<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/NCT03820518</url>
  </required_header>
  <id_info>
    <org_study_id>JS-1824</org_study_id>
    <nct_id>NCT03820518</nct_id>
  </id_info>
  <brief_title>Using Different Doses of Active Vitamin D Combined With Neutral Phosphate in Children With X-linked Hypophosphatemia</brief_title>
  <official_title>Comparing the Effectiveness of High or Low Dose of Active Vitamin D Combined With Neutral Phosphate in Children With X-linked Hypophosphatemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      X-linked hypophosphatemia (XLH) is the most common form of heritable rickets. Current&#xD;
      treatments include active vitamin D metabolites (e.g. calcitriol) and phosphate salts. There&#xD;
      is no consistent weight-based dosing of calcitriol and phosphate now. The primary objective&#xD;
      of this study is to establish the efficacy of different dose of calcitriol combined with&#xD;
      neutral phosphate in children with XLH.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline to Post-treatment in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total Score</measure>
    <time_frame>Baseline, Month 12, 24</time_frame>
    <description>RSS range from 0 to 10, and higher RSS represent severer rickets. It is consisted of score of worst wrist (0-4) and worst knee (0-6).&#xD;
WRIST-score both radius and ulna separately-2 bones × 2 points = 4 points possible KNEE-score both femur and tibia separately Multiply the grade in A by the multiplier in B for each bone, then add femur and tibia scores together A: Grade&#xD;
1 2 3 B: Multiplier Portion of growth plate affected 0.5 ≤ 1 condyle or plateau&#xD;
2 condyles or plateaus&#xD;
bones × 1 point × 3 points = 6 points possible Total: 10 points possible Reference:Thacher, T. Radiographic scoring method for the assessment of the severity of nutritional rickets[J]. Journal of Tropical Pediatrics, 2000, 46(3):132-139.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score</measure>
    <time_frame>Baseline, Month 12, 24</time_frame>
    <description>RSS range from 0 to 10, and higher RSS represent severer rickets. It is consisted of score of worst wrist (0-4) and worst knee (0-6).&#xD;
WRIST-score both radius and ulna separately-2 bones × 2 points = 4 points possible KNEE-score both femur and tibia separately Multiply the grade in A by the multiplier in B for each bone, then add femur and tibia scores together A: Grade&#xD;
1 2 3 B: Multiplier Portion of growth plate affected 0.5 ≤ 1 condyle or plateau&#xD;
2 condyles or plateaus&#xD;
bones × 1 point × 3 points = 6 points possible Total: 10 points possible Reference:Thacher, T. Radiographic scoring method for the assessment of the severity of nutritional rickets[J]. Journal of Tropical Pediatrics, 2000, 46(3):132-139.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Growth Velocity</measure>
    <time_frame>Baseline, Month 12, 24</time_frame>
    <description>Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Serum Total Alkaline Phosphatase (TALP) Levels</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>Changes From Baseline to Post-treatment in serum ALP</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in serum Carboxy-terminal Collagen Crosslinks (CTX) Levels</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>Changes From Baseline to Post-treatment in serum CTX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Serum Phosphorus Levels</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>Changes From Baseline to Post-treatment in Serum Phosphorus Levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Severity of Dental Abscess</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>The frequency and number of dental abscess will be collected by self-report and examed by investigators</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Severity of Bone Pain as Measured by Visual Analog Pain Scales</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>Visual Analog Pain Scales (VAS) range from 0-10, and higher score represents severer pain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Severity of Leg Deformities</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>The longest distance between two sides of thighs, knees, shanks and ankles are measured to evaluate the severity of leg deformities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Serum Osteocalcin Levels</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>Changes From Baseline to Post-treatment in Serum Osteocalcin Levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Height</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>Changes From Baseline to Post-treatment in Height</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information System</measure>
    <time_frame>Baseline, Month 3, 6, 12, 18, 24</time_frame>
    <description>Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information System</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>X-linked Hypophosphatemia</condition>
  <arm_group>
    <arm_group_label>High-dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Receiving 60 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Low-dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Receiving 20 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcitriol</intervention_name>
    <arm_group_label>High-dose</arm_group_label>
    <arm_group_label>Low-dose</arm_group_label>
    <other_name>Elementary phosphorus</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, aged 1-12 years, inclusive&#xD;
&#xD;
          -  Diagnosis of XLH by clinical features: serum phosphorus level &lt; 2.5 mg/dl; ALP?; RSS&#xD;
             total score ≥2; bowed legs; short stature; family history with appropriate X-linked&#xD;
             inheritance&#xD;
&#xD;
          -  Meet at least one of the following: confirmed Phosphate regulating gene with homology&#xD;
             to endopeptidases located on the X chromosome (PHEX) mutation in the participant, or&#xD;
             serum FGF23 level &gt;30 pg/ml (Kainos assay)&#xD;
&#xD;
          -  Willing to participate the study, and provide an informed consent&#xD;
&#xD;
          -  Able to complete all aspects of study and adhere to the visit schedule&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of growth hormone within 12 months before first visit&#xD;
&#xD;
          -  Height &gt;50 percentile for age and sex specific data&#xD;
&#xD;
          -  Presence of nephrocalcinosis or nephrolithiasis&#xD;
&#xD;
          -  Serum intact parathyroid hormone level&gt;170 pg/ml&#xD;
&#xD;
          -  Plan to receive orthopaedic surgery in 12 months&#xD;
&#xD;
          -  Poor compliance&#xD;
&#xD;
          -  Use of gonadotropin-releasing hormone therapy right now&#xD;
&#xD;
          -  Use of aluminium hydroxide, steroid, acetazolamide or thiazide drugs within 7 days&#xD;
             before first visit&#xD;
&#xD;
          -  Not be fit to participant in the study, by the judgement of investigators&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Weibo Xia, MD</last_name>
    <phone>+86 13501002126</phone>
    <email>xiaweibo8301@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Endocrinology, Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Weibo Xia, MD</last_name>
      <phone>+86 13501002126</phone>
      <email>xiaweibo8301@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>January 28, 2019</last_update_submitted>
  <last_update_submitted_qc>January 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Familial Hypophosphatemic Rickets</mesh_term>
    <mesh_term>Hypophosphatemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcitriol</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/NCT03820518
org study id: JS-1824
nct id: NCT03820518
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
X-linked hypophosphatemia (XLH) is the most common form of heritable rickets. Current
      treatments include active vitamin D metabolites (e.g. calcitriol) and phosphate salts. There
      is no consistent weight-based dosing of calcitriol and phosphate now. The primary objective
      of this study is to establish the efficacy of different dose of calcitriol combined with
      neutral phosphate in children with XLH.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline to Post-treatment in Severity of Rickets as Measured by Rickets Severity Score (RSS) Total Score
time frame: Baseline, Month 12, 24
description: RSS range from 0 to 10, and higher RSS represent severer rickets. It is consisted of score of worst wrist (0-4) and worst knee (0-6).
WRIST-score both radius and ulna separately-2 bones × 2 points = 4 points possible KNEE-score both femur and tibia separately Multiply the grade in A by the multiplier in B for each bone, then add femur and tibia scores together A: Grade
1 2 3 B: Multiplier Portion of growth plate affected 0.5 ≤ 1 condyle or plateau
2 condyles or plateaus
bones × 1 point × 3 points = 6 points possible Total: 10 points possible Reference:Thacher, T. Radiographic scoring method for the assessment of the severity of nutritional rickets[J]. Journal of Tropical Pediatrics, 2000, 46(3):132-139.
measure: Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score
time frame: Baseline, Month 12, 24
description: RSS range from 0 to 10, and higher RSS represent severer rickets. It is consisted of score of worst wrist (0-4) and worst knee (0-6).
WRIST-score both radius and ulna separately-2 bones × 2 points = 4 points possible KNEE-score both femur and tibia separately Multiply the grade in A by the multiplier in B for each bone, then add femur and tibia scores together A: Grade
1 2 3 B: Multiplier Portion of growth plate affected 0.5 ≤ 1 condyle or plateau
2 condyles or plateaus
bones × 1 point × 3 points = 6 points possible Total: 10 points possible Reference:Thacher, T. Radiographic scoring method for the assessment of the severity of nutritional rickets[J]. Journal of Tropical Pediatrics, 2000, 46(3):132-139.
measure: Changes From Baseline to Post-treatment in Growth Velocity
time frame: Baseline, Month 12, 24
description: Changes From Baseline to Post-treatment in Severity of Rickets as Measured by RSS Wrist and Knee Score
measure: Changes From Baseline to Post-treatment in Serum Total Alkaline Phosphatase (TALP) Levels
time frame: Baseline, Month 3, 6, 12, 18, 24
description: Changes From Baseline to Post-treatment in serum ALP
measure: Changes From Baseline to Post-treatment in serum Carboxy-terminal Collagen Crosslinks (CTX) Levels
time frame: Baseline, Month 3, 6, 12, 18, 24
description: Changes From Baseline to Post-treatment in serum CTX
measure: Changes From Baseline to Post-treatment in Serum Phosphorus Levels
time frame: Baseline, Month 3, 6, 12, 18, 24
description: Changes From Baseline to Post-treatment in Serum Phosphorus Levels
measure: Changes From Baseline to Post-treatment in Severity of Dental Abscess
time frame: Baseline, Month 3, 6, 12, 18, 24
description: The frequency and number of dental abscess will be collected by self-report and examed by investigators
measure: Changes From Baseline to Post-treatment in Severity of Bone Pain as Measured by Visual Analog Pain Scales
time frame: Baseline, Month 3, 6, 12, 18, 24
description: Visual Analog Pain Scales (VAS) range from 0-10, and higher score represents severer pain
measure: Changes From Baseline to Post-treatment in Severity of Leg Deformities
time frame: Baseline, Month 3, 6, 12, 18, 24
description: The longest distance between two sides of thighs, knees, shanks and ankles are measured to evaluate the severity of leg deformities.
measure: Changes From Baseline to Post-treatment in Serum Osteocalcin Levels
time frame: Baseline, Month 3, 6, 12, 18, 24
description: Changes From Baseline to Post-treatment in Serum Osteocalcin Levels
measure: Changes From Baseline to Post-treatment in Height
time frame: Baseline, Month 3, 6, 12, 18, 24
description: Changes From Baseline to Post-treatment in Height
measure: Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information System
time frame: Baseline, Month 3, 6, 12, 18, 24
description: Changes From Baseline to Post-treatment in Quality of Life as Measured by Patient-reported Outcomes Measurement Information System
arm group label: High-dose
arm group type: Experimental
description: Receiving 60 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.
arm group label: Low-dose
arm group type: Experimental
description: Receiving 20 ng/kg/day of calcitriol and 30 mg/kg/day of elemental phosphorus.
intervention type: Drug
intervention name: Calcitriol
arm group label: High-dose
arm group label: Low-dose
other name: Elementary phosphorus
criteria: 
gender: All
minimum age: 1 Year
maximum age: 12 Years
healthy volunteers: No
last name: Weibo Xia, MD
phone: +86 13501002126
email: xiaweibo8301@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Familial Hypophosphatemic Rickets
mesh term: Hypophosphatemia
mesh term: Calcitriol
sharing ipd: No