<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/NCT02238418</url>
  </required_header>
  <id_info>
    <org_study_id>2013-812</org_study_id>
    <secondary_id>2013-002710-13</secondary_id>
    <nct_id>NCT02238418</nct_id>
  </id_info>
  <brief_title>Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.</brief_title>
  <acronym>VITATOL</acronym>
  <official_title>Vitamin D Supplementation in Children and Adolescents Seen in the Paediatric Nephrology Service: Study of the Efficacy of Service Usual Care (Cholecalciferol) and Its Impact on Calciuria.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vitamin D is not seen anymore only as a phosphocalcic and bone hormone, but also as having an&#xD;
      effect on global health (anti-infective, anti-inflammatory, anti-tumour roles and&#xD;
      cardiovascular protection).&#xD;
&#xD;
      Until recently, vitamin D repletion was defined as the minimal concentration that enables the&#xD;
      prevention of rickets in children and osteomalacia in adults, i.e, approximately 8 ng/mL (20&#xD;
      nmol/L). However, most of the international experts agree to set minimal threshold of 25 OH&#xD;
      vitamin D serum concentration, higher than the one previously admitted, with a limit of 20&#xD;
      ng/mL (50 nmol/L) to define a vitamin D deficiency and a limit of 30 ng/mL (75 nmol/L) to&#xD;
      define vitamin D insufficiency.&#xD;
&#xD;
      Recommendations for Vit D supplementation in healthy children were updated in France in 2012.&#xD;
      The invariable supplementation of infants and toddlers is efficient since deficiency-related&#xD;
      rickets have almost disappeared; however there is very few information in ill children&#xD;
      populations.&#xD;
&#xD;
      Vit D supplementation tolerance is usually considered as good and over-dosage risks are low,&#xD;
      however these studies were conducted more than 30 years ago, and as far as we know, there is&#xD;
      no study about calcium urinary excretion kinetics after intake of a 100 000 IU vial of&#xD;
      cholecalciferol (Uvedose®). When 25 OH vitamin D serum concentrations exceeds 200 ng/mL,&#xD;
      which is very rare in daily practice, toxic effects of Vit D may theoretically be observed,&#xD;
      particularly hypercalcemia and hypercalciuria.&#xD;
&#xD;
      Vitamin D deficit is very common in children with chronic kidney disease (CKD) with a 50 to&#xD;
      92% prevalence depending on the studies; it it is a risk factor for secondary&#xD;
      hyperparathyroidism.&#xD;
&#xD;
      Although international guidelines regarding the care of CKD children recommend 25 OH vitamin&#xD;
      D serum concentrations over 75 nmol/L, there are no practical recommendations in terms of&#xD;
      dose and frequency of native Vit D treatment.&#xD;
&#xD;
      Therefore, the objectives of the present study has are the following:&#xD;
&#xD;
        -  to validate prospectively the efficacy of our service usual care for Vit D&#xD;
           supplementation of children and adolescents seen in the paediatric nephrology&#xD;
           department.&#xD;
&#xD;
        -  and to study the effect of Vit D supplementation (100 000 IU vial of cholecalciferol) on&#xD;
           calciuria in these patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">October 2017</completion_date>
  <primary_completion_date type="Actual">October 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy of usual vitamin D supplementation</measure>
    <time_frame>Day 60</time_frame>
    <description>The 25 OH vitamin D serum concentration will be measured at inclusion (before treatment intake) and 2 months after supplementation. No extra blood intake is programmed since this parameter is always measured in this population. The main evaluation criterion is defined as a 25 OH vitamin D serum concentration over 75 nmol/l at month 2. This defines the success of supplementation. The failure is defined as a 25 OH vitamin D serum concentration under 75 nmol/l at month 2.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Kinetics of calciuria after a 100 000 IU vial of cholecalciferol</measure>
    <time_frame>Day 0, day 1, day 2, day 3, day 4, day 7 after treatment intake.</time_frame>
    <description>Calciuria (absolute and normalized with the calculation of the ratio urinary calcium/creatinine) will be measured on the first morning urine at those time points after each vial intake. Measurements will be made in the unique local laboratory chosen by each patient. Thus the lab will be different between patients but must remain the same for each patient.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Chronic Kidney Disease</condition>
  <condition>Renal Transplantation</condition>
  <condition>Nephrotic Syndrome</condition>
  <arm_group>
    <arm_group_label>Usual vitamin D supplementation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cholecalciferol vial (100 000 UI)</intervention_name>
    <description>VISIT 1:&#xD;
Patient &gt; 60 kg and initial 25OHD serum concentration &lt; 25nmol/L : prescription of 4 vials to be taken every 2 weeks between 25 and 50 nmol/L: prescription of 3 vials to be taken every 2 weeks between 50 and 75 nmol/L: prescription of 2 vials to be taken every 2 weeks Patient between 20 and 60 kg and initial 25OHD serum concentration &lt; 25nmol/L: prescription of 2 vials to be taken every month between 25 and 50 nmol/L: prescription of 2 vials to be taken every 6 weeks between 50 and 75 nmol/L: prescription of 1 single vial Patient &lt; 20 kg and initial 25OHD serum concentration &lt; 75 nmol/L: prescription of 1 single vial&#xD;
A local lab will performed urinary dosage of calciuria and creatininuria:&#xD;
at days 0, 1, 2, 3, 4 and 7 after the first intake of a 25OHD vial&#xD;
at days 0, 2 and 4 after other intakes (when applicable)&#xD;
VISIT 2:&#xD;
25OHD serum concentration will then be dosed at month 2 after visit 1</description>
    <arm_group_label>Usual vitamin D supplementation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age : between [18 mo et 18 yo[&#xD;
&#xD;
          -  Patients seen in the paediatric nephrology service and having :&#xD;
&#xD;
               -  Chronic kidney disease&#xD;
&#xD;
               -  Renal transplant&#xD;
&#xD;
               -  Stable nephrotic syndrome (i.e., normal protidemia at inclusion)&#xD;
&#xD;
          -  Initial 25 OH vitamin D concentration &lt; 75nmol/l&#xD;
&#xD;
          -  Patient agree to participate (if old enough to give his agreement) and written&#xD;
             informed consent signed by parents&#xD;
&#xD;
          -  Patients affiliated within the French universal healthcare system&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        - Contraindication to 100 000 IU Uvedose® treatment (according to the Summary of Product&#xD;
        Characteristics: known hypersensitivity to vitamin D or hypercalcemia, hypercalciuria or&#xD;
        nephrolithiasis).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Justine Bacchetta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>HCL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre de Référence des Maladies Rénales Rares - Hospices Civils de Lyon - Service de Néphrologie et Rhumatologie Pédiatriques - Hôpital Femme Mère Enfant</name>
      <address>
        <city>Bron</city>
        <zip>69500</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>September 10, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>July 17, 2018</last_update_submitted>
  <last_update_submitted_qc>July 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vitamin D, Calciuria, Paediatrics, Nephrology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Nephrotic Syndrome</mesh_term>
    <mesh_term>Nephrosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholecalciferol</mesh_term>
    <mesh_term>Vitamin D</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02238418
org study id: 2013-812
secondary id: 2013-002710-13
nct id: NCT02238418
lead sponsor: 
has dmc: No
Vitamin D is not seen anymore only as a phosphocalcic and bone hormone, but also as having an
      effect on global health (anti-infective, anti-inflammatory, anti-tumour roles and
      cardiovascular protection).

      Until recently, vitamin D repletion was defined as the minimal concentration that enables the
      prevention of rickets in children and osteomalacia in adults, i.e, approximately 8 ng/mL (20
      nmol/L). However, most of the international experts agree to set minimal threshold of 25 OH
      vitamin D serum concentration, higher than the one previously admitted, with a limit of 20
      ng/mL (50 nmol/L) to define a vitamin D deficiency and a limit of 30 ng/mL (75 nmol/L) to
      define vitamin D insufficiency.

      Recommendations for Vit D supplementation in healthy children were updated in France in 2012.
      The invariable supplementation of infants and toddlers is efficient since deficiency-related
      rickets have almost disappeared; however there is very few information in ill children
      populations.

      Vit D supplementation tolerance is usually considered as good and over-dosage risks are low,
      however these studies were conducted more than 30 years ago, and as far as we know, there is
      no study about calcium urinary excretion kinetics after intake of a 100 000 IU vial of
      cholecalciferol (Uvedose®). When 25 OH vitamin D serum concentrations exceeds 200 ng/mL,
      which is very rare in daily practice, toxic effects of Vit D may theoretically be observed,
      particularly hypercalcemia and hypercalciuria.

      Vitamin D deficit is very common in children with chronic kidney disease (CKD) with a 50 to
      92% prevalence depending on the studies; it it is a risk factor for secondary
      hyperparathyroidism.

      Although international guidelines regarding the care of CKD children recommend 25 OH vitamin
      D serum concentrations over 75 nmol/L, there are no practical recommendations in terms of
      dose and frequency of native Vit D treatment.

      Therefore, the objectives of the present study has are the following:

        -  to validate prospectively the efficacy of our service usual care for Vit D
           supplementation of children and adolescents seen in the paediatric nephrology
           department.

        -  and to study the effect of Vit D supplementation (100 000 IU vial of cholecalciferol) on
           calciuria in these patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Efficacy of usual vitamin D supplementation
time frame: Day 60
description: The 25 OH vitamin D serum concentration will be measured at inclusion (before treatment intake) and 2 months after supplementation. No extra blood intake is programmed since this parameter is always measured in this population. The main evaluation criterion is defined as a 25 OH vitamin D serum concentration over 75 nmol/l at month 2. This defines the success of supplementation. The failure is defined as a 25 OH vitamin D serum concentration under 75 nmol/l at month 2.
measure: Kinetics of calciuria after a 100 000 IU vial of cholecalciferol
time frame: Day 0, day 1, day 2, day 3, day 4, day 7 after treatment intake.
description: Calciuria (absolute and normalized with the calculation of the ratio urinary calcium/creatinine) will be measured on the first morning urine at those time points after each vial intake. Measurements will be made in the unique local laboratory chosen by each patient. Thus the lab will be different between patients but must remain the same for each patient.
arm group label: Usual vitamin D supplementation
arm group type: Experimental
intervention type: Drug
intervention name: Cholecalciferol vial (100 000 UI)
description: VISIT 1:
Patient > 60 kg and initial 25OHD serum concentration < 25nmol/L : prescription of 4 vials to be taken every 2 weeks between 25 and 50 nmol/L: prescription of 3 vials to be taken every 2 weeks between 50 and 75 nmol/L: prescription of 2 vials to be taken every 2 weeks Patient between 20 and 60 kg and initial 25OHD serum concentration < 25nmol/L: prescription of 2 vials to be taken every month between 25 and 50 nmol/L: prescription of 2 vials to be taken every 6 weeks between 50 and 75 nmol/L: prescription of 1 single vial Patient < 20 kg and initial 25OHD serum concentration < 75 nmol/L: prescription of 1 single vial
A local lab will performed urinary dosage of calciuria and creatininuria:
at days 0, 1, 2, 3, 4 and 7 after the first intake of a 25OHD vial
at days 0, 2 and 4 after other intakes (when applicable)
VISIT 2:
25OHD serum concentration will then be dosed at month 2 after visit 1
arm group label: Usual vitamin D supplementation
criteria: 
gender: All
minimum age: 18 Months
maximum age: 18 Years
healthy volunteers: No
last name: Justine Bacchetta, MD
role: Principal Investigator
affiliation: HCL
facility: 
country: France
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Cholecalciferol
mesh term: Vitamin D
sharing ipd: No