<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/NCT01724190</url>
  </required_header>
  <id_info>
    <org_study_id>285412</org_study_id>
    <nct_id>NCT01724190</nct_id>
  </id_info>
  <brief_title>Effect of Vitamin D on the Honeymoon Period in Children and Adolescents With Type 1 Diabetes</brief_title>
  <official_title>Effect of Vitamin D Supplementation on Rate of Partial Clinical Remission in Children and Adolescents With Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nationwide Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nationwide Children's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if supplementation with Vitamin D in children and&#xD;
      adolescents with newly diagnosed type 1 diabetes increases the number of patients who enter&#xD;
      the honeymoon period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Type 1 diabetes is an autoimmune disease characterized by destruction of the insulin&#xD;
      secreting beta-cells of the pancreas. There is evidence that Vitamin D may play a role in the&#xD;
      initial risk of development of autoimmune disease, including type 1 diabetes. However,&#xD;
      Vitamin D may also play a role the natural progression of type 1 diabetes by altering innate&#xD;
      insulin secretion and sensitivity and by influencing systemic inflammation, directly at the&#xD;
      level of the beta-cell. Studies have shown that Vitamin D insufficiency or deficiency is&#xD;
      frequently reported in children and adolescents with type 1 diabetes. A majority of newly&#xD;
      diagnosed patients with type 1 diabetes enter a period of partial clinical remission,&#xD;
      characterized by low or even absent insulin requirements, also known as a honeymoon period.&#xD;
      This honeymoon period is associated with improved metabolic control, near normal insulin&#xD;
      sensitivity, and recovery of beta-cell function leading to preservation of endogenous insulin&#xD;
      secretion. We hypothesize that supplementation with Vitamin D in children and adolescents&#xD;
      with newly diagnosed type 1 diabetes will halt the destructive process within the beta cell&#xD;
      and improve beta-cell function by increasing endogenous insulin secretion and decreasing&#xD;
      systemic inflammation, thereby increasing the rate of partial clinical remission.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>N/A</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>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>IDAA1c</measure>
    <time_frame>9 months disease duration</time_frame>
    <description>Our primary outcome measure will be to determine the rate of partial clinical remission at 9 months of disease duration, which will be assessed by determining insulin dose adjusted hemoglobin A1c (IDAA1c) using the formula (HbA1c% + [4 x insulin dose u/kg/day]). A IDAA1c &lt;9 will be indicative of partial clinical remission.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>fasting c-peptide</measure>
    <time_frame>diagnosis and 9 months disease duration</time_frame>
    <description>Endogenous insulin production and secretion will be determined by measuring changes in fasting c-peptide levels at diagnosis and at 9 months of disease duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>high sensitivity c-reactive protein (hsCRP)</measure>
    <time_frame>diagnosis and 9 months disease duration</time_frame>
    <description>Changes in systemic inflammation will be determined by measuring hsCRP at diagnosis and at 9 months of disease duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>interleukin-6 (IL-6)</measure>
    <time_frame>diagnosis and 9 months disease duration</time_frame>
    <description>Changes in systemic inflammation will be determined by measuring IL-6 at diagnosis and 9 months of disease duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tumor necrosis factor-alpha (TNF-alpha)</measure>
    <time_frame>diagnosis and 9 months disease duration</time_frame>
    <description>Changes in systemic inflammation will be determined by measuring TNF-alpha at diagnosis and 9 months of disease duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>25-(OD)D</measure>
    <time_frame>diagnosis and 9 months disease duration</time_frame>
    <description>Comparisons will be made between 25-(OH)D status at diagnosis and 9 months disease duration with IDAA1c at 3, 6, and 9 months to assess the relationship between 25-(OD)D and our primary outcome of partial clinical remission.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Vitamin D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will receive oral vitamin D supplementation, 3000 IU daily over the course of 9 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will receive a placebo solution daily over the course of 9 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D</intervention_name>
    <arm_group_label>Vitamin D</arm_group_label>
    <other_name>Cholecalciferol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  children and adolescents ages 4-18 years old with newly diagnosed type 1 diabetes.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age less than 4 years&#xD;
&#xD;
          -  pregnant females&#xD;
&#xD;
          -  previous or known history of Vitamin D deficiency or insufficiency&#xD;
&#xD;
          -  current use of Vitamin D supplementation or multi-vitamin containing &gt;800 IU daily&#xD;
&#xD;
          -  or concurrent development and/or history of other significant systemic illness or&#xD;
             non-endocrine autoimmune disorder.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathryn J Stephens, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nationwide Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <last_update_submitted>June 19, 2015</last_update_submitted>
  <last_update_submitted_qc>June 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 22, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
    <investigator_full_name>Kathryn Obrynba</investigator_full_name>
    <investigator_title>Endocrinology Fellow</investigator_title>
  </responsible_party>
  <keyword>Type 1 Diabetes</keyword>
  <keyword>Vitamin D</keyword>
  <keyword>Clinical Remission</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</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>
  <!-- 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/NCT01724190
org study id: 285412
nct id: NCT01724190
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine if supplementation with Vitamin D in children and
      adolescents with newly diagnosed type 1 diabetes increases the number of patients who enter
      the honeymoon period.
Type 1 diabetes is an autoimmune disease characterized by destruction of the insulin
      secreting beta-cells of the pancreas. There is evidence that Vitamin D may play a role in the
      initial risk of development of autoimmune disease, including type 1 diabetes. However,
      Vitamin D may also play a role the natural progression of type 1 diabetes by altering innate
      insulin secretion and sensitivity and by influencing systemic inflammation, directly at the
      level of the beta-cell. Studies have shown that Vitamin D insufficiency or deficiency is
      frequently reported in children and adolescents with type 1 diabetes. A majority of newly
      diagnosed patients with type 1 diabetes enter a period of partial clinical remission,
      characterized by low or even absent insulin requirements, also known as a honeymoon period.
      This honeymoon period is associated with improved metabolic control, near normal insulin
      sensitivity, and recovery of beta-cell function leading to preservation of endogenous insulin
      secretion. We hypothesize that supplementation with Vitamin D in children and adolescents
      with newly diagnosed type 1 diabetes will halt the destructive process within the beta cell
      and improve beta-cell function by increasing endogenous insulin secretion and decreasing
      systemic inflammation, thereby increasing the rate of partial clinical remission.
allocation: Randomized
intervention model: Parallel Assignment
masking: Triple (Participant, Care Provider, Investigator)
measure: IDAA1c
time frame: 9 months disease duration
description: Our primary outcome measure will be to determine the rate of partial clinical remission at 9 months of disease duration, which will be assessed by determining insulin dose adjusted hemoglobin A1c (IDAA1c) using the formula (HbA1c% + [4 x insulin dose u/kg/day]). A IDAA1c <9 will be indicative of partial clinical remission.
measure: fasting c-peptide
time frame: diagnosis and 9 months disease duration
description: Endogenous insulin production and secretion will be determined by measuring changes in fasting c-peptide levels at diagnosis and at 9 months of disease duration.
measure: high sensitivity c-reactive protein (hsCRP)
time frame: diagnosis and 9 months disease duration
description: Changes in systemic inflammation will be determined by measuring hsCRP at diagnosis and at 9 months of disease duration.
measure: interleukin-6 (IL-6)
time frame: diagnosis and 9 months disease duration
description: Changes in systemic inflammation will be determined by measuring IL-6 at diagnosis and 9 months of disease duration.
measure: tumor necrosis factor-alpha (TNF-alpha)
time frame: diagnosis and 9 months disease duration
description: Changes in systemic inflammation will be determined by measuring TNF-alpha at diagnosis and 9 months of disease duration.
measure: 25-(OD)D
time frame: diagnosis and 9 months disease duration
description: Comparisons will be made between 25-(OH)D status at diagnosis and 9 months disease duration with IDAA1c at 3, 6, and 9 months to assess the relationship between 25-(OD)D and our primary outcome of partial clinical remission.
arm group label: Vitamin D
arm group type: Active Comparator
description: Subjects will receive oral vitamin D supplementation, 3000 IU daily over the course of 9 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects will receive a placebo solution daily over the course of 9 months.
intervention type: Drug
intervention name: Vitamin D
arm group label: Vitamin D
other name: Cholecalciferol
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 4 Years
maximum age: 18 Years
healthy volunteers: No
last name: Kathryn J Stephens, MD
role: Principal Investigator
affiliation: Nationwide Children's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Nationwide Children's Hospital
investigator full name: Kathryn Obrynba
investigator title: Endocrinology Fellow
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Vitamin D
mesh term: Cholecalciferol