<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/NCT01667796</url>
  </required_header>
  <id_info>
    <org_study_id>NA_00049428</org_study_id>
    <secondary_id>FG-1507-05231</secondary_id>
    <nct_id>NCT01667796</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics of Vitamin D in Multiple Sclerosis and in Health</brief_title>
  <official_title>Pharmacodynamic and Immunologic Effects of Vitamin D Supplementation in Patients With Multiple Sclerosis and Healthy Controls</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Multiple Sclerosis Society</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study of oral vitamin D supplementation to determine if patients with&#xD;
      Multiple Sclerosis (MS) and healthy individuals attain a similar increase in serum&#xD;
      25-hydroxyvitamin D levels. The investigators will also assess whether the immunologic or&#xD;
      relevant gene expression response to oral vitamin D supplementation differs in patients with&#xD;
      MS and healthy controls.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2010</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mean Serum Level of 25-hydroxyvitamin D</measure>
    <time_frame>Baseline to 90 days</time_frame>
    <description>Generalized estimating equations (GEE) with an autoregressive with lag one correlation matrix were used to compare the serially-measured serum 25(OH)D levels between MS patients and Healthy Controls (HCs) to take into account repeated measures and within-subject correlations.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+)</measure>
    <time_frame>Baseline, 90 days</time_frame>
    <description>Analyzed the mean percentage change in IFNγ+ and IL-17+ cluster of differentiation 4 (CD4) + cells (post- versus pre- supplementation). This represents a change between two time points (90 days versus baseline).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gene Expression Microarray</measure>
    <time_frame>90 days</time_frame>
    <description>We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cytokine Levels</measure>
    <time_frame>90 days</time_frame>
    <description>The original plan had been to measure the change in basic serum cytokine levels (e.g. IL-17, interferon gamma; IL-10; pg/microliter). However, due to emerging data suggesting low utility of these measures, this plan was abandoned.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Percentage of B Cells</measure>
    <time_frame>90 days</time_frame>
    <description>The change in percentage (day 90-baseline) was originally planned for study. Due to the limited number of patients with samples this plan was abandoned.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Multiple Sclerosis, Relapsing-remitting</condition>
  <arm_group>
    <arm_group_label>Vitamin D3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Both those with MS and healthy controls will be given vitamin D3 5000 IU/day by mouth for 90 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D3</intervention_name>
    <arm_group_label>Vitamin D3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Healthy or multiple sclerosis&#xD;
&#xD;
          -  Aged 18 to 60&#xD;
&#xD;
          -  Body mass index is between 18 kg/m2 and 30 kg/m2&#xD;
&#xD;
          -  Screening 25-hydroxyvitamin D level ≤ 75 nmol/L (30 ng/mL)&#xD;
&#xD;
          -  White race&#xD;
&#xD;
          -  Non-Hispanic ethnicity&#xD;
&#xD;
          -  Willing to use birth control during study&#xD;
&#xD;
          -  Willing to not use tanning bed during study&#xD;
&#xD;
        If subject has multiple sclerosis:&#xD;
&#xD;
          -  Relapsing-remitting MS, as defined by McDonald 2005 criteria&#xD;
&#xD;
          -  Screening Expanded Disability Status Scale score ≤ 3.0&#xD;
&#xD;
          -  Using no medication for MS, or taking Copaxone, (glatiramer acetate), interferons, or&#xD;
             natalizumab&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or nursing&#xD;
&#xD;
          -  Taking multivitamin &amp; unwilling to remain off it during study&#xD;
&#xD;
          -  Taking cod liver oil &amp; unwilling to remain off it during study&#xD;
&#xD;
          -  On a fat-restricted diet&#xD;
&#xD;
          -  History of renal disease or nephrolithiasis (kidney stones)&#xD;
&#xD;
          -  History of liver disease&#xD;
&#xD;
          -  Taking thiazide diuretics&#xD;
&#xD;
          -  History of hyperthyroidism&#xD;
&#xD;
          -  History of infection with Mycobacterium species&#xD;
&#xD;
          -  History of sarcoidosis&#xD;
&#xD;
          -  History of cancer&#xD;
&#xD;
          -  History of cardiac disease&#xD;
&#xD;
          -  History of HIV&#xD;
&#xD;
          -  History of gastrointestinal disorder&#xD;
&#xD;
          -  Taking medications that interfere with gastrointestinal absorption&#xD;
&#xD;
          -  Cigarette smoker in past month&#xD;
&#xD;
          -  Use of illicit drugs in past month&#xD;
&#xD;
          -  Use of steroids in past month&#xD;
&#xD;
          -  History of hypercalcemia, and screening serum calcium ≤ 10 mg/dL (UCSF) or ≤ 10.7&#xD;
             mg/dL (Johns Hopkins)&#xD;
&#xD;
          -  History of hypercalciuria&#xD;
&#xD;
          -  Evidence of anemia (Hgb &lt;11.0 g/dL)&#xD;
&#xD;
          -  History of other serious medical conditions&#xD;
&#xD;
          -  Taking medications that involve the P450 system or may interact with vitamin D&#xD;
             (digoxin, diltiazem, verapamil, cimetidine, heparin, or low-molecular weight heparin)&#xD;
&#xD;
          -  Other concerns about safety from the perspective of the treating physician&#xD;
&#xD;
        If subject has MS:&#xD;
&#xD;
        -History of major heat sensitivity (leading to sun-avoidant behaviors)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ellen M Mowry, MD, MCR</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>August 25, 2015</results_first_submitted>
  <results_first_submitted_qc>December 29, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 1, 2016</results_first_posted>
  <last_update_submitted>March 1, 2019</last_update_submitted>
  <last_update_submitted_qc>March 1, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 5, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple sclerosis</keyword>
  <keyword>Healthy controls</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Vitamin D</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Multiple Sclerosis (MS) Subjects</title>
          <description>MS patients</description>
        </group>
        <group group_id="P2">
          <title>Healthy Controls</title>
          <description>Healthy control subjects</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>MS Subjects</title>
          <description>Female subjects with MS</description>
        </group>
        <group group_id="B2">
          <title>Healthy Controls</title>
          <description>Female subjects without MS</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="27"/>
            <count group_id="B2" value="30"/>
            <count group_id="B3" value="57"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.2" spread="9.2"/>
                    <measurement group_id="B2" value="37.9" spread="12.1"/>
                    <measurement group_id="B3" value="38.9" spread="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Mean Serum Level of 25-hydroxyvitamin D</title>
        <description>Generalized estimating equations (GEE) with an autoregressive with lag one correlation matrix were used to compare the serially-measured serum 25(OH)D levels between MS patients and Healthy Controls (HCs) to take into account repeated measures and within-subject correlations.</description>
        <time_frame>Baseline to 90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MS Subjects</title>
            <description>Female subjects with MS</description>
          </group>
          <group group_id="O2">
            <title>Healthy Controls</title>
            <description>Female subjects without MS</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mean Serum Level of 25-hydroxyvitamin D</title>
          <description>Generalized estimating equations (GEE) with an autoregressive with lag one correlation matrix were used to compare the serially-measured serum 25(OH)D levels between MS patients and Healthy Controls (HCs) to take into account repeated measures and within-subject correlations.</description>
          <units>nmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.9" spread="5.9"/>
                    <measurement group_id="O2" value="82.4" spread="5.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.001</p_value>
            <method>univariate generalized estimating equati</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.008</p_value>
            <p_value_desc>Adjusted for adherence, body mass index, and oral contraceptive use</p_value_desc>
            <method>Generalized estimating equation</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+)</title>
        <description>Analyzed the mean percentage change in IFNγ+ and IL-17+ cluster of differentiation 4 (CD4) + cells (post- versus pre- supplementation). This represents a change between two time points (90 days versus baseline).</description>
        <time_frame>Baseline, 90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>MS Subjects</title>
            <description>MS patients</description>
          </group>
          <group group_id="O2">
            <title>Healthy Controls</title>
            <description>Healthy control subjects</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+)</title>
          <description>Analyzed the mean percentage change in IFNγ+ and IL-17+ cluster of differentiation 4 (CD4) + cells (post- versus pre- supplementation). This represents a change between two time points (90 days versus baseline).</description>
          <units>percentage of cells</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>mean percentage change in IFNγ+ CD4+ cells</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.2" spread="4.2"/>
                    <measurement group_id="O2" value="-13.2" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mean percentage change in IL-17+ CD4+ cells</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.21" spread="0.77"/>
                    <measurement group_id="O2" value="-0.17" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gene Expression Microarray</title>
        <description>We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.</description>
        <time_frame>90 days</time_frame>
        <population>We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>Gene Expression: MS vs HC</title>
            <description>Gene expression analyses have been cancelled as a secondary outcome as laboratory techniques developed since the original study was started indicated that whole blood gene expression is unlikely to be informative.</description>
          </group>
        </group_list>
        <measure>
          <title>Gene Expression Microarray</title>
          <description>We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.</description>
          <population>We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Cytokine Levels</title>
        <description>The original plan had been to measure the change in basic serum cytokine levels (e.g. IL-17, interferon gamma; IL-10; pg/microliter). However, due to emerging data suggesting low utility of these measures, this plan was abandoned.</description>
        <time_frame>90 days</time_frame>
        <population>Cytokine levels data were not analyzed and are no longer planned to be measured as outcomes.</population>
        <group_list>
          <group group_id="O1">
            <title>Multiple Sclerosis (MS) Subjects</title>
            <description>MS patients</description>
          </group>
          <group group_id="O2">
            <title>Healthy Controls</title>
            <description>Healthy control subjects</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Cytokine Levels</title>
          <description>The original plan had been to measure the change in basic serum cytokine levels (e.g. IL-17, interferon gamma; IL-10; pg/microliter). However, due to emerging data suggesting low utility of these measures, this plan was abandoned.</description>
          <population>Cytokine levels data were not analyzed and are no longer planned to be measured as outcomes.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Percentage of B Cells</title>
        <description>The change in percentage (day 90-baseline) was originally planned for study. Due to the limited number of patients with samples this plan was abandoned.</description>
        <time_frame>90 days</time_frame>
        <population>B Cell data were not analyzed and are no longer planned to be measured as outcomes.</population>
        <group_list>
          <group group_id="O1">
            <title>Multiple Sclerosis (MS) Subjects</title>
            <description>MS patients</description>
          </group>
          <group group_id="O2">
            <title>Healthy Controls</title>
            <description>Healthy control subjects</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Percentage of B Cells</title>
          <description>The change in percentage (day 90-baseline) was originally planned for study. Due to the limited number of patients with samples this plan was abandoned.</description>
          <population>B Cell data were not analyzed and are no longer planned to be measured as outcomes.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>MS Subjects</title>
          <description>MS patients</description>
        </group>
        <group group_id="E2">
          <title>Healthy Controls</title>
          <description>Healthy control subjects</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <description>A control got palpitations. Cardiac workup: rare premature atrial and ventricular contractions; the person then reported remote atrial fibrillation (not disclosed at screening visit). This was not deemed to be related to vitamin D supplementation.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The generalizability of the findings of this study (beyond female Caucasians) has to be further tested. It is possible that there were unmeasured confounders influencing results.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Ellen Mowry</name_or_title>
      <organization>Johns Hopkins</organization>
      <phone>4106141522</phone>
      <email>vitamindtrialms@jhmi.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01667796
org study id: NA_00049428
secondary id: FG-1507-05231
nct id: NCT01667796
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This is a pilot study of oral vitamin D supplementation to determine if patients with
      Multiple Sclerosis (MS) and healthy individuals attain a similar increase in serum
      25-hydroxyvitamin D levels. The investigators will also assess whether the immunologic or
      relevant gene expression response to oral vitamin D supplementation differs in patients with
      MS and healthy controls.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Change in Mean Serum Level of 25-hydroxyvitamin D
time frame: Baseline to 90 days
description: Generalized estimating equations (GEE) with an autoregressive with lag one correlation matrix were used to compare the serially-measured serum 25(OH)D levels between MS patients and Healthy Controls (HCs) to take into account repeated measures and within-subject correlations.
measure: Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+)
time frame: Baseline, 90 days
description: Analyzed the mean percentage change in IFNγ+ and IL-17+ cluster of differentiation 4 (CD4) + cells (post- versus pre- supplementation). This represents a change between two time points (90 days versus baseline).
measure: Gene Expression Microarray
time frame: 90 days
description: We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted.
measure: Change in Cytokine Levels
time frame: 90 days
description: The original plan had been to measure the change in basic serum cytokine levels (e.g. IL-17, interferon gamma; IL-10; pg/microliter). However, due to emerging data suggesting low utility of these measures, this plan was abandoned.
measure: Change in Percentage of B Cells
time frame: 90 days
description: The change in percentage (day 90-baseline) was originally planned for study. Due to the limited number of patients with samples this plan was abandoned.
arm group label: Vitamin D3
arm group type: Experimental
description: Both those with MS and healthy controls will be given vitamin D3 5000 IU/day by mouth for 90 days.
intervention type: Dietary Supplement
intervention name: Vitamin D3
arm group label: Vitamin D3
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ellen M Mowry, MD, MCR
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Sclerosis
mesh term: Vitamin D
mesh term: Cholecalciferol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The generalizability of the findings of this study (beyond female Caucasians) has to be further tested. It is possible that there were unmeasured confounders influencing results.
point of contact: 