<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/NCT04472481</url>
  </required_header>
  <id_info>
    <org_study_id>33846</org_study_id>
    <nct_id>NCT04472481</nct_id>
  </id_info>
  <brief_title>Vitamin D Effect in Rheumatoid Arthritis.</brief_title>
  <official_title>Vitamin D: Does It Help Tregs in Active Rheumatoid Arthritis Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tanta University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tanta University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Regulatory T (Tregs) cells play an important role in the maintenance of immunological&#xD;
      tolerance. It decrease in the peripheral blood of rheumatoid arthritis patients. Vitamin D&#xD;
      has an immunomodulatory and anti-inflammatory effect in rheumatoid arthritis.&#xD;
&#xD;
      Vitamin D supplementation significantly enhances Tregs percentage in the peripheral blood of&#xD;
      RA patients. So supplementation of Vit D improves rheumatoid arthritis disease activity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background: Regulatory T cells (Tregs) play an important role in the maintenance of&#xD;
      immunological tolerance, so Tregs deficiency or decrease suppressor functions may be&#xD;
      associated with development of autoimmune diseases.&#xD;
&#xD;
      Vitamin D is essential for normal bone mineralization and growth, prevention of osteopenia,&#xD;
      osteoporosis, and nonspecific painful musculoskeletal conditions . Vitamin D is thought to&#xD;
      have an immunomodulatory and anti-inflammatory actions, as its receptors are widely expressed&#xD;
      in peripheral mononuclear blood cells, also its deficiency associated with several autoimmune&#xD;
      disorders, including rheumatoid arthritis&#xD;
&#xD;
      Methods: 40 patients with active RA were randomly assigned into two groups. Group I received&#xD;
      MTX plus hydroxychloroquine, group II received MTX and hydroxychloroquine plus vitamin D&#xD;
      supplementation for 3 months, in addition to 30 healthy volunteers as control group.&#xD;
      Peripheral blood Tregs were measured by Flow Cytometry.&#xD;
&#xD;
      Statistical Analysis. The collected data analyzed by SPSS software (version 16). The range,&#xD;
      mean and standard deviation were calculated for quantitative variables. Categorical variables&#xD;
      were expressed as number and percentages; Chi square was used as a test of their&#xD;
      significance. Skewness, kurtosis; Shapiro-Wilk, and The Kolmogorov-Smirnov tests were used to&#xD;
      test the normality for the data. The difference between two means was analyzed using the&#xD;
      students (t) test (paired and unpaired samples- T tests). Significance was considered at&#xD;
      p&lt;0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 6, 2019</start_date>
  <completion_date type="Actual">March 22, 2020</completion_date>
  <primary_completion_date type="Actual">December 22, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>change from base line Measurement of regulatory T cells (CD4+CD25+FoxP3+) at 3 months</measure>
    <time_frame>base line and after 3 months</time_frame>
    <description>4 ml of heparinized blood from the subjects' peripheral blood was collected. Human peripheral blood natural regulatory T cells (Tregs) were surface stained with Mouse Anti-Human CD4 FITC (Fluorescein) conjugated Monoclonal Antibody and Mouse Anti-Human IL-2 Rα/CD25 APC (allophycocyanin) conjugated Monoclonal Antibody, followed by intracellular staining using Rabbit Anti-Human/ Mouse FoxP3 PE (phycoerythrin) conjugated Antigen Affinity-purified Monoclonal Antibody, cells were fixed and permeabilized with FoxP3 Fixation &amp; Permeabilization Buffer Kit. Cells were gated on lymphocytes.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Active Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>group II</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>50000 IU of Vitamin D2 (Ergocalciferol 1.25 mg tablet) weekly for 3 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ergocalciferol 1.25 mg tablet</intervention_name>
    <description>weekly 50000 IU of Vitamin D2 (Ergocalciferol 1.25 mg tablet) given orally group II</description>
    <arm_group_label>group II</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  disease duration less than 3 years from the time of diagnosis, age more than 18 years,&#xD;
             a diagnosis of RA according to the 2010 ACR/ EULAR Classification criteria for RA&#xD;
             diagnosis , active disease according to DAS-28, for those receiving nonsteroidal&#xD;
             anti-inflammatory drugs and corticosteroids, the dosage had to be stable for at least&#xD;
             2 weeks before screening.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with allergic, and infectious diseases, patients receiving steroids for the&#xD;
             first time within 2 weeks before the study, patients with hypercalcemia,&#xD;
             hypercalciuria, nephrolithiasis, or neoplastic diseases were excluded from the study.&#xD;
             We also excluded patients on any biologic therapy and patients with prior use of&#xD;
             leflunomide, hydroxychloroquine, or sulphasalazine for more than 2 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>33 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Souzan E Gado, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lecturer</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hanaa S EL-banna, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lecturer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Souzan Ezzat Gado</name>
      <address>
        <city>Tanta</city>
        <state>EL-gharbia</state>
        <zip>31111</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Wang Z, Chang C, Lu Q. Epigenetics of CD4+ T cells in autoimmune diseases. Curr Opin Rheumatol. 2017 Jul;29(4):361-368. doi: 10.1097/BOR.0000000000000393.</citation>
    <PMID>28362657</PMID>
  </reference>
  <reference>
    <citation>Lan Q, Fan H, Quesniaux V, Ryffel B, Liu Z, Zheng SG. Induced Foxp3(+) regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases? J Mol Cell Biol. 2012 Feb;4(1):22-8. doi: 10.1093/jmcb/mjr039. Epub 2011 Nov 22.</citation>
    <PMID>22107826</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>July 14, 2020</last_update_submitted>
  <last_update_submitted_qc>July 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 15, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tanta University</investigator_affiliation>
    <investigator_full_name>Souzan Ezzat Gado</investigator_full_name>
    <investigator_title>Lecturer of Rheumatology,physical medicine &amp;Rehabilitation.</investigator_title>
  </responsible_party>
  <keyword>Regulatory T cell</keyword>
  <keyword>Foxp3+</keyword>
  <keyword>vitamin D supplementation</keyword>
  <keyword>Rheumatoid arthritis</keyword>
  <keyword>DMARD</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ergocalciferols</mesh_term>
    <mesh_term>Vitamin D</mesh_term>
  </intervention_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/NCT04472481
org study id: 33846
nct id: NCT04472481
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Regulatory T (Tregs) cells play an important role in the maintenance of immunological
      tolerance. It decrease in the peripheral blood of rheumatoid arthritis patients. Vitamin D
      has an immunomodulatory and anti-inflammatory effect in rheumatoid arthritis.

      Vitamin D supplementation significantly enhances Tregs percentage in the peripheral blood of
      RA patients. So supplementation of Vit D improves rheumatoid arthritis disease activity.
Background: Regulatory T cells (Tregs) play an important role in the maintenance of
      immunological tolerance, so Tregs deficiency or decrease suppressor functions may be
      associated with development of autoimmune diseases.

      Vitamin D is essential for normal bone mineralization and growth, prevention of osteopenia,
      osteoporosis, and nonspecific painful musculoskeletal conditions . Vitamin D is thought to
      have an immunomodulatory and anti-inflammatory actions, as its receptors are widely expressed
      in peripheral mononuclear blood cells, also its deficiency associated with several autoimmune
      disorders, including rheumatoid arthritis

      Methods: 40 patients with active RA were randomly assigned into two groups. Group I received
      MTX plus hydroxychloroquine, group II received MTX and hydroxychloroquine plus vitamin D
      supplementation for 3 months, in addition to 30 healthy volunteers as control group.
      Peripheral blood Tregs were measured by Flow Cytometry.

      Statistical Analysis. The collected data analyzed by SPSS software (version 16). The range,
      mean and standard deviation were calculated for quantitative variables. Categorical variables
      were expressed as number and percentages; Chi square was used as a test of their
      significance. Skewness, kurtosis; Shapiro-Wilk, and The Kolmogorov-Smirnov tests were used to
      test the normality for the data. The difference between two means was analyzed using the
      students (t) test (paired and unpaired samples- T tests). Significance was considered at
      p<0.05.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: change from base line Measurement of regulatory T cells (CD4+CD25+FoxP3+) at 3 months
time frame: base line and after 3 months
description: 4 ml of heparinized blood from the subjects' peripheral blood was collected. Human peripheral blood natural regulatory T cells (Tregs) were surface stained with Mouse Anti-Human CD4 FITC (Fluorescein) conjugated Monoclonal Antibody and Mouse Anti-Human IL-2 Rα/CD25 APC (allophycocyanin) conjugated Monoclonal Antibody, followed by intracellular staining using Rabbit Anti-Human/ Mouse FoxP3 PE (phycoerythrin) conjugated Antigen Affinity-purified Monoclonal Antibody, cells were fixed and permeabilized with FoxP3 Fixation & Permeabilization Buffer Kit. Cells were gated on lymphocytes.
arm group label: group II
arm group type: Other
description: 50000 IU of Vitamin D2 (Ergocalciferol 1.25 mg tablet) weekly for 3 months
intervention type: Drug
intervention name: Ergocalciferol 1.25 mg tablet
description: weekly 50000 IU of Vitamin D2 (Ergocalciferol 1.25 mg tablet) given orally group II
arm group label: group II
criteria: 
gender: All
minimum age: 33 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Souzan E Gado, MD
role: Principal Investigator
affiliation: Lecturer
last name: Hanaa S EL-banna, MD
role: Principal Investigator
affiliation: Lecturer
facility: 
country: Egypt
citation: Wang Z, Chang C, Lu Q. Epigenetics of CD4+ T cells in autoimmune diseases. Curr Opin Rheumatol. 2017 Jul;29(4):361-368. doi: 10.1097/BOR.0000000000000393.
PMID: 28362657
citation: Lan Q, Fan H, Quesniaux V, Ryffel B, Liu Z, Zheng SG. Induced Foxp3(+) regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases? J Mol Cell Biol. 2012 Feb;4(1):22-8. doi: 10.1093/jmcb/mjr039. Epub 2011 Nov 22.
PMID: 22107826
responsible party type: Principal Investigator
investigator affiliation: Tanta University
investigator full name: Souzan Ezzat Gado
investigator title: Lecturer of Rheumatology,physical medicine &Rehabilitation.
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Ergocalciferols
mesh term: Vitamin D
sharing ipd: No