<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/NCT03748966</url>
  </required_header>
  <id_info>
    <org_study_id>2016P001000</org_study_id>
    <nct_id>NCT03748966</nct_id>
  </id_info>
  <brief_title>Calcitriol Monotherapy for X-Linked Hypophosphatemia</brief_title>
  <official_title>Calcitriol Monotherapy for X-Linked Hypophosphatemia: Effects on Mineral Ions, Growth and Skeletal Parameters</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Children and adults with XLH recruited will be treated with calcitriol alone (without&#xD;
      phosphate supplementation) for one year, during which the calcitriol dose will be escalated&#xD;
      during the first 3 months of therapy. The investigators hypothesize that treatment of adults&#xD;
      and children with XLH alone will improve serum phosphate levels and skeletal mineralization&#xD;
      without causing an increase in kidney calcifications. The study will also examine if&#xD;
      calcitriol therapy will improve growth in children.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 28, 2019</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">March 2023</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Adults or children (age 3-17) with X-linked hypophosphatemia (XLH) will be enrolled the study. All research subjects will be treated with optimized doses of calcitriol alone (without phosphate supplementation) for one year.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in serum phosphate in adults and children with XLH</measure>
    <time_frame>up to 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in TmP/GFR in adults and children with XLH</measure>
    <time_frame>up to 12 months</time_frame>
    <description>a measure of kidney resorption of phosphate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rickets score for children with XLH</measure>
    <time_frame>up to 12 months</time_frame>
    <description>a score of rickets severity determined by reading x-rays of wrists and knees (10 point Thacher score with 0 being normal and 10 being severe)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in nephrocalcinosis grade</measure>
    <time_frame>up to 12 months</time_frame>
    <description>determine if there is change in amount of calcifications in the kidneys: graded from grade 0 (normal) to grade IV (stone formation, solitary focus of echos at the tip of the renal pyramid)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Growth in children with XLH</measure>
    <time_frame>up to 12 months</time_frame>
    <description>Z-score of growth</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>X-linked Hypophosphatemia</condition>
  <condition>Hypophosphatemic Rickets</condition>
  <condition>Hypophosphatemic Rickets, X-Linked Dominant</condition>
  <arm_group>
    <arm_group_label>Adults with XLH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Adults with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Children with XLH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Children (age 3-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Calcitriol</intervention_name>
    <description>Adults and children (age 3-17) with X-linked hypophosphatemia will be treated with calcitriol therapy without phosphate supplementation. Doses of calcitriol will be escalated and optimized in the first three months of the study. Calcitriol is an oral medication taken once a day.</description>
    <arm_group_label>Adults with XLH</arm_group_label>
    <arm_group_label>Children with XLH</arm_group_label>
    <other_name>1,25 dihydroxyvitamin D</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of XLH with family history excluding male-to-male transmission, or&#xD;
             positive genotype for PHEX mutation&#xD;
&#xD;
          -  Serum PTH levels less than 1.5x the upper limit of normal&#xD;
&#xD;
          -  Serum calcium levels less than 10.0 mg/dl&#xD;
&#xD;
          -  eGFR &gt;= 60 mL/min/1.73m2&#xD;
&#xD;
          -  25(OH) vitamin D level &gt;= 20 ng/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy to calcitriol&#xD;
&#xD;
          -  Pregnancy or breast feeding&#xD;
&#xD;
          -  Use of skeletally active agents such as bisphosphonates, teriparatide, SERMS, hormone&#xD;
             replacement therapy and progesterone-only contraceptive agents (combination oral&#xD;
             contraceptive use in premenopausal women is not an exclusion criterion).&#xD;
&#xD;
          -  Unwilling or unable to stop therapy with calcitriol and phosphate therapy for two&#xD;
             weeks prior to study&#xD;
&#xD;
          -  Therapy with cinacalcet within the past two weeks&#xD;
&#xD;
          -  Current use of growth hormone therapy&#xD;
&#xD;
          -  Use of diuretics or medications that alter renal handling of mineral ions.&#xD;
&#xD;
          -  Use of glucocorticoids for more than 14 days in the past 12 months with the exception&#xD;
             of inhaled agents.&#xD;
&#xD;
          -  History of malignancy except basal and squamous cell carcinoma of the skin.&#xD;
&#xD;
          -  Significant history of psychiatric disease per DSM-5.&#xD;
&#xD;
          -  Substance use disorder per DSM-5.&#xD;
&#xD;
          -  Significant cardiopulmonary disease (unstable CAD or stage D ACC/AHA heart failure).&#xD;
&#xD;
          -  Absence of laboratory values for serum calcium, phosphate and creatinine in the 24&#xD;
             months prior to enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>3 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eva Liu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital and Brigham and Women's Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Eva S Liu, MD</last_name>
    <phone>16175255412</phone>
    <email>esliu@bwh.harvard.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marie Demay, MD</last_name>
    <phone>16177263273</phone>
    <email>demay@helix.mgh.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eva Liu, MD</last_name>
      <phone>617-525-5412</phone>
      <email>esliu@bwh.harvard.edu</email>
    </contact>
    <contact_backup>
      <last_name>Marie Demay, MD</last_name>
      <phone>6177263273</phone>
      <email>demay@helix.mgh.harvard.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Liu ES, Martins JS, Raimann A, Chae BT, Brooks DJ, Jorgetti V, Bouxsein ML, Demay MB. 1,25-Dihydroxyvitamin D Alone Improves Skeletal Growth, Microarchitecture, and Strength in a Murine Model of XLH, Despite Enhanced FGF23 Expression. J Bone Miner Res. 2016 May;31(5):929-39. doi: 10.1002/jbmr.2783. Epub 2016 Feb 2.</citation>
    <PMID>26751835</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 21, 2018</study_first_posted>
  <last_update_submitted>March 16, 2022</last_update_submitted>
  <last_update_submitted_qc>March 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Eva Liu</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>XLH</keyword>
  <keyword>calcitriol</keyword>
  <keyword>x-linked hypophosphatemia</keyword>
  <keyword>rickets</keyword>
  <keyword>1,25 dihydroxyvitamin D</keyword>
  <keyword>bone disorder</keyword>
  <keyword>rare bone disease</keyword>
  <keyword>vitamin D</keyword>
  <keyword>hypophosphatemic rickets</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rickets</mesh_term>
    <mesh_term>Familial Hypophosphatemic Rickets</mesh_term>
    <mesh_term>Rickets, Hypophosphatemic</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>
    <mesh_term>Dihydroxycholecalciferols</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/NCT03748966
org study id: 2016P001000
nct id: NCT03748966
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Children and adults with XLH recruited will be treated with calcitriol alone (without
      phosphate supplementation) for one year, during which the calcitriol dose will be escalated
      during the first 3 months of therapy. The investigators hypothesize that treatment of adults
      and children with XLH alone will improve serum phosphate levels and skeletal mineralization
      without causing an increase in kidney calcifications. The study will also examine if
      calcitriol therapy will improve growth in children.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Adults or children (age 3-17) with X-linked hypophosphatemia (XLH) will be enrolled the study. All research subjects will be treated with optimized doses of calcitriol alone (without phosphate supplementation) for one year.
primary purpose: Treatment
masking: None (Open Label)
measure: Change from baseline in serum phosphate in adults and children with XLH
time frame: up to 12 months
measure: Change from baseline in TmP/GFR in adults and children with XLH
time frame: up to 12 months
description: a measure of kidney resorption of phosphate
measure: Rickets score for children with XLH
time frame: up to 12 months
description: a score of rickets severity determined by reading x-rays of wrists and knees (10 point Thacher score with 0 being normal and 10 being severe)
measure: Change from baseline in nephrocalcinosis grade
time frame: up to 12 months
description: determine if there is change in amount of calcifications in the kidneys: graded from grade 0 (normal) to grade IV (stone formation, solitary focus of echos at the tip of the renal pyramid)
measure: Growth in children with XLH
time frame: up to 12 months
description: Z-score of growth
arm group label: Adults with XLH
arm group type: Experimental
description: Adults with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year
arm group label: Children with XLH
arm group type: Experimental
description: Children (age 3-17) with X-linked hypophosphatemia will be treated with optimized doses of calcitriol (without phosphate supplementation) for one year
intervention type: Drug
intervention name: Calcitriol
description: Adults and children (age 3-17) with X-linked hypophosphatemia will be treated with calcitriol therapy without phosphate supplementation. Doses of calcitriol will be escalated and optimized in the first three months of the study. Calcitriol is an oral medication taken once a day.
arm group label: Adults with XLH
arm group label: Children with XLH
other name: 1,25 dihydroxyvitamin D
criteria: 
gender: All
minimum age: 3 Years
maximum age: 70 Years
healthy volunteers: No
last name: Eva Liu, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital and Brigham and Women's Hospital
last name: Eva S Liu, MD
phone: 16175255412
email: esliu@bwh.harvard.edu
last name: Marie Demay, MD
phone: 16177263273
email: demay@helix.mgh.harvard.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Liu ES, Martins JS, Raimann A, Chae BT, Brooks DJ, Jorgetti V, Bouxsein ML, Demay MB. 1,25-Dihydroxyvitamin D Alone Improves Skeletal Growth, Microarchitecture, and Strength in a Murine Model of XLH, Despite Enhanced FGF23 Expression. J Bone Miner Res. 2016 May;31(5):929-39. doi: 10.1002/jbmr.2783. Epub 2016 Feb 2.
PMID: 26751835
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Eva Liu
investigator title: Assistant Professor of Medicine
mesh term: Rickets
mesh term: Familial Hypophosphatemic Rickets
mesh term: Rickets, Hypophosphatemic
mesh term: Hypophosphatemia
mesh term: Calcitriol
mesh term: Dihydroxycholecalciferols
sharing ipd: No