<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/NCT03007134</url>
  </required_header>
  <id_info>
    <org_study_id>2008-1204</org_study_id>
    <secondary_id>RR019498</secondary_id>
    <nct_id>NCT03007134</nct_id>
  </id_info>
  <brief_title>Multicenter International Cross-Sectional Evaluation of Pulmonary Alveolar Proteinosis Trial</brief_title>
  <official_title>Multicenter International Cross-Sectional Evaluation of Pulmonary Alveolar Proteinosis Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rare Diseases Clinical Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Research Resources (NCRR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to (1) compare a technically improved assay with an existing&#xD;
      assay used to measure serum anti-GM-CSF antibodies in stored serum samples previously&#xD;
      obtained from patients diagnosed with either primary, secondary, congenital or idiopathic&#xD;
      pulmonary alveolar proteinosis (PAP), other chronic diseases or disease-free, healthy&#xD;
      individuals; (2) determine the prevalence and levels of anti-GM-CSF autoantibodies and (3)&#xD;
      define the breadth of the autoimmune antibody responses in primary PAP patients from the&#xD;
      United States, Japan, Australia, and Europe using previously collected serum samples; and (4)&#xD;
      using a chart review approach, compare the clinical, radiologic and laboratory features of&#xD;
      primary PAP patients to determine if differences exist among patients in these globally&#xD;
      geographically distributed regions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Rare Lung Disease Consortium (RLDC), a group of geographically-dispersed clinical&#xD;
      research sites, has been established to conduct collaborative clinical research regarding&#xD;
      rare lung diseases. The collaborative work includes diagnostic, therapeutic and other studies&#xD;
      in patients with pulmonary alveolar proteinosis (PAP), lymphangioleiomyomatosis (LAM),&#xD;
      alpha-1 antitrypsin deficiency (AATD), or hereditary interstitial lung diseases. These&#xD;
      patients can have delayed or incorrect diagnoses, and sub-optimal clinical management. The&#xD;
      present protocol is focused to individuals with PAP.&#xD;
&#xD;
      PAP occurs as primary, secondary, congenital and idiopathic forms. RLDC investigators have&#xD;
      previously shown that primary PAP is strongly associated with high levels of circulating,&#xD;
      neutralizing anti-GM-CSF autoantibodies. Absence of GM-CSF bioactivity is thought to impair&#xD;
      alveolar macrophage and blood neutrophil functions including reduced surfactant catabolism&#xD;
      (alveolar macrophages - thought to result in surfactant accumulation in primary PAP) and&#xD;
      immune dysfunction (neutrophil dysfunction, and possibly macrophage dysfunction - thought to&#xD;
      increase the risk of infection in primary PAP). Secondary PAP is caused by an underlying&#xD;
      condition believed to impair alveolar macrophage surfactant catabolism. Secondary PAP is&#xD;
      related to other conditions, including myelogenous leukemias, infections and environmental&#xD;
      exposures. Congenital PAP is caused by mutations in the genes encoding surfactant protein&#xD;
      (SP)-B, SP-C or the ABCA3 transporter. Idiopathic PAP is that which results from unknown&#xD;
      mechanisms. Anti-GM-CSF autoantibodies appear to be absent in secondary, congenital and&#xD;
      idiopathic PAP.&#xD;
&#xD;
      This cross sectional study protocol is designed to evaluate the autoimmune aspect of PAP in&#xD;
      patients that are currently being followed by clinical investigators in the Rare Lung Disease&#xD;
      Consortium (RLDC). The study involves a retrospective chart review and serological analysis&#xD;
      of preexisting, stored serum samples from individuals diagnosed with PAP. Thus, this study&#xD;
      will not involve any direct interactions or contact with PAP patients or any other study&#xD;
      participants. It will yield diagnostic information regarding the use of anti-granulocyte&#xD;
      macrophage-colony stimulating factor (GM-CSF) autoantibody testing in patients with PAP. It&#xD;
      will also yield information about the extent of the autoimmune response in primary PAP. In&#xD;
      addition, the study will compare/contrast the clinical phenotypes of individuals with&#xD;
      anti-GM-CSF autoantibody-positive PAP in various regions of the world. A stringent evaluation&#xD;
      of the autoimmune aspects of PAP including rigorous anti-GM-CSF antibody testing will provide&#xD;
      a better understanding of PAP and is expected to confirm the usefulness of serum anti-GM-CSF&#xD;
      antibody testing in the clinical diagnosis of PAP. The study will evaluate the rate of&#xD;
      serious or opportunistic infections and other clinical and demographic data from patients in&#xD;
      various regions of the world to determine if significant differences exist, which will&#xD;
      provide important knowledge regarding infectious and other complications associated with PAP.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2007</start_date>
  <completion_date type="Actual">July 2011</completion_date>
  <primary_completion_date type="Actual">July 2010</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Standardize the anti-GM-CSF autoantibody ELISA</measure>
    <time_frame>1 year</time_frame>
    <description>To compare a novel assay to an existing assay used to measure anti-GM-CSF autoantibodies in banked serum samples previously collected from individuals diagnosed with primary, secondary, congenital or idiopathic PAP, other chronic disorders, or disease-free, healthy individuals.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geographic distribution of anti-GM-CSF autoantibody levels</measure>
    <time_frame>1 years</time_frame>
    <description>GM-CSF autoantibody concentration in patients with autoimmune PAP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breadth of the autoimmune antibody phenotype of individuals with autoimmune PAP</measure>
    <time_frame>3 years</time_frame>
    <description>Autoimmune antibody phenotype of individuals with autoimmune PAP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Age of onset PAP symptoms</measure>
    <time_frame>2 years</time_frame>
    <description>Range of age at onset of symptoms of PAP among PAP patients from different global geographic regions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Age at the time of definitive PAP diagnosis</measure>
    <time_frame>2 years</time_frame>
    <description>Range of age at the time of definitive pathologic diagnosis of PAP among PAP patients from different global geographic regions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of time from onset of symptoms and definitive diagnosis of autoimmune PAP</measure>
    <time_frame>2 years</time_frame>
    <description>Length of time between the onset of symptoms and a definitive pathologic diagnosis of PAP among PAP patients from different global geographic regions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gender distribution among PAP patients</measure>
    <time_frame>2 years</time_frame>
    <description>Gender distribution among PAP patients from different global geographic regions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tobacco use among PAP patients</measure>
    <time_frame>2 years</time_frame>
    <description>Variability of tobacco use among PAP patients from different global geographic regions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major medical history comparison among PAP patients</measure>
    <time_frame>2 years</time_frame>
    <description>Variability of associated major medical diagnoses among PAP patients from different global geographic regions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease severity variability among autoimmune PAP patients from various geographic locations</measure>
    <time_frame>2 years</time_frame>
    <description>Severity of the disease at onset among PAP patients from different global geographic regions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of secondary infections that occur in patients with primary PAP</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants documented to have had a secondary infection(s)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type of secondary infections that occur in patients with primary PAP</measure>
    <time_frame>2 years</time_frame>
    <description>List the specific organisms documented to have infected PAP patients</description>
  </secondary_outcome>
  <enrollment type="Actual">73</enrollment>
  <condition>Pulmonary Alveolar Proteinosis</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Retrospective Chart Review</intervention_name>
    <description>No intervention.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Autoimmune PAP&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Data and Serum must be from individuals of any age with confirmed diagnosis of PAP based on&#xD;
        the following criteria:&#xD;
&#xD;
          -  Radiographic features consistent with PAP&#xD;
&#xD;
          -  Pathological or cytological findings consistent with PAP determined by either open&#xD;
             lung biopsy, transbronchial biopsy or bronchoalveolar lavage cell/fluid cytology.&#xD;
&#xD;
          -  Elevated anti-GM-CSF autoantibody concentration, when available&#xD;
&#xD;
        Ability of the international PI's and their research coordinators to ship samples in&#xD;
        compliance with this study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No established diagnosis of PAP&#xD;
&#xD;
          -  Incomplete chart records in which &gt;25% of the requested data is unable to be&#xD;
             confirmed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce Trapnell</last_name>
    <role>Study Chair</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brody School of Medicine</name>
      <address>
        <city>Greenville</city>
        <state>North Carolina</state>
        <zip>27834</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ruhrlandklinik Essen</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Malattie Apparato Respiratorio Università di Pavia</name>
      <address>
        <city>Pavia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Niigata Medical and Dental School</name>
      <address>
        <city>Niigata</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHO Kinki-Chuo Chest Center</name>
      <address>
        <city>Osaka</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>December 29, 2016</last_update_submitted>
  <last_update_submitted_qc>December 29, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Alveolar Proteinosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03007134
org study id: 2008-1204
secondary id: RR019498
nct id: NCT03007134
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to (1) compare a technically improved assay with an existing
      assay used to measure serum anti-GM-CSF antibodies in stored serum samples previously
      obtained from patients diagnosed with either primary, secondary, congenital or idiopathic
      pulmonary alveolar proteinosis (PAP), other chronic diseases or disease-free, healthy
      individuals; (2) determine the prevalence and levels of anti-GM-CSF autoantibodies and (3)
      define the breadth of the autoimmune antibody responses in primary PAP patients from the
      United States, Japan, Australia, and Europe using previously collected serum samples; and (4)
      using a chart review approach, compare the clinical, radiologic and laboratory features of
      primary PAP patients to determine if differences exist among patients in these globally
      geographically distributed regions.
The Rare Lung Disease Consortium (RLDC), a group of geographically-dispersed clinical
      research sites, has been established to conduct collaborative clinical research regarding
      rare lung diseases. The collaborative work includes diagnostic, therapeutic and other studies
      in patients with pulmonary alveolar proteinosis (PAP), lymphangioleiomyomatosis (LAM),
      alpha-1 antitrypsin deficiency (AATD), or hereditary interstitial lung diseases. These
      patients can have delayed or incorrect diagnoses, and sub-optimal clinical management. The
      present protocol is focused to individuals with PAP.

      PAP occurs as primary, secondary, congenital and idiopathic forms. RLDC investigators have
      previously shown that primary PAP is strongly associated with high levels of circulating,
      neutralizing anti-GM-CSF autoantibodies. Absence of GM-CSF bioactivity is thought to impair
      alveolar macrophage and blood neutrophil functions including reduced surfactant catabolism
      (alveolar macrophages - thought to result in surfactant accumulation in primary PAP) and
      immune dysfunction (neutrophil dysfunction, and possibly macrophage dysfunction - thought to
      increase the risk of infection in primary PAP). Secondary PAP is caused by an underlying
      condition believed to impair alveolar macrophage surfactant catabolism. Secondary PAP is
      related to other conditions, including myelogenous leukemias, infections and environmental
      exposures. Congenital PAP is caused by mutations in the genes encoding surfactant protein
      (SP)-B, SP-C or the ABCA3 transporter. Idiopathic PAP is that which results from unknown
      mechanisms. Anti-GM-CSF autoantibodies appear to be absent in secondary, congenital and
      idiopathic PAP.

      This cross sectional study protocol is designed to evaluate the autoimmune aspect of PAP in
      patients that are currently being followed by clinical investigators in the Rare Lung Disease
      Consortium (RLDC). The study involves a retrospective chart review and serological analysis
      of preexisting, stored serum samples from individuals diagnosed with PAP. Thus, this study
      will not involve any direct interactions or contact with PAP patients or any other study
      participants. It will yield diagnostic information regarding the use of anti-granulocyte
      macrophage-colony stimulating factor (GM-CSF) autoantibody testing in patients with PAP. It
      will also yield information about the extent of the autoimmune response in primary PAP. In
      addition, the study will compare/contrast the clinical phenotypes of individuals with
      anti-GM-CSF autoantibody-positive PAP in various regions of the world. A stringent evaluation
      of the autoimmune aspects of PAP including rigorous anti-GM-CSF antibody testing will provide
      a better understanding of PAP and is expected to confirm the usefulness of serum anti-GM-CSF
      antibody testing in the clinical diagnosis of PAP. The study will evaluate the rate of
      serious or opportunistic infections and other clinical and demographic data from patients in
      various regions of the world to determine if significant differences exist, which will
      provide important knowledge regarding infectious and other complications associated with PAP.
observational model: Cohort
time perspective: Retrospective
measure: Standardize the anti-GM-CSF autoantibody ELISA
time frame: 1 year
description: To compare a novel assay to an existing assay used to measure anti-GM-CSF autoantibodies in banked serum samples previously collected from individuals diagnosed with primary, secondary, congenital or idiopathic PAP, other chronic disorders, or disease-free, healthy individuals.
measure: Geographic distribution of anti-GM-CSF autoantibody levels
time frame: 1 years
description: GM-CSF autoantibody concentration in patients with autoimmune PAP
measure: Breadth of the autoimmune antibody phenotype of individuals with autoimmune PAP
time frame: 3 years
description: Autoimmune antibody phenotype of individuals with autoimmune PAP
measure: Age of onset PAP symptoms
time frame: 2 years
description: Range of age at onset of symptoms of PAP among PAP patients from different global geographic regions
measure: Age at the time of definitive PAP diagnosis
time frame: 2 years
description: Range of age at the time of definitive pathologic diagnosis of PAP among PAP patients from different global geographic regions
measure: Length of time from onset of symptoms and definitive diagnosis of autoimmune PAP
time frame: 2 years
description: Length of time between the onset of symptoms and a definitive pathologic diagnosis of PAP among PAP patients from different global geographic regions
measure: Gender distribution among PAP patients
time frame: 2 years
description: Gender distribution among PAP patients from different global geographic regions
measure: Tobacco use among PAP patients
time frame: 2 years
description: Variability of tobacco use among PAP patients from different global geographic regions
measure: Major medical history comparison among PAP patients
time frame: 2 years
description: Variability of associated major medical diagnoses among PAP patients from different global geographic regions
measure: Disease severity variability among autoimmune PAP patients from various geographic locations
time frame: 2 years
description: Severity of the disease at onset among PAP patients from different global geographic regions
measure: Number of secondary infections that occur in patients with primary PAP
time frame: 2 years
description: Number of participants documented to have had a secondary infection(s)
measure: Type of secondary infections that occur in patients with primary PAP
time frame: 2 years
description: List the specific organisms documented to have infected PAP patients
intervention type: Other
intervention name: Retrospective Chart Review
description: No intervention.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Bruce Trapnell
role: Study Chair
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Italy
country: Japan
country: United States
responsible party type: Sponsor
mesh term: Pulmonary Alveolar Proteinosis
sharing ipd: No