<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/NCT03771105</url>
  </required_header>
  <id_info>
    <org_study_id>2000023461</org_study_id>
    <secondary_id>1UL1TR001863-01</secondary_id>
    <nct_id>NCT03771105</nct_id>
  </id_info>
  <brief_title>The Impact of Phosphate Metabolism on Healthy Aging</brief_title>
  <official_title>The Impact of Phosphate Metabolism on Healthy Aging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center for Advancing Translational Sciences (NCATS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Determine the association between duration and dose of chronic conventional therapy with Pi&#xD;
      and renal (nephrocalcinosis/nephrolithiasis), vascular (endothelial function), and&#xD;
      cardiovascular function (echo- cardiography) in patients with hereditary hypophosphatemic&#xD;
      rickets with hypercalciuria (HHRH) and patients with X-linked hypophosphatemia (XLH).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The central hypothesis of this proposal is that patients with X-linked hypophosphatemia&#xD;
      (XLH), when matched for duration and dose of phosphate (Pi) therapy to patients with&#xD;
      hereditary hypophosphatemic rickets with hypercalciuria (HHRH), will evidence greater&#xD;
      cardiovascular and vascular debility than patients with HHRH. The overall objectives of this&#xD;
      project are to utilize our existing longitudinal databases for individuals with XLH and HHRH&#xD;
      through an interdisciplinary collaboration between pediatric and adult endocrinology to: i)&#xD;
      quantify the impact of exposure to Pi therapy across the lifespan on cardiovascular and renal&#xD;
      complications, which are key aging endpoints, ii) determine the acute response to Pi loading&#xD;
      in XLH and HHRH by studying the changes in surrogate markers of cardiovascular and renal&#xD;
      function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Anticipated">November 2023</completion_date>
  <primary_completion_date type="Anticipated">November 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>crossover parallel</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Parathyroid Hormone (PTH) levels</measure>
    <time_frame>30 days</time_frame>
    <description>PTH levels are expected to increase over baseline after phosphate supplement (Pi).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fibroblast Growth Factor 23 (FGF23) levels</measure>
    <time_frame>30 days</time_frame>
    <description>FGF23 levels are expected to increase over baseline after phosphate supplement (Pi).</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Hypophosphatemia</condition>
  <condition>Rickets</condition>
  <condition>Hypercalciuria</condition>
  <condition>XLH</condition>
  <condition>HHRH</condition>
  <arm_group>
    <arm_group_label>Patients with hereditary hypophosphatemic rickets with HHRH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with X-linked Hypophosphatemia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients with X-linked hypophosphatemia</description>
  </arm_group>
  <arm_group>
    <arm_group_label>15 Patients with X-linked Hypophosphatemia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>15 Patients with X-linked Hypophosphatemia that will receive phosphate treatment for 30 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>15 Patients Hereditary hypophosphatemic rickets with HHRH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>15 patients withHereditary hypophosphatemic rickets with hypercalciuria (HHRH) that will receive phosphate treatment for 30 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>phosphate</intervention_name>
    <description>The target daily phosphate (Pi) intake is 3,500 mg/day (dietary intake plus our supplementation) for this study. Subjects will take a supplement of Pi (as KPhos Neutral 250 mg/tablet) to reach this target. Subjects will receive treatment for 30 days.</description>
    <arm_group_label>15 Patients Hereditary hypophosphatemic rickets with HHRH</arm_group_label>
    <arm_group_label>15 Patients with X-linked Hypophosphatemia</arm_group_label>
    <arm_group_label>Patients with X-linked Hypophosphatemia</arm_group_label>
    <arm_group_label>Patients with hereditary hypophosphatemic rickets with HHRH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children above the age of 13 years&#xD;
&#xD;
          -  Younger and older adults with XLH and HHRH with confirmed NPT2c mutations affecting&#xD;
             both copies of the NPT2c gene (HHRH) or one copy of the PHEX gene (XLH)&#xD;
&#xD;
          -  Be willing to provide access to prior medical records to determine eligibility&#xD;
             including imaging, biochemical, medical, and surgical history data&#xD;
&#xD;
          -  Be willing and able to complete all aspects of the study&#xD;
&#xD;
          -  Be willing to adhere to the study visit schedule and comply with the assessments (in&#xD;
             the opinion of the investigator).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects will be excluded, if they are children younger than age 13 years&#xD;
&#xD;
          -  Subjects that have other diseases likely to impact bone and mineral metabolism (e.g.&#xD;
             renal, hepatic, gastrointestinal disorders, and malignancy),&#xD;
&#xD;
          -  Subjects that are currently pregnant,&#xD;
&#xD;
          -  Subjects that received medical therapy or developed any condition, which in the&#xD;
             opinion of the investigator, could present a concern for either subject safety or&#xD;
             difficulty with data interpretation.&#xD;
&#xD;
          -  Subjects will be excluded from Aim 2, if they are unable to tolerate supplemental&#xD;
             phosphate.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clemens Bergwitz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>March 3, 2023</last_update_submitted>
  <last_update_submitted_qc>March 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 7, 2023</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>Rickets</mesh_term>
    <mesh_term>Hypophosphatemia</mesh_term>
    <mesh_term>Hypercalciuria</mesh_term>
  </condition_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/NCT03771105
org study id: 2000023461
secondary id: 1UL1TR001863-01
nct id: NCT03771105
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Determine the association between duration and dose of chronic conventional therapy with Pi
      and renal (nephrocalcinosis/nephrolithiasis), vascular (endothelial function), and
      cardiovascular function (echo- cardiography) in patients with hereditary hypophosphatemic
      rickets with hypercalciuria (HHRH) and patients with X-linked hypophosphatemia (XLH).
The central hypothesis of this proposal is that patients with X-linked hypophosphatemia
      (XLH), when matched for duration and dose of phosphate (Pi) therapy to patients with
      hereditary hypophosphatemic rickets with hypercalciuria (HHRH), will evidence greater
      cardiovascular and vascular debility than patients with HHRH. The overall objectives of this
      project are to utilize our existing longitudinal databases for individuals with XLH and HHRH
      through an interdisciplinary collaboration between pediatric and adult endocrinology to: i)
      quantify the impact of exposure to Pi therapy across the lifespan on cardiovascular and renal
      complications, which are key aging endpoints, ii) determine the acute response to Pi loading
      in XLH and HHRH by studying the changes in surrogate markers of cardiovascular and renal
      function.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: crossover parallel
measure: Parathyroid Hormone (PTH) levels
time frame: 30 days
description: PTH levels are expected to increase over baseline after phosphate supplement (Pi).
measure: Fibroblast Growth Factor 23 (FGF23) levels
time frame: 30 days
description: FGF23 levels are expected to increase over baseline after phosphate supplement (Pi).
arm group label: Patients with hereditary hypophosphatemic rickets with HHRH
arm group type: Experimental
description: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)
arm group label: Patients with X-linked Hypophosphatemia
arm group type: Active Comparator
description: Patients with X-linked hypophosphatemia
arm group label: 15 Patients with X-linked Hypophosphatemia
arm group type: Active Comparator
description: 15 Patients with X-linked Hypophosphatemia that will receive phosphate treatment for 30 days.
arm group label: 15 Patients Hereditary hypophosphatemic rickets with HHRH
arm group type: Active Comparator
description: 15 patients withHereditary hypophosphatemic rickets with hypercalciuria (HHRH) that will receive phosphate treatment for 30 days.
intervention type: Drug
intervention name: phosphate
description: The target daily phosphate (Pi) intake is 3,500 mg/day (dietary intake plus our supplementation) for this study. Subjects will take a supplement of Pi (as KPhos Neutral 250 mg/tablet) to reach this target. Subjects will receive treatment for 30 days.
arm group label: 15 Patients Hereditary hypophosphatemic rickets with HHRH
arm group label: 15 Patients with X-linked Hypophosphatemia
arm group label: Patients with X-linked Hypophosphatemia
arm group label: Patients with hereditary hypophosphatemic rickets with HHRH
criteria: 
gender: All
minimum age: 13 Years
maximum age: N/A
healthy volunteers: No
last name: Clemens Bergwitz, MD
role: Principal Investigator
affiliation: Yale University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rickets
mesh term: Hypophosphatemia
mesh term: Hypercalciuria