<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/NCT01709474</url>
  </required_header>
  <id_info>
    <org_study_id>DAIT ALE05</org_study_id>
    <nct_id>NCT01709474</nct_id>
  </id_info>
  <brief_title>Vitamin D3 Treatment in Pediatric Systemic Lupus Erythematosus</brief_title>
  <official_title>Vitamin D3 Effects on Immune Function in Pediatric Systemic Lupus Erythematosus (SLE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Autoimmunity Centers of Excellence</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to evaluate the effects of 18 weeks of high-dose&#xD;
      vitamin D3 supplementation compared with standard-dose vitamin D3 supplementation on immune&#xD;
      function, glucose homeostasis, and bone metabolism in children with systemic lupus&#xD;
      erythematosus (SLE) and serum 25-hydroxyvitamin D [25(OH)D] levels ≤20 ng/mL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multi-center, phase II, 18-week, two arm, unblinded randomized clinical trial.&#xD;
&#xD;
      Seventy-eight pediatric subjects with SLE and 25(OH)D levels ≤ 20 ng/mL will be randomized in&#xD;
      a 1:1 ratio to receive either standard-dose (400 IU/day) or high-dose (6,000 IU/day) vitamin&#xD;
      D3 for 18 weeks based upon weight at baseline. Subjects randomized to the high-dose vitamin&#xD;
      D3 treatment arm will receive 6,000 IU per day from baseline until the subject's vitamin D&#xD;
      levels reach ≥ 40 ng/mL at which point the vitamin D3 dose will be reduced to 4,000 IU per&#xD;
      day. Subjects randomized to the high-dose treatment arm weighing &lt; 40 kg will receive&#xD;
      supplementation five days per week and all other subjects will receive supplementation seven&#xD;
      days a week.&#xD;
&#xD;
      In addition to the baseline, and weeks 6, 12, and 18 visits, subjects randomized to the&#xD;
      high-dose treatment arm will return at Weeks 3 and 9 to assess for symptoms of vitamin D&#xD;
      toxicity. If a subject in the high-dose arm is found to exhibit evidence of vitamin D&#xD;
      toxicity at the week 12 visit, he/she will be asked to return to their clinical research site&#xD;
      for an additional vitamin D toxicity assessment at week 15. Study personnel will record each&#xD;
      subject's interval history, assess adverse events, disease activity, and collect samples for&#xD;
      safety and mechanistic assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to slow enrollment&#xD;
  </why_stopped>
  <start_date>June 2013</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Average IFN Module Expression Level</measure>
    <time_frame>Baseline to Week 18</time_frame>
    <description>No mechanistic analyses were performed due to recruitment feasibility issues.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Subjects by Treatment Arm Experiencing Any Adverse Event (AE) ≥ Grade 3</measure>
    <time_frame>Baseline to 18 Weeks</time_frame>
    <description>Adverse event grading based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Systemic Lupus Erythematosus</condition>
  <arm_group>
    <arm_group_label>Vitamin D3 6000 IU</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6000 IU of vitamin D3 by mouth daily until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose is reduced to 4,000 IU/day. Note: Subjects weighing &lt;40 kilograms (kg) at study entry will receive their dose five days a week and all other subjects seven days a week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D3 400 IU</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>400 IU/day of vitamin D3 by mouth daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3 6000 IU</intervention_name>
    <description>Subjects will receive 6,000 IU of vitamin D3 by mouth daily until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose will be reduced to 4,000 IU/day. Note: Subjects weighing &lt;40 kilograms (kg) at study entry will receive their dose five days a week and all other subjects seven days a week.</description>
    <arm_group_label>Vitamin D3 6000 IU</arm_group_label>
    <other_name>high-dose vitamin D</other_name>
    <other_name>high-dose cholecalciferol (D3)</other_name>
    <other_name>high-dose 25(OH)D</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3 400 IU</intervention_name>
    <description>Subjects will receive 400 IU/day of vitamin D3 daily by mouth.</description>
    <arm_group_label>Vitamin D3 400 IU</arm_group_label>
    <other_name>standard-dose vitamin D</other_name>
    <other_name>standard-dose cholecalciferol (D3)</other_name>
    <other_name>standard-dose 25(OH)D</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent signed by the subject or parent/guardian as appropriate;&#xD;
             child assent as appropriate;&#xD;
&#xD;
          -  Before the age of 19, met at least 4 of the 11 modified American College of&#xD;
             Rheumatology (ACR) 1982 Revised Criteria for the Classification of Systemic Lupus&#xD;
             Erythematosus as updated in 1997;&#xD;
&#xD;
          -  Date of SLE diagnosis (as described in Inclusion Criterion 2) at least 24 weeks prior&#xD;
             to randomization;&#xD;
&#xD;
          -  Serum 25-hydroxyvitamin D [25(OH)D] &lt; 20 ng/mL at Screening;&#xD;
&#xD;
          -  SELENA SLEDAI score &gt; 0 and &lt; 8 at Screening and at Baseline;&#xD;
&#xD;
          -  If taking prednisone (or equivalent corticosteroid), the dose must be ≤ 15 mg/day or&#xD;
             ≤0.5 mg/kg/day, whichever is lower, and stable for at least four weeks prior to&#xD;
             randomization. Note, if subjects are taking steroids every other day, divide their&#xD;
             dose by 2 to evaluate eligibility;&#xD;
&#xD;
          -  Stable immunosuppressive dose for at least 12 weeks prior to randomization;&#xD;
&#xD;
             --Immunosuppressive medications allowed include mycophenolate (MMF), azathioprine,&#xD;
             methotrexate, antimalarial medications (e.g., hydroxychloroquine), cyclosporine A&#xD;
             (CsA), tacrolimus, intravenous immune globulin (IVIG), and abatacept.&#xD;
&#xD;
          -  Body weight &gt; 25 kg;&#xD;
&#xD;
          -  Able to swallow pills;&#xD;
&#xD;
          -  Males and females with reproductive potential must agree to practice effective&#xD;
             measures of birth control.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any condition or treatment that, in the opinion of the investigator, places the&#xD;
             subject at an unacceptable risk as a participant in the trial;&#xD;
&#xD;
          -  Current pharmacologic vitamin D2 or D3 intake &gt; 800 IU daily or use of calcitriol at&#xD;
             any dose over the past four weeks prior to randomization;&#xD;
&#xD;
          -  Cyclophosphamide or IV glucocorticoid exposure within 12 weeks prior to randomization;&#xD;
&#xD;
          -  Any BILAG A or B manifestation with the exception of a BILAG B mucocutaneous&#xD;
             manifestation at screening, and excluding the renal BILAG criteria (see rituximab or&#xD;
             belimumab criterion, below);&#xD;
&#xD;
          -  Significant renal insufficiency defined as:&#xD;
&#xD;
               -  Estimated GFR &lt; 60 mL/min/1.73m^2 or estimated GFR &lt; 90 mL/min/1.73m^2 with a&#xD;
                  reduction of the GFR by &gt; 15% from the last measurement;&#xD;
&#xD;
               -  Urine dipstick value of 2+ or higher for protein, unless this is a stable value&#xD;
                  from the last measurement or, urine protein-creatinine ratio ≥ 50 mg/mmol unless&#xD;
                  the value represents an improvement of ≥ 25% from the last measurement.&#xD;
&#xD;
          -  Rituximab or belimumab exposure use within 24 weeks prior to randomization;&#xD;
&#xD;
          -  The following laboratory parameters at the Screening visit:&#xD;
&#xD;
               -  Platelets &lt; 50,000; WBC &lt; 2,500; ANC &lt; 1,000;&#xD;
&#xD;
               -  Hemoglobin &lt; 9 mg/dL;&#xD;
&#xD;
               -  ALT, AST, bilirubin &gt; 2x upper limit of normal (ULN);&#xD;
&#xD;
               -  Hypercalcemia (calcium &gt; ULN);&#xD;
&#xD;
               -  Hypercalciuria (urinary calcium/creatinine ratio &gt; 0.2).&#xD;
&#xD;
          -  Primary hyperparathyroidism (known);&#xD;
&#xD;
          -  History of nephrolithiasis (known);&#xD;
&#xD;
          -  Diabetes mellitus requiring insulin therapy;&#xD;
&#xD;
          -  Medications that interfere with vitamin D absorption;&#xD;
&#xD;
          -  History of vertebral compression fractures (known);&#xD;
&#xD;
          -  Pregnancy (girls ≥ 11 years of age must have a negative urine/serum pregnancy test);&#xD;
&#xD;
          -  A history of non-adherence/non-compliance;&#xD;
&#xD;
          -  Other investigational drug and/or treatment during the four weeks or seven half-lives&#xD;
             of the other investigational drug prior to the start of study product dosing (Day 0),&#xD;
             whichever is the greater length of time to enrollment;&#xD;
&#xD;
          -  Current diagnosis of cancer or chronic infection such as Hepatitis B, Hepatitis C, or&#xD;
             tuberculosis;&#xD;
&#xD;
          -  Treatment with digoxin;&#xD;
&#xD;
          -  Flu (influenza) vaccination within one week prior to randomization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>20 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jon M Burnham, MD, MSCE</last_name>
    <role>Study Chair</role>
    <affiliation>University of Pennsylvania</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emily Von Scheven, MD, MAS</last_name>
    <role>Study Chair</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lucile Packard Children's Hospital, Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF School of Medicine</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ann &amp; Robert H. Lurie Children's Hospital of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riley Hospital for Children</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Medical Center of Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's Hospital</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.niaid.nih.gov</url>
    <description>National Institute of Allergy and Infectious Diseases (NIAID)</description>
  </link>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>October 20, 2015</results_first_submitted>
  <results_first_submitted_qc>November 27, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">December 3, 2015</results_first_posted>
  <last_update_submitted>December 15, 2015</last_update_submitted>
  <last_update_submitted_qc>December 15, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 17, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SLE</keyword>
  <keyword>Vitamin D3</keyword>
  <keyword>Vitamin D deficiency</keyword>
  <keyword>IFN alpha expression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</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>Ergocalciferols</mesh_term>
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Vitamins</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Vitamin D3 6000 IU</title>
          <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 6,000 international units [IU] daily).</description>
        </group>
        <group group_id="P2">
          <title>Vitamin D3 400 IU</title>
          <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 400 international units [IU] daily).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The population included all subjects who were randomized to receive either Vitamin D3 6000 IU daily or 400 IU daily.</population>
      <group_list>
        <group group_id="B1">
          <title>Vitamin D3 6000 IU</title>
          <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 6,000 international units [IU] daily).</description>
        </group>
        <group group_id="B2">
          <title>Vitamin D3 400 IU</title>
          <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 400 international units [IU] daily).</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="3"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="7"/>
          </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="16.3" spread="3.8"/>
                    <measurement group_id="B2" value="13.5" spread="0.6"/>
                    <measurement group_id="B3" value="14.7" spread="2.7"/>
                  </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="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </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>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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </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="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>25(OH)D at Screening</title>
          <description>25(OH)D is also called vitamin D3. Participants were required to have a screening value of less than 20 ng/mL to be eligible for the study.</description>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.3" spread="3.9"/>
                    <measurement group_id="B2" value="16.1" spread="2.5"/>
                    <measurement group_id="B3" value="13.2" spread="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Average IFN Module Expression Level</title>
        <description>No mechanistic analyses were performed due to recruitment feasibility issues.</description>
        <time_frame>Baseline to Week 18</time_frame>
        <population>Data were not collected and therefore no analyses could be performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Vitamin D3 6000 IU</title>
            <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 6,000 international units [IU] daily).</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3 400 IU</title>
            <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 400 international units [IU] daily).</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Average IFN Module Expression Level</title>
          <description>No mechanistic analyses were performed due to recruitment feasibility issues.</description>
          <population>Data were not collected and therefore no analyses could be performed.</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>Primary</type>
        <title>Percentage of Subjects by Treatment Arm Experiencing Any Adverse Event (AE) ≥ Grade 3</title>
        <description>Adverse event grading based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0</description>
        <time_frame>Baseline to 18 Weeks</time_frame>
        <population>Intent-to-treat</population>
        <group_list>
          <group group_id="O1">
            <title>Vitamin D3 6000 IU</title>
            <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 6,000 international units [IU] daily).</description>
          </group>
          <group group_id="O2">
            <title>Vitamin D3 400 IU</title>
            <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 400 international units [IU] daily).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects by Treatment Arm Experiencing Any Adverse Event (AE) ≥ Grade 3</title>
          <description>Adverse event grading based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0</description>
          <population>Intent-to-treat</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of administration of the first dose of study drug until the participant completed study participation, an average of 18 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vitamin D3 6000 IU</title>
          <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 6,000 international units [IU] daily).</description>
        </group>
        <group group_id="E2">
          <title>Vitamin D3 400 IU</title>
          <description>Participants received an 18-week course of oral Vitamin D3 (cholecalciferol, 400 international units [IU] daily).</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="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalciuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </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 study terminated early due to recruitment feasibility issues. Seven subjects were enrolled and received treatment in contrast to the planned number of 78 subjects for randomization/receipt of treatment. No mechanistic analyses were performed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Director, Clinical Research Operations Program</name_or_title>
      <organization>DAIT/NIAID</organization>
      <phone>301-594-7669</phone>
      <email>DAITClinicalTrialsGov@niaid.nih.gov</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/NCT01709474
org study id: DAIT ALE05
nct id: NCT01709474
lead sponsor: 
collaborator: 
has dmc: Yes
The primary objective of this study is to evaluate the effects of 18 weeks of high-dose
      vitamin D3 supplementation compared with standard-dose vitamin D3 supplementation on immune
      function, glucose homeostasis, and bone metabolism in children with systemic lupus
      erythematosus (SLE) and serum 25-hydroxyvitamin D [25(OH)D] levels ≤20 ng/mL.
This is a multi-center, phase II, 18-week, two arm, unblinded randomized clinical trial.

      Seventy-eight pediatric subjects with SLE and 25(OH)D levels ≤ 20 ng/mL will be randomized in
      a 1:1 ratio to receive either standard-dose (400 IU/day) or high-dose (6,000 IU/day) vitamin
      D3 for 18 weeks based upon weight at baseline. Subjects randomized to the high-dose vitamin
      D3 treatment arm will receive 6,000 IU per day from baseline until the subject's vitamin D
      levels reach ≥ 40 ng/mL at which point the vitamin D3 dose will be reduced to 4,000 IU per
      day. Subjects randomized to the high-dose treatment arm weighing < 40 kg will receive
      supplementation five days per week and all other subjects will receive supplementation seven
      days a week.

      In addition to the baseline, and weeks 6, 12, and 18 visits, subjects randomized to the
      high-dose treatment arm will return at Weeks 3 and 9 to assess for symptoms of vitamin D
      toxicity. If a subject in the high-dose arm is found to exhibit evidence of vitamin D
      toxicity at the week 12 visit, he/she will be asked to return to their clinical research site
      for an additional vitamin D toxicity assessment at week 15. Study personnel will record each
      subject's interval history, assess adverse events, disease activity, and collect samples for
      safety and mechanistic assessments.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Average IFN Module Expression Level
time frame: Baseline to Week 18
description: No mechanistic analyses were performed due to recruitment feasibility issues.
measure: Percentage of Subjects by Treatment Arm Experiencing Any Adverse Event (AE) ≥ Grade 3
time frame: Baseline to 18 Weeks
description: Adverse event grading based on National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0
arm group label: Vitamin D3 6000 IU
arm group type: Experimental
description: 6000 IU of vitamin D3 by mouth daily until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose is reduced to 4,000 IU/day. Note: Subjects weighing <40 kilograms (kg) at study entry will receive their dose five days a week and all other subjects seven days a week.
arm group label: Vitamin D3 400 IU
arm group type: Active Comparator
description: 400 IU/day of vitamin D3 by mouth daily.
intervention type: Drug
intervention name: Vitamin D3 6000 IU
description: Subjects will receive 6,000 IU of vitamin D3 by mouth daily until the subject's serum 25(OH) level is ≥ 40ng/mL at which point the supplementation dose will be reduced to 4,000 IU/day. Note: Subjects weighing <40 kilograms (kg) at study entry will receive their dose five days a week and all other subjects seven days a week.
arm group label: Vitamin D3 6000 IU
other name: high-dose vitamin D
other name: high-dose cholecalciferol (D3)
other name: high-dose 25(OH)D
intervention type: Drug
intervention name: Vitamin D3 400 IU
description: Subjects will receive 400 IU/day of vitamin D3 daily by mouth.
arm group label: Vitamin D3 400 IU
other name: standard-dose vitamin D
other name: standard-dose cholecalciferol (D3)
other name: standard-dose 25(OH)D
criteria: 
gender: All
minimum age: 5 Years
maximum age: 20 Years
healthy volunteers: No
last name: Jon M Burnham, MD, MSCE
role: Study Chair
affiliation: University of Pennsylvania
last name: Emily Von Scheven, MD, MAS
role: Study Chair
affiliation: University of California, San Francisco
facility: 
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facility: 
country: United States
url: http://www.niaid.nih.gov
description: National Institute of Allergy and Infectious Diseases (NIAID)
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study terminated early due to recruitment feasibility issues. Seven subjects were enrolled and received treatment in contrast to the planned number of 78 subjects for randomization/receipt of treatment. No mechanistic analyses were performed.
point of contact: 