<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/NCT01692808</url>
  </required_header>
  <id_info>
    <org_study_id>JP2012042</org_study_id>
    <nct_id>NCT01692808</nct_id>
  </id_info>
  <brief_title>Bioavailability of Vitamin D in Children and Adolescents With Crohn's Disease</brief_title>
  <official_title>Bioavailability of Vitamin D in Children and Adolescents With Crohn's Disease.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Justine's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Justine's Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if high doses of vitamin D3 administered orally as&#xD;
      adjunct therapy to children with Crohn's disease could improve the outcome of the disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background : Crohn's disease is a chronic inflammatory condition affecting all segments of&#xD;
      the digestive tract from the mouth to the anus. This condition is associated with an&#xD;
      increased risk of relapses throughout the course of the disease. Nearly 25% of patients with&#xD;
      Crohn's disease are in the pediatric age range. Many epidemiological data are in favor of an&#xD;
      increase incidence of pediatric Crohn's disease. Environmental factors could explain this&#xD;
      increased incidence. Among them sunlight exposure and vitamin D deficiency have been&#xD;
      suggested by many authors.&#xD;
&#xD;
      Vitamin D, in addition to its action on bone metabolism, exerts an anti-inflammatory effect&#xD;
      by modulating the innate and acquired immune system. The biological effect of high doses of&#xD;
      vitamin D administered orally have not been extensively studied in children with Crohn's&#xD;
      disease. In these patients, the absorption and bioavailability of vitamin D may be altered in&#xD;
      relation with mucosal lesions.&#xD;
&#xD;
      Objective :&#xD;
&#xD;
      Thus our aim is to investigate the effect of high doses of vitamin D3 administered orally as&#xD;
      an adjunct therapy to children with newly diagnosed pediatric Crohn diseases or children in&#xD;
      remission.&#xD;
&#xD;
      Methods : In this Prospective study 40 children will be enrolled and followed up for a&#xD;
      duration of one month. The administration of vitamin D 3000 IU or 4000 IU per day will be&#xD;
      considered as an adjunct to conventional therapy (steroids or enteral nutrition for patients&#xD;
      at diagnosis or immunosuppressants for patients in remission).&#xD;
&#xD;
      Analysis:&#xD;
&#xD;
        1. Tolerance will be assessed during weekly visits by a brief questionnaire and blood&#xD;
           tests.&#xD;
&#xD;
        2. Efficacy will be assessed by monitoring the change in fecal and blood inflammatory&#xD;
           markers.&#xD;
&#xD;
        3. Change in the immunological status will be assessed by measuring the following&#xD;
           parameters :&#xD;
&#xD;
             -  T lymphocyte count CD3, CD4, CD8, and invariant Natural Killer T cell, Treg.&#xD;
&#xD;
             -  Proliferation and activation of CD4 and CD8 T lymphocytes induced by anti-CD3&#xD;
                antibody activator (OKT3). The activation will be evaluated by dosing CD25 and the&#xD;
                proliferation by the study of cell cycle after 3 days of culture of total blood&#xD;
                culture.&#xD;
&#xD;
             -  The culture supernatants will be collected and frozen for subsequent analysis of&#xD;
                cytokines Th1 and Th2 (IFN, IL2, IL4, IL13) with Affymetrix method that allows&#xD;
                simultaneous determination of multiples cytokines.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 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>Number of participants with adverse events after one month</measure>
    <time_frame>up to 1 month</time_frame>
    <description>Tolerance will be assessed weekly by measuring clinical adverse events in relation with high blood level of 25 hydroxy vitamin D.&#xD;
Biological measures will also be performed including : Circulating level of Calcium, phosphorus, PTH.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Decrease of inflammatory parameters</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Evaluate the change from baseline in effect in blood and fecal inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein, faecal Calprotectin).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological changes</measure>
    <time_frame>Baseline and 1 month</time_frame>
    <description>Evaluate the change from baseline in immunological parameters (lymphocytes CD3, CD4, CD8, Treg and iNKT, proliferation and activation of CD4 and CD8).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bioavailability</measure>
    <time_frame>Baseline, after 24 h and then weekly for one month</time_frame>
    <description>The bioavailability will be assessed by measuring the level of 25 hydroxy vitamin D at baseline then 24 hours after the first administration of vitamin D then weekly up to one month and compare this level to baseline.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Crohn's Disease</condition>
  <arm_group>
    <arm_group_label>Exclusive Enteral Nutrition</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>This group is one of the non interventional group. As enteral nutrition is one of the usual therapy of Crohn disease at diagnosis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EEN + Vitamin D3 3000 UI daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exclusive Enteral Nutrition + Vitamin D3 3000 UI daily for one month This arm will be one of the two experimental arms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Corticosteroïd</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Corticosteroids (1mg/kg/day) associated with usual vitamin and calcium supplementation: vitamin D 800 IU of vitamin D3 + 1000 mg calcium per day) for one month</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Corticosteroids + Vitamin D3 4000 UI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Corticosteroids (1mg/kg/day) associated with vitamin D3 4000 UI daily and calcium 1000 mg daily for one month</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D3 4000 UI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vitamin D3 4000 UI /day . This arm is intended for those children in remission with or without immunosuppressant. Vitamin D will be administered in adjunction to usual therapy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3 3000 UI daily</intervention_name>
    <description>Vitamin D3 will be administered as an adjunct to corticosteroids or enteral nutrition at the doses of 3000 UI daily or 4000 UI daily</description>
    <arm_group_label>EEN + Vitamin D3 3000 UI daily</arm_group_label>
    <other_name>Cholecalciferol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin D3 4000 UI daily</intervention_name>
    <description>This arm is intended for those at diagnosis treated with Corticosteroid or in Remission</description>
    <arm_group_label>Corticosteroids + Vitamin D3 4000 UI</arm_group_label>
    <arm_group_label>Vitamin D3 4000 UI</arm_group_label>
    <other_name>Cholecalciferol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age between 10 and 18 years&#xD;
&#xD;
          -  Crohn's disease diagnosed by usual clinical and endoscopic criteria&#xD;
&#xD;
          -  Recent (less than one week) blood test with results of : Albumin, sedimentation rate,&#xD;
             hematocrit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known renal or cardiac malformation&#xD;
&#xD;
          -  Disorders of phospho-calcic metabolism and vitamin D&#xD;
&#xD;
          -  Intake of vitamin D supplementation in the last three months prior to enrollment&#xD;
&#xD;
          -  Current intake of medications known to interfere with the metabolism of calcium,&#xD;
             phosphate and vitamin D *&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Prevost Jantchou, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>mother-child university hospital Ste. Justine Montreal-Canada</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mother-child university hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Jantchou P, Clavel-Chapelon F, Racine A, Kvaskoff M, Carbonnel F, Boutron-Ruault MC. High residential sun exposure is associated with a low risk of incident Crohn's disease in the prospective E3N cohort. Inflamm Bowel Dis. 2014 Jan;20(1):75-81. doi: 10.1097/01.MIB.0000436275.12131.4f.</citation>
    <PMID>24247650</PMID>
  </reference>
  <results_reference>
    <citation>Nerich V, Jantchou P, Boutron-Ruault MC, Monnet E, Weill A, Vanbockstael V, Auleley GR, Balaire C, Dubost P, Rican S, Allemand H, Carbonnel F. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther. 2011 Apr;33(8):940-5. doi: 10.1111/j.1365-2036.2011.04601.x. Epub 2011 Feb 20.</citation>
    <PMID>21332762</PMID>
  </results_reference>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>November 2, 2015</last_update_submitted>
  <last_update_submitted_qc>November 2, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 3, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Justine's Hospital</investigator_affiliation>
    <investigator_full_name>Jantchou Prevost</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Crohn</keyword>
  <keyword>vitamin D</keyword>
  <keyword>remission</keyword>
  <keyword>inflammation</keyword>
  <keyword>tolerance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crohn Disease</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>
  <!-- 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/NCT01692808
org study id: JP2012042
nct id: NCT01692808
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine if high doses of vitamin D3 administered orally as
      adjunct therapy to children with Crohn's disease could improve the outcome of the disease.
Background : Crohn's disease is a chronic inflammatory condition affecting all segments of
      the digestive tract from the mouth to the anus. This condition is associated with an
      increased risk of relapses throughout the course of the disease. Nearly 25% of patients with
      Crohn's disease are in the pediatric age range. Many epidemiological data are in favor of an
      increase incidence of pediatric Crohn's disease. Environmental factors could explain this
      increased incidence. Among them sunlight exposure and vitamin D deficiency have been
      suggested by many authors.

      Vitamin D, in addition to its action on bone metabolism, exerts an anti-inflammatory effect
      by modulating the innate and acquired immune system. The biological effect of high doses of
      vitamin D administered orally have not been extensively studied in children with Crohn's
      disease. In these patients, the absorption and bioavailability of vitamin D may be altered in
      relation with mucosal lesions.

      Objective :

      Thus our aim is to investigate the effect of high doses of vitamin D3 administered orally as
      an adjunct therapy to children with newly diagnosed pediatric Crohn diseases or children in
      remission.

      Methods : In this Prospective study 40 children will be enrolled and followed up for a
      duration of one month. The administration of vitamin D 3000 IU or 4000 IU per day will be
      considered as an adjunct to conventional therapy (steroids or enteral nutrition for patients
      at diagnosis or immunosuppressants for patients in remission).

      Analysis:

        1. Tolerance will be assessed during weekly visits by a brief questionnaire and blood
           tests.

        2. Efficacy will be assessed by monitoring the change in fecal and blood inflammatory
           markers.

        3. Change in the immunological status will be assessed by measuring the following
           parameters :

             -  T lymphocyte count CD3, CD4, CD8, and invariant Natural Killer T cell, Treg.

             -  Proliferation and activation of CD4 and CD8 T lymphocytes induced by anti-CD3
                antibody activator (OKT3). The activation will be evaluated by dosing CD25 and the
                proliferation by the study of cell cycle after 3 days of culture of total blood
                culture.

             -  The culture supernatants will be collected and frozen for subsequent analysis of
                cytokines Th1 and Th2 (IFN, IL2, IL4, IL13) with Affymetrix method that allows
                simultaneous determination of multiples cytokines.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events after one month
time frame: up to 1 month
description: Tolerance will be assessed weekly by measuring clinical adverse events in relation with high blood level of 25 hydroxy vitamin D.
Biological measures will also be performed including : Circulating level of Calcium, phosphorus, PTH.
measure: Decrease of inflammatory parameters
time frame: Baseline and 1 month
description: Evaluate the change from baseline in effect in blood and fecal inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein, faecal Calprotectin).
measure: Immunological changes
time frame: Baseline and 1 month
description: Evaluate the change from baseline in immunological parameters (lymphocytes CD3, CD4, CD8, Treg and iNKT, proliferation and activation of CD4 and CD8).
measure: Bioavailability
time frame: Baseline, after 24 h and then weekly for one month
description: The bioavailability will be assessed by measuring the level of 25 hydroxy vitamin D at baseline then 24 hours after the first administration of vitamin D then weekly up to one month and compare this level to baseline.
arm group label: Exclusive Enteral Nutrition
arm group type: No Intervention
description: This group is one of the non interventional group. As enteral nutrition is one of the usual therapy of Crohn disease at diagnosis.
arm group label: EEN + Vitamin D3 3000 UI daily
arm group type: Experimental
description: Exclusive Enteral Nutrition + Vitamin D3 3000 UI daily for one month This arm will be one of the two experimental arms.
arm group label: Corticosteroïd
arm group type: No Intervention
description: Corticosteroids (1mg/kg/day) associated with usual vitamin and calcium supplementation: vitamin D 800 IU of vitamin D3 + 1000 mg calcium per day) for one month
arm group label: Corticosteroids + Vitamin D3 4000 UI
arm group type: Experimental
description: Corticosteroids (1mg/kg/day) associated with vitamin D3 4000 UI daily and calcium 1000 mg daily for one month
arm group label: Vitamin D3 4000 UI
arm group type: Experimental
description: Vitamin D3 4000 UI /day . This arm is intended for those children in remission with or without immunosuppressant. Vitamin D will be administered in adjunction to usual therapy.
intervention type: Drug
intervention name: Vitamin D3 3000 UI daily
description: Vitamin D3 will be administered as an adjunct to corticosteroids or enteral nutrition at the doses of 3000 UI daily or 4000 UI daily
arm group label: EEN + Vitamin D3 3000 UI daily
other name: Cholecalciferol
intervention type: Drug
intervention name: Vitamin D3 4000 UI daily
description: This arm is intended for those at diagnosis treated with Corticosteroid or in Remission
arm group label: Corticosteroids + Vitamin D3 4000 UI
arm group label: Vitamin D3 4000 UI
other name: Cholecalciferol
criteria: 
gender: All
minimum age: 10 Years
maximum age: 18 Years
healthy volunteers: No
last name: Prevost Jantchou, MD, PHD
role: Principal Investigator
affiliation: mother-child university hospital Ste. Justine Montreal-Canada
facility: 
country: Canada
citation: Jantchou P, Clavel-Chapelon F, Racine A, Kvaskoff M, Carbonnel F, Boutron-Ruault MC. High residential sun exposure is associated with a low risk of incident Crohn's disease in the prospective E3N cohort. Inflamm Bowel Dis. 2014 Jan;20(1):75-81. doi: 10.1097/01.MIB.0000436275.12131.4f.
PMID: 24247650
citation: Nerich V, Jantchou P, Boutron-Ruault MC, Monnet E, Weill A, Vanbockstael V, Auleley GR, Balaire C, Dubost P, Rican S, Allemand H, Carbonnel F. Low exposure to sunlight is a risk factor for Crohn's disease. Aliment Pharmacol Ther. 2011 Apr;33(8):940-5. doi: 10.1111/j.1365-2036.2011.04601.x. Epub 2011 Feb 20.
PMID: 21332762
responsible party type: Principal Investigator
investigator affiliation: St. Justine's Hospital
investigator full name: Jantchou Prevost
investigator title: Professor
mesh term: Crohn Disease
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins