<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/NCT02229448</url>
  </required_header>
  <id_info>
    <org_study_id>IgG4-RD diagnosis</org_study_id>
    <nct_id>NCT02229448</nct_id>
  </id_info>
  <brief_title>Retrospective Study for Diagnosis of Undetected IgG4 Related Diseases in Patients With High Serum IgG4 Levels.</brief_title>
  <official_title>A Survey of Patients With Elevated Serum IGG4 With Unknown IGG4-related Disease to Whom Biopsy and Performance of Subsequent Specific Staining for Clinical, Laboratory and Pathologic Correlation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Meir Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Meir Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome of unknown&#xD;
      etiology comprised of a collection of disorders that share specific pathologic, serologic,&#xD;
      and clinical features.&#xD;
&#xD;
      Histopathological analysis of biopsy specimens remains the cornerstone in the diagnosis of&#xD;
      IgG4- related disease. Elevated concentrations of IgG4 in tissue and serum are helpful in&#xD;
      diagnosing IgG4-related disease, but neither one is a specific diagnostic marker. Correlation&#xD;
      with specific histopathological findings is essential, regardless of the serum IgG4&#xD;
      concentration, the number of IgG4-positive plasma cells in tissue, or the ratio of IgG4 to&#xD;
      IgG in tissue. Misdiagnoses of IgG4-related disease are increasingly common because of&#xD;
      excessive emphasis on moderate elevations of serum IgG4 concentration and overreliance on the&#xD;
      finding of IgG4-positive plasma cells in tissue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      IgG4 is a unique antibody in both structure and function. This molecule accounts for less&#xD;
      than 5% of the total IgG in healthy persons and is the least abundant IgG subclass. In&#xD;
      contrast to IgG1, IgG2, and IgG3, serum IgG4 concentrations among ostensibly healthy people&#xD;
      vary by a factor of more than 100 (normal range, 0.01 to 1.4 mg per milliliter), but IgG4&#xD;
      concentrations within individual persons are generally stable.&#xD;
&#xD;
      Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome of unknown&#xD;
      etiology comprised of a collection of disorders that share specific pathologic, serologic,&#xD;
      and clinical features.&#xD;
&#xD;
      These different conditions were previously thought to be unrelated [2-4]. The commonly shared&#xD;
      features include tumor-like swelling of involved organs, a lymphoplasmacytic infiltrate&#xD;
      enriched in IgG4-positive plasma cells, and variable degrees of fibrosis that has a&#xD;
      characteristic &quot;storiform&quot; pattern. In addition, elevated serum concentrations of IgG4 are&#xD;
      found in 60 to 70 percent of patients with IgG4-RD.&#xD;
&#xD;
      Two major presentations of this condition, which often affects more than one organ, are type&#xD;
      1 autoimmune pancreatitis (IgG4-related pancreatitis) and salivary gland disease; the later&#xD;
      may present as salivary gland enlargement or as sclerosing sialadenitis (formerly termed&#xD;
      &quot;Mikulicz disease&quot; and Küttner's tumor, respectively). These conditions often resemble&#xD;
      Sjögren's syndrome but are pathophysiologically distinct from this disorder. The preferred&#xD;
      name for the overall condition is IgG4-related disease.&#xD;
&#xD;
      The presence of IgG4-bearing plasma cells is required for a diagnosis of IgG4- related&#xD;
      disease, but IgG4-positive cells are found in a wide variety of inflammatory infiltrates, and&#xD;
      the detection of substantial numbers of IgG4- positive plasma cells is therefore not&#xD;
      diagnostic of IgG4-related disease.&#xD;
&#xD;
      Tissues from patients with IgG4-related disease show diffuse infiltrates of IgG4-bearing&#xD;
      plasma cells, in contrast to the focal aggregates of IgG4-bearing cells that are detected in&#xD;
      most other inflammatory mimickers of this condition. A diffuse plasma-cell infiltrate with&#xD;
      more than 30 IgG4-positive cells per high power field and a ratio of IgG4 to IgG that is&#xD;
      higher than 50% provides compelling evidence of IgG4-related disease.&#xD;
&#xD;
      The study will examine the clinical data from the computerized database of Meir Hospital for&#xD;
      patient with unknown IGG4-related disease with high serum levels of IGG4 that were admitted&#xD;
      for hospitalization for any reason in a period of 14 years, from January 2000 to June 2014.&#xD;
&#xD;
      Since biopsy has proven to be the hallmark in diagnosing IGG4 RD, we decided to complete the&#xD;
      investigation in a pool of patients to whom high IGG4 serum levels where confirmed and to&#xD;
      whom biopsies from any suitable tissue where obtained for other reasons than IGG4 RD and then&#xD;
      to perform specific staining for IGG4 to those samples, by sending them back to the pathology&#xD;
      service at our hospital.&#xD;
&#xD;
      Furthermore clinical and other laboratory features of each positive patient will then be&#xD;
      correlated from the history of admission of each patient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>serum level of IGG4</measure>
    <time_frame>6 months</time_frame>
    <description>Taken from a computerized database</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>specific staining for IGG4 to biopsy samples</measure>
    <time_frame>six months</time_frame>
    <description>took from biposy that save for clinical trails</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">11</enrollment>
  <condition>Undiagnosed IgG4 Related Diseases</condition>
  <arm_group>
    <arm_group_label>IgG4 UKN diagnosis</arm_group_label>
    <description>who ever been found with IgG4 sub class in blood sample or in his byposy</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        All patients that where admitted during the period of January 2000 to June 2014 at MEIR&#xD;
        HOSPITAL- KFAR SABA from all ages, from all parts of Israel, all races will be included,&#xD;
        from both genders.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients that where admitted during the period of January 2000 to June 2014 at&#xD;
             MEIR HOSPITAL KFAR SAVA, with at least one result of a high serum level of IGG4&#xD;
             according to the accepted normal range in our laboratory (more than 100mg/dL) and to&#xD;
             whom biopsy of a suitable tissue was obtained for other reasons than IGG4 Related&#xD;
             Diseases.&#xD;
&#xD;
          -  Both genders will be included.&#xD;
&#xD;
          -  Patients of all ages.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have already been diagnosed with IGG4-Related Diseases.&#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>Yair Levy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Meir Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shalabi Khaled</last_name>
    <role>Study Chair</role>
    <affiliation>Meir Medical Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Evgeny Edelshtein, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Meir Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Meir Medical Center</name>
      <address>
        <city>Kfar-Saba</city>
        <zip>44281</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>November 15, 2017</last_update_submitted>
  <last_update_submitted_qc>November 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Meir Medical Center</investigator_affiliation>
    <investigator_full_name>yair levy</investigator_full_name>
    <investigator_title>Meir Medical Center</investigator_title>
  </responsible_party>
  <keyword>Immunoglobulin G</keyword>
  <keyword>focus</keyword>
  <keyword>study</keyword>
  <keyword>detect</keyword>
  <keyword>patients</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulin G4-Related Disease</mesh_term>
  </condition_browse>
  <!-- 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/NCT02229448
org study id: IgG4-RD diagnosis
nct id: NCT02229448
lead sponsor: 
has dmc: No
Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome of unknown
      etiology comprised of a collection of disorders that share specific pathologic, serologic,
      and clinical features.

      Histopathological analysis of biopsy specimens remains the cornerstone in the diagnosis of
      IgG4- related disease. Elevated concentrations of IgG4 in tissue and serum are helpful in
      diagnosing IgG4-related disease, but neither one is a specific diagnostic marker. Correlation
      with specific histopathological findings is essential, regardless of the serum IgG4
      concentration, the number of IgG4-positive plasma cells in tissue, or the ratio of IgG4 to
      IgG in tissue. Misdiagnoses of IgG4-related disease are increasingly common because of
      excessive emphasis on moderate elevations of serum IgG4 concentration and overreliance on the
      finding of IgG4-positive plasma cells in tissue.
IgG4 is a unique antibody in both structure and function. This molecule accounts for less
      than 5% of the total IgG in healthy persons and is the least abundant IgG subclass. In
      contrast to IgG1, IgG2, and IgG3, serum IgG4 concentrations among ostensibly healthy people
      vary by a factor of more than 100 (normal range, 0.01 to 1.4 mg per milliliter), but IgG4
      concentrations within individual persons are generally stable.

      Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome of unknown
      etiology comprised of a collection of disorders that share specific pathologic, serologic,
      and clinical features.

      These different conditions were previously thought to be unrelated [2-4]. The commonly shared
      features include tumor-like swelling of involved organs, a lymphoplasmacytic infiltrate
      enriched in IgG4-positive plasma cells, and variable degrees of fibrosis that has a
      characteristic "storiform" pattern. In addition, elevated serum concentrations of IgG4 are
      found in 60 to 70 percent of patients with IgG4-RD.

      Two major presentations of this condition, which often affects more than one organ, are type
      1 autoimmune pancreatitis (IgG4-related pancreatitis) and salivary gland disease; the later
      may present as salivary gland enlargement or as sclerosing sialadenitis (formerly termed
      "Mikulicz disease" and Küttner's tumor, respectively). These conditions often resemble
      Sjögren's syndrome but are pathophysiologically distinct from this disorder. The preferred
      name for the overall condition is IgG4-related disease.

      The presence of IgG4-bearing plasma cells is required for a diagnosis of IgG4- related
      disease, but IgG4-positive cells are found in a wide variety of inflammatory infiltrates, and
      the detection of substantial numbers of IgG4- positive plasma cells is therefore not
      diagnostic of IgG4-related disease.

      Tissues from patients with IgG4-related disease show diffuse infiltrates of IgG4-bearing
      plasma cells, in contrast to the focal aggregates of IgG4-bearing cells that are detected in
      most other inflammatory mimickers of this condition. A diffuse plasma-cell infiltrate with
      more than 30 IgG4-positive cells per high power field and a ratio of IgG4 to IgG that is
      higher than 50% provides compelling evidence of IgG4-related disease.

      The study will examine the clinical data from the computerized database of Meir Hospital for
      patient with unknown IGG4-related disease with high serum levels of IGG4 that were admitted
      for hospitalization for any reason in a period of 14 years, from January 2000 to June 2014.

      Since biopsy has proven to be the hallmark in diagnosing IGG4 RD, we decided to complete the
      investigation in a pool of patients to whom high IGG4 serum levels where confirmed and to
      whom biopsies from any suitable tissue where obtained for other reasons than IGG4 RD and then
      to perform specific staining for IGG4 to those samples, by sending them back to the pathology
      service at our hospital.

      Furthermore clinical and other laboratory features of each positive patient will then be
      correlated from the history of admission of each patient.
observational model: Case-Only
time perspective: Retrospective
measure: serum level of IGG4
time frame: 6 months
description: Taken from a computerized database
measure: specific staining for IGG4 to biopsy samples
time frame: six months
description: took from biposy that save for clinical trails
arm group label: IgG4 UKN diagnosis
description: who ever been found with IgG4 sub class in blood sample or in his byposy
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Yair Levy, MD
role: Principal Investigator
affiliation: Meir Medical Center
last name: Shalabi Khaled
role: Study Chair
affiliation: Meir Medical Center
last name: Evgeny Edelshtein, MD
role: Study Chair
affiliation: Meir Medical Center
facility: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Meir Medical Center
investigator full name: yair levy
investigator title: Meir Medical Center
mesh term: Immunoglobulin G4-Related Disease