<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/NCT01713231</url>
  </required_header>
  <id_info>
    <org_study_id>A02-M14-12A</org_study_id>
    <nct_id>NCT01713231</nct_id>
  </id_info>
  <brief_title>Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta</brief_title>
  <official_title>Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Louis-Nicolas Veilleux Ph.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shriners Hospitals for Children</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  Overall Objective: To test the hypothesis that oral vitamin D supplementation at higher&#xD;
           than currently prescribed doses has a beneficial effect on the skeleton of young&#xD;
           patients with osteogenesis imperfecta (OI).&#xD;
&#xD;
        -  Specific Aims: 1. To determine whether 12 months of high-dose vitamin D supplementation,&#xD;
           compared to standard-dose vitamin D supplementation, increases areal bone mineral&#xD;
           density z-scores at the lumbar spine. 2. To examine the effectiveness of high-dose&#xD;
           vitamin D supplementation to increase trabecular and cortical bone mineral density at&#xD;
           the radius. 3. To examine whether high-dose vitamin D supplementation has an effect on&#xD;
           physiological determinants of bone mass (parathyroid hormone, activity of bone&#xD;
           metabolism, muscle function).&#xD;
&#xD;
        -  Background: In a preliminary cross-sectional study of 282 OI patients we observed an&#xD;
           inverse relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels&#xD;
           and a positive relationship between circulating levels of 25-hydroxyvitamin D and lumbar&#xD;
           spine areal bone mineral density z-scores. This suggested that high-dose vitamin D&#xD;
           supplementation would have a beneficial effect on bone density. Most OI patients&#xD;
           currently receive oral vitamin D supplementation of 400 International Units per day, but&#xD;
           doses of 2000 International Units per day are safe and have been shown to be beneficial&#xD;
           in studies on healthy adolescents.&#xD;
&#xD;
        -  Study Design: This is a parallel-group double-blind randomized controlled trial of 12&#xD;
           months duration on 60 children and adolescents aged 6 to 19 years with a clinical&#xD;
           diagnosis of OI. One group of 30 participants will be randomized to receive vitamin D3&#xD;
           at a dose of 2000 international units per day ('high-dose group'). The other group of 30&#xD;
           participants will be randomized to receive vitamin D3 at a dose of 400 international&#xD;
           units per day ('standard-dose group'). Randomization will be stratified according to&#xD;
           pubertal status and bisphosphonate treatment status.&#xD;
&#xD;
        -  Clinical Relevance: The proposed study aims at direct improvements in the care of OI&#xD;
           patients. If a simple and low-cost 'intervention' such as high-dose vitamin D&#xD;
           supplementation can be shown to be effective in relieving some of the disease burden&#xD;
           associated with OI, the benefit to OI patients worldwide would be substantial.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">March 2013</primary_completion_date>
  <phase>Phase 4</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>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in areal bone mineral density z-score of the lumbar spine</measure>
    <time_frame>at baseline and 12 months</time_frame>
    <description>LS-aBMD z-score will be used as the primary outcome.The lumbar spine is the standard site of measurement both in the clinical follow up of OI patients .</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in trabecular and cortical volumetric bone mineral density z-scores at the radius, as measured by pQCT, relative to baseline.</measure>
    <time_frame>at baseline and at 12 months</time_frame>
    <description>Trabecular bone is analyzed at the distal radial metaphysis ('4% site'). Cortical bone is analyzed at the radial diaphysis ('65% site').</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Percentage change in lower extremity muscle power per body weight, as measured by jumping mechanography, relative to baseline.</measure>
    <time_frame>baseline and 12 months</time_frame>
    <description>A countermovement jump to maximal height ('single two-legged jump') will be evaluated. In patients who are unable to jump, the heel-rise test will be used to determine muscle power.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Osteogenesis Imperfecta</condition>
  <arm_group>
    <arm_group_label>standard-dose vitamin D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>one group of 30 participants will be randomized to receive vitamin D3 at a dose of 400 international units per day ('standard-dose group').</description>
  </arm_group>
  <arm_group>
    <arm_group_label>high-dose vitamin D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One group of 30 participants will be randomized to receive vitamin D3 at a dose of 2000 international units per day ('high-dose group').</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>standard-dose vitamin D (400IU per day)</intervention_name>
    <arm_group_label>standard-dose vitamin D</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>high-dose vitamin D (2000 IU per day)</intervention_name>
    <arm_group_label>high-dose vitamin D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of OI of any type.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any condition that renders bone density measurements at the lumbar spine impossible.&#xD;
             An example for this is prior spinal fusion surgery.&#xD;
&#xD;
          -  Bisphosphonate therapy for less than two years duration.&#xD;
&#xD;
          -  Use of medication, other than bisphosphonates, known to affect bone metabolism or&#xD;
             25OHD serum concentrations. Examples are anti-epileptics, active vitamin D&#xD;
             metabolites, corticosteroids and thyroid hormones.&#xD;
&#xD;
          -  Liver and renal disease known to interfere with vitamin D metabolism.&#xD;
&#xD;
          -  Any other disorder of calcium and phosphate metabolism (apart from vitamin D&#xD;
             deficiency) that might interfere with PTH.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>19 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shriners Hospitals for Children-Canada</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H3G1A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>October 21, 2012</study_first_submitted>
  <study_first_submitted_qc>October 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <last_update_submitted>September 8, 2014</last_update_submitted>
  <last_update_submitted_qc>September 8, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 9, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Shriners Hospitals for Children</investigator_affiliation>
    <investigator_full_name>Louis-Nicolas Veilleux Ph.D.</investigator_full_name>
    <investigator_title>postdoctoral fellow</investigator_title>
  </responsible_party>
  <keyword>osteogenesis imperfecta</keyword>
  <keyword>high-dose vitamin D</keyword>
  <keyword>bone density</keyword>
  <keyword>muscle function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteogenesis Imperfecta</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/NCT01713231
org study id: A02-M14-12A
nct id: NCT01713231
lead sponsor: 
has dmc: Yes
-  Overall Objective: To test the hypothesis that oral vitamin D supplementation at higher
           than currently prescribed doses has a beneficial effect on the skeleton of young
           patients with osteogenesis imperfecta (OI).

        -  Specific Aims: 1. To determine whether 12 months of high-dose vitamin D supplementation,
           compared to standard-dose vitamin D supplementation, increases areal bone mineral
           density z-scores at the lumbar spine. 2. To examine the effectiveness of high-dose
           vitamin D supplementation to increase trabecular and cortical bone mineral density at
           the radius. 3. To examine whether high-dose vitamin D supplementation has an effect on
           physiological determinants of bone mass (parathyroid hormone, activity of bone
           metabolism, muscle function).

        -  Background: In a preliminary cross-sectional study of 282 OI patients we observed an
           inverse relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels
           and a positive relationship between circulating levels of 25-hydroxyvitamin D and lumbar
           spine areal bone mineral density z-scores. This suggested that high-dose vitamin D
           supplementation would have a beneficial effect on bone density. Most OI patients
           currently receive oral vitamin D supplementation of 400 International Units per day, but
           doses of 2000 International Units per day are safe and have been shown to be beneficial
           in studies on healthy adolescents.

        -  Study Design: This is a parallel-group double-blind randomized controlled trial of 12
           months duration on 60 children and adolescents aged 6 to 19 years with a clinical
           diagnosis of OI. One group of 30 participants will be randomized to receive vitamin D3
           at a dose of 2000 international units per day ('high-dose group'). The other group of 30
           participants will be randomized to receive vitamin D3 at a dose of 400 international
           units per day ('standard-dose group'). Randomization will be stratified according to
           pubertal status and bisphosphonate treatment status.

        -  Clinical Relevance: The proposed study aims at direct improvements in the care of OI
           patients. If a simple and low-cost 'intervention' such as high-dose vitamin D
           supplementation can be shown to be effective in relieving some of the disease burden
           associated with OI, the benefit to OI patients worldwide would be substantial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in areal bone mineral density z-score of the lumbar spine
time frame: at baseline and 12 months
description: LS-aBMD z-score will be used as the primary outcome.The lumbar spine is the standard site of measurement both in the clinical follow up of OI patients .
measure: Change in trabecular and cortical volumetric bone mineral density z-scores at the radius, as measured by pQCT, relative to baseline.
time frame: at baseline and at 12 months
description: Trabecular bone is analyzed at the distal radial metaphysis ('4% site'). Cortical bone is analyzed at the radial diaphysis ('65% site').
measure: Percentage change in lower extremity muscle power per body weight, as measured by jumping mechanography, relative to baseline.
time frame: baseline and 12 months
description: A countermovement jump to maximal height ('single two-legged jump') will be evaluated. In patients who are unable to jump, the heel-rise test will be used to determine muscle power.
arm group label: standard-dose vitamin D
arm group type: Active Comparator
description: one group of 30 participants will be randomized to receive vitamin D3 at a dose of 400 international units per day ('standard-dose group').
arm group label: high-dose vitamin D
arm group type: Experimental
description: One group of 30 participants will be randomized to receive vitamin D3 at a dose of 2000 international units per day ('high-dose group').
intervention type: Dietary Supplement
intervention name: standard-dose vitamin D (400IU per day)
arm group label: standard-dose vitamin D
intervention type: Dietary Supplement
intervention name: high-dose vitamin D (2000 IU per day)
arm group label: high-dose vitamin D
criteria: 
gender: All
minimum age: 6 Years
maximum age: 19 Years
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor-Investigator
investigator affiliation: Shriners Hospitals for Children
investigator full name: Louis-Nicolas Veilleux Ph.D.
investigator title: postdoctoral fellow
mesh term: Osteogenesis Imperfecta
mesh term: Vitamin D
mesh term: Ergocalciferols
mesh term: Cholecalciferol
mesh term: Vitamins