, Phillips KA, Preston KL, Graf J, Kaplan MJ, Grayson PC. A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity. JCI Insight. 2017 Feb 9;2(3):e89780. doi: 10.1172/jci.insight.89780.</citation>
    <PMID>28194438</PMID>
  </reference>
  <reference>
    <citation>Grayson PC, Alehashemi S, Bagheri AA, Civelek AC, Cupps TR, Kaplan MJ, Malayeri AA, Merkel PA, Novakovich E, Bluemke DA, Ahlman MA. 18 F-Fluorodeoxyglucose-Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis. Arthritis Rheumatol. 2018 Mar;70(3):439-449. doi: 10.1002/art.40379. Epub 2018 Feb 6.</citation>
    <PMID>29145713</PMID>
  </reference>
  <reference>
    <citation>Quinn KA, Ahlman MA, Malayeri AA, Marko J, Civelek AC, Rosenblum JS, Bagheri AA, Merkel PA, Novakovich E, Grayson PC. Comparison of magnetic resonance angiography and 18F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis. Ann Rheum Dis. 2018 Aug;77(8):1165-1171. doi: 10.1136/annrheumdis-2018-213102. Epub 2018 Apr 17.</citation>
    <PMID>29666047</PMID>
  </reference>
  <verification_date>May 10, 2023</verification_date>
  <study_first_submitted>October 4, 2014</study_first_submitted>
  <study_first_submitted_qc>October 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>September 8, 2023</last_update_submitted>
  <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 11, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Polyarteritis Nodosa</keyword>
  <keyword>Takayasu's Arthritis</keyword>
  <keyword>Giant Cell Arthritis</keyword>
  <keyword>Relapsing Polychondritis</keyword>
  <keyword>Antineutrophil Cytoplasmic Antibodies</keyword>
  <keyword>Natural History</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polymyalgia Rheumatica</mesh_term>
    <mesh_term>Polychondritis, Relapsing</mesh_term>
    <mesh_term>Giant Cell Arteritis</mesh_term>
    <mesh_term>Vasculitis</mesh_term>
    <mesh_term>Arteritis</mesh_term>
    <mesh_term>Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis</mesh_term>
    <mesh_term>Takayasu Arteritis</mesh_term>
    <mesh_term>Aortic Arch Syndromes</mesh_term>
    <mesh_term>Systemic Vasculitis</mesh_term>
    <mesh_term>Polyarteritis Nodosa</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>.Protocol is silent about IPD sharing.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02257866
org study id: 140200
secondary id: 14-AR-0200
nct id: NCT02257866
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      - Vasculitis is a group of diseases that inflame and damage blood vessels and tissue. It can
      cause many medical problems. Few tests can diagnose the disease, and none can reliably
      predict a relapse. Researchers want to study people s genes and follow people over time to
      see how the disease affects them.

      Objective:

      - To learn the signs, symptoms, imaging tests, genetic markers, and blood tests that can help
      identify people with vasculitis and predict what will happen to them over time.

      Eligibility:

        -  People age 3 and older who have or are thought to have vasculitis, or are related to
           someone with it.

        -  Healthy volunteers.

      Design:

        -  Participants will be evaluated by a doctor who has expertise caring for patients with
           vasculitis.

        -  Participants will give a blood sample. Some will give a urine sample.

        -  Some participants may have brushings or biopsies taken from the inside lining of the
           nose.

        -  Images of participants blood vessels may be taken using scans. For some scans,
           participants will lie on a table that moves in and out of a cylinder that takes
           pictures. For some scans, a contrast agent may be injected into an arm vein. Other scans
           may use a radioactive form of sugar. Healthy minors will not have scans.

        -  Some participants will answer questionnaires. - Some participants will have their tests
           done at NIH. Others will have their doctor take the blood, saliva, or cheek swab samples
           and send them to NIH.

        -  Some participants will have one visit lasting 1-2 (but sometimes up to 4) days. Some
           participants may have follow-up visits every 3 - 6 months, indefinitely.
The purpose of this protocol is to study the natural history of idiopathic systemic
      vasculitis in children and adults. The idiopathic vasculitides are a group of rare, systemic
      diseases involving inflammation of arteries and other tissue with resulting organ- and
      life-threatening disease courses. The different forms of idiopathic vasculitis are typically
      classified based upon the predominant size of the arteries affected in each condition,
      including small vessel vasculitis [granulomatosis with polyangiitis (GPA, Wegener s),
      microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA,
      Churg-Strauss)]; medium vessel vasculitis [polyarteritis nodosa (PAN)]; and large vessel
      vasculitis [giant cell arteritis (GCA), Takayasu s arteritis (TAK), idiopathic aortitis
      (IA)]. Although patients with each type of vasculitis manifest disease-specific aspects of
      illness, there are substantial disease and treatment burdens common to patients with
      vasculitis. For each type of idiopathic vasculitis, the disease course is often chronic,
      relapse is common and unpredictable, organ and tissue damage can accrue over time, new
      symptoms can occur late into the disease course, and treatment is often associated with
      toxicity and serious side effects.

      The goals of this natural history protocol are to establish a cohort of pediatric and adult
      patients with vasculitis to prospectively evaluate the signs and symptoms, imaging findings,
      and blood and tissue biomarkers associated with pathogenesis and disease outcomes. In the
      small vessel vasculitides, where considerable progress has been made towards identifying
      pathologic mechanisms of disease, we will focus on elucidating the pathogenic role of
      neutrophils, selected biomarkers such as SERPINA1, and novel candidate biomarkers in
      circulating blood and at local tissue sites including the nasal mucosa. In the medium and
      large vessel vasculitides, we will identify novel candidate biomarkers for disease
      pathogenesis and outcomes and develop disease activity indices that incorporate existing and
      novel clinical, laboratory, genomic, and imaging biomarkers. For all types of vasculitis, a
      goal of the protocol is to identify patients for possible entry into future treatment
      studies.

      Patients enrolled in this protocol will undergo a history, physical examination, and
      laboratory evaluation. Since vasculitis is multi-system disease with variable patterns of
      organ involvement, patients may undergo further comprehensive evaluation of a particular
      affected organ system when clinically indicated. Peripheral blood samples will be collected
      from affected patients, unrelated healthy volunteers matched for age, sex, and ethnicity
      whenever possible, and in some cases unaffected family members to help identify and study the
      genes involved in vasculitis and their functions. We may ask some patients to undergo nasal
      biopsy and additional imaging studies for research purposes. For a small number of patients
      and family members, we may ask permission to perform whole genome or exome sequencing.
      Successful completion of these studies will improve our understanding of disease
      pathogenesis.
observational model: Cohort
time perspective: Prospective
measure: To study the pathogenesis of patients affected with idiopathic systemic vasculitis, including clinical, radiographic, immunological, and genetic characteristics of the disease
time frame: end of study
description: To study the pathogenesis of patients affected with idiopathic systemic vasculitis, including clinical, radiographic, immunological, and genetic characteristics of the disease
arm group label: Healthy Volunteers
description: Patients without known auto immune diseases
arm group label: Vasculitis
description: Patients with known or suspected vasculitis age 5 or older
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 3 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Peter C Grayson, M.D.
role: Principal Investigator
affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
last name: Wendy Goodspeed, R.N.
phone: (301) 451-6761
email: goodspew@mail.nih.gov
last name: Peter C Grayson, M.D.
phone: (301) 827-9187
email: peter.grayson@nih.gov
facility: 
status: Recruiting
contact: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2014-AR-0200.html
description: NIH Clinical Center Detailed Web Page
citation: Carmona-Rivera C, Purmalek MM, Moore E, Waldman M, Walter PJ, Garraffo HM, Phillips KA, Preston KL, Graf J, Kaplan MJ, Grayson PC. A role for muscarinic receptors in neutrophil extracellular trap formation and levamisole-induced autoimmunity. JCI Insight. 2017 Feb 9;2(3):e89780. doi: 10.1172/jci.insight.89780.
PMID: 28194438
citation: Grayson PC, Alehashemi S, Bagheri AA, Civelek AC, Cupps TR, Kaplan MJ, Malayeri AA, Merkel PA, Novakovich E, Bluemke DA, Ahlman MA. 18 F-Fluorodeoxyglucose-Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis. Arthritis Rheumatol. 2018 Mar;70(3):439-449. doi: 10.1002/art.40379. Epub 2018 Feb 6.
PMID: 29145713
citation: Quinn KA, Ahlman MA, Malayeri AA, Marko J, Civelek AC, Rosenblum JS, Bagheri AA, Merkel PA, Novakovich E, Grayson PC. Comparison of magnetic resonance angiography and 18F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis. Ann Rheum Dis. 2018 Aug;77(8):1165-1171. doi: 10.1136/annrheumdis-2018-213102. Epub 2018 Apr 17.
PMID: 29666047
responsible party type: Sponsor
mesh term: Polymyalgia Rheumatica
mesh term: Polychondritis, Relapsing
mesh term: Giant Cell Arteritis
mesh term: Vasculitis
mesh term: Arteritis
mesh term: Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
mesh term: Takayasu Arteritis
mesh term: Aortic Arch Syndromes
mesh term: Systemic Vasculitis
mesh term: Polyarteritis Nodosa
sharing ipd: Undecided
ipd description: .Protocol is silent about IPD sharing.