<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/NCT03793270</url>
  </required_header>
  <id_info>
    <org_study_id>17200278</org_study_id>
    <nct_id>NCT03793270</nct_id>
  </id_info>
  <brief_title>Characterization of the Phenotypic Markers of B Cell Lymphocytes in Rheumatoid Arthritis</brief_title>
  <official_title>Characterization of the Phenotypic Markers of B Cell Lymphocytes in Rheumatoid Arthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assiut University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assiut University</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>
      Rheumatoid Arthritis (RA):&#xD;
&#xD;
      RA is a chronic inflammatory autoimmune disease that primarily affects the small joints,&#xD;
      eventually leading to bone erosion and an inability to move (1). Several immune cells&#xD;
      participate in the pathogenesis of RA. One of those cells is B cell.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      B cell population:&#xD;
&#xD;
      B lymphocytes play several critical roles in the pathogenesis of rheumatoid arthritis. They&#xD;
      are the source of the rheumatoid factors (RF) and anti-cyclic-citrullinated peptide&#xD;
      (anti-CCP), which contribute to immune complex formation and complement activation in the&#xD;
      joints (2).&#xD;
&#xD;
      There is different B cell subpopulation according to the stage of maturation and activity.&#xD;
      Distinction of this subpopulation can be done by detection of different CD molecules&#xD;
      expressed on cell surface (3). From all sub-population this research will focus on these&#xD;
      immunophenotypes; immature, mature, memory and B-reg cells by using CD 19, CD24, CD38 &amp; CD27&#xD;
      respectively.&#xD;
&#xD;
      Joa˜ o E. Fonseca and his team found the reduction in B cell subpopulation especially (Pre-&#xD;
      switched memory B cells) both in RA and Arthritis in the early stage. This observation not&#xD;
      related to using methotrexate or corticosteroid in the treatment. They used the&#xD;
      classification of B cells with CD 19 mainly and then IgD and CD27 to identify B cells (4).&#xD;
&#xD;
      Gabriella Sármay team found that the number of B-reg CD19+ CD27+ IL-10+ cells in peripheral&#xD;
      blood is fewer in RA patients compared with healthy controls (5).&#xD;
&#xD;
      Interleukin 10:&#xD;
&#xD;
      Interleukin (IL)-10 functions as an anti-inflammatory cytokine in rheumatoid arthritis. IL-10&#xD;
      mRNA levels were significantly elevated in synovial fluid mononuclear cells (SFMCs) from&#xD;
      patients with RA compared with PBMCs peripheral blood mononuclear cells (PBMCs) from RA&#xD;
      patients or healthy volunteers according to Isomäki P (6).&#xD;
&#xD;
      IL 10 is primarily produced by monocytes mainly and, then by lymphocytes; type 2 T helper&#xD;
      cells (TH2), mast cells, CD4+CD25+Foxp3+ regulatory T cells, and in a certain subset of&#xD;
      activated T cells and B cells (7).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 3, 2019</start_date>
  <completion_date type="Anticipated">August 20, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 20, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Detection of the percentage (%) B cell subpopulation in early-detected Rheumatic arthritis before taking long course medication and in late Rheumatic arthritis. Detection of the level of IL 10 in the serum for all patients.</measure>
    <time_frame>after 6 monthes</time_frame>
    <description>WBCs will be isolated from whole blood sample, then different monoclonal antibodies labeled with different markers will mixed with sample to be used for measuring the percent of each in the B cell population. Serum Samples will be collected and preserved in -80 degree then all samples will be measured with Elisa according to the manufacture procedures.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Autoimmune Diseases</condition>
  <arm_group>
    <arm_group_label>patients</arm_group_label>
    <description>1. Group 1: 30 diseased with Early Rheumatoid Arthritis from 6months to 1 year).&#xD;
drugs described in the clinic.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>patients 2</arm_group_label>
    <description>2. Group 2: 30 diseased with late/chronic Rheumatoid Arthritis. drugs described in the clinic.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy donors</arm_group_label>
    <description>3. Group 3: 30 healthy controls. No drugs.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>for patients and healthy donors</intervention_name>
    <description>Detection of (CD19, CD24, CD38 &amp; CD27) markers in peripheral blood samples by Flow Cytometry&#xD;
Determine the serum level of IL 10 using ELISA plate</description>
    <arm_group_label>healthy donors</arm_group_label>
    <arm_group_label>patients</arm_group_label>
    <arm_group_label>patients 2</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Total sample size will be 90 samples will be divided into groups:&#xD;
&#xD;
          1. Group 1: 30 diseased with Early Rheumatoid Arthritis from 6months to 1 year).&#xD;
&#xD;
          2. Group 2: 30 diseased with late/chronic Rheumatoid Arthritis.&#xD;
&#xD;
          3. Group 3: 30 healthy controls.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patient diagnosed as Rheumatoid arthritis that fulfilled ACR/EULAR Criteria (American&#xD;
             College of Rheumatology/European League Against Rheumatism).&#xD;
&#xD;
          -  (8) Age &gt;18 Years.&#xD;
&#xD;
             b. Exclusion criteria:&#xD;
&#xD;
          -  Diagnosed patients with other autoimmune disease or other infections.&#xD;
&#xD;
          -  Pregnant patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Khaled M Hasanein, Prof</last_name>
    <phone>01118508060</phone>
    <phone_ext>002</phone_ext>
    <email>khaledhassanein70@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mohamed S Badaery Ali, Prof</last_name>
    <phone>01000103328</phone>
    <phone_ext>002</phone_ext>
    <email>dtn_diatechnology@yahoo.com</email>
  </overall_contact_backup>
  <reference>
    <citation>Silverman GJ, Carson DA. Roles of B cells in rheumatoid arthritis. Arthritis Res Ther. 2003;5 Suppl 4(Suppl 4):S1-6. doi: 10.1186/ar1010. Epub 2003 Dec 2.</citation>
    <PMID>15180890</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 1, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>January 3, 2019</last_update_submitted>
  <last_update_submitted_qc>January 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Assiut University</investigator_affiliation>
    <investigator_full_name>Asmaa Rayan Mohammed</investigator_full_name>
    <investigator_title>Principle investigator</investigator_title>
  </responsible_party>
  <keyword>Rheumatoid arthritis RA - B cells (B Lymphocyte).</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
    <mesh_term>Autoimmune Diseases</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/NCT03793270
org study id: 17200278
nct id: NCT03793270
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Rheumatoid Arthritis (RA):

      RA is a chronic inflammatory autoimmune disease that primarily affects the small joints,
      eventually leading to bone erosion and an inability to move (1). Several immune cells
      participate in the pathogenesis of RA. One of those cells is B cell.
B cell population:

      B lymphocytes play several critical roles in the pathogenesis of rheumatoid arthritis. They
      are the source of the rheumatoid factors (RF) and anti-cyclic-citrullinated peptide
      (anti-CCP), which contribute to immune complex formation and complement activation in the
      joints (2).

      There is different B cell subpopulation according to the stage of maturation and activity.
      Distinction of this subpopulation can be done by detection of different CD molecules
      expressed on cell surface (3). From all sub-population this research will focus on these
      immunophenotypes; immature, mature, memory and B-reg cells by using CD 19, CD24, CD38 & CD27
      respectively.

      Joa˜ o E. Fonseca and his team found the reduction in B cell subpopulation especially (Pre-
      switched memory B cells) both in RA and Arthritis in the early stage. This observation not
      related to using methotrexate or corticosteroid in the treatment. They used the
      classification of B cells with CD 19 mainly and then IgD and CD27 to identify B cells (4).

      Gabriella Sármay team found that the number of B-reg CD19+ CD27+ IL-10+ cells in peripheral
      blood is fewer in RA patients compared with healthy controls (5).

      Interleukin 10:

      Interleukin (IL)-10 functions as an anti-inflammatory cytokine in rheumatoid arthritis. IL-10
      mRNA levels were significantly elevated in synovial fluid mononuclear cells (SFMCs) from
      patients with RA compared with PBMCs peripheral blood mononuclear cells (PBMCs) from RA
      patients or healthy volunteers according to Isomäki P (6).

      IL 10 is primarily produced by monocytes mainly and, then by lymphocytes; type 2 T helper
      cells (TH2), mast cells, CD4+CD25+Foxp3+ regulatory T cells, and in a certain subset of
      activated T cells and B cells (7).
observational model: Case-Control
time perspective: Cross-Sectional
measure: Detection of the percentage (%) B cell subpopulation in early-detected Rheumatic arthritis before taking long course medication and in late Rheumatic arthritis. Detection of the level of IL 10 in the serum for all patients.
time frame: after 6 monthes
description: WBCs will be isolated from whole blood sample, then different monoclonal antibodies labeled with different markers will mixed with sample to be used for measuring the percent of each in the B cell population. Serum Samples will be collected and preserved in -80 degree then all samples will be measured with Elisa according to the manufacture procedures.
arm group label: patients
description: 1. Group 1: 30 diseased with Early Rheumatoid Arthritis from 6months to 1 year).
drugs described in the clinic.
arm group label: patients 2
description: 2. Group 2: 30 diseased with late/chronic Rheumatoid Arthritis. drugs described in the clinic.
arm group label: healthy donors
description: 3. Group 3: 30 healthy controls. No drugs.
intervention type: Diagnostic Test
intervention name: for patients and healthy donors
description: Detection of (CD19, CD24, CD38 & CD27) markers in peripheral blood samples by Flow Cytometry
Determine the serum level of IL 10 using ELISA plate
arm group label: healthy donors
arm group label: patients
arm group label: patients 2
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Khaled M Hasanein, Prof
phone: 01118508060
phone ext: 002
email: khaledhassanein70@yahoo.com
last name: Mohamed S Badaery Ali, Prof
phone: 01000103328
phone ext: 002
email: dtn_diatechnology@yahoo.com
citation: Silverman GJ, Carson DA. Roles of B cells in rheumatoid arthritis. Arthritis Res Ther. 2003;5 Suppl 4(Suppl 4):S1-6. doi: 10.1186/ar1010. Epub 2003 Dec 2.
PMID: 15180890
responsible party type: Principal Investigator
investigator affiliation: Assiut University
investigator full name: Asmaa Rayan Mohammed
investigator title: Principle investigator
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Autoimmune Diseases
sharing ipd: No