<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/NCT02237625</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00049204</org_study_id>
    <secondary_id>Pro00049204</secondary_id>
    <nct_id>NCT02237625</nct_id>
  </id_info>
  <brief_title>Natural History Study of Patients With Hypophosphatasia (HPP)</brief_title>
  <acronym>NatHisHPP</acronym>
  <official_title>Natural History Study of Adult and Pediatric Patients With Hypophosphatasia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by defective bone&#xD;
      and teeth mineralization caused by mutations of the ALPL gene, which encodes for the&#xD;
      tissue-nonspecific alkaline phosphatase (TNSALP) isozyme, resulting in decreased serum and&#xD;
      bone alkaline phosphatase levels. To date, over 250 different mutations in the gene encoding&#xD;
      TNSALP have been associated with HPP. Clinically, the loss of TNSALP function results in&#xD;
      progressive skeletal impact as well as progressive impact on all other major organ systems.&#xD;
      It clinically manifests as rickets in infants and children and osteomalacia at all ages. The&#xD;
      severe form of the disease has been estimated to have a prevalence of about 1 in every&#xD;
      100,000 live births.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a&#xD;
      wide range of clinical expressivity, with a spectrum ranging from stillbirth without&#xD;
      mineralized bone to early loss of teeth without bone symptoms. Depending on the age at&#xD;
      diagnosis six clinical forms are currently recognized: perinatal (lethal), perinatal benign,&#xD;
      infantile, childhood, adult and odontohypophosphatasia. Severe forms of HPP (perinatal and&#xD;
      infantile) are inherited as an autosomal recessive trait and in milder forms (adult and&#xD;
      odontohypophosphatasia) autosomal recessive and autosomal dominant inheritance coexist.&#xD;
&#xD;
      Because of the rarity of HPP as well as the side spectrum of both clinical presentation and&#xD;
      inheritance patterns of the HPP trait, a natural history study cataloging specific clinical&#xD;
      data with HPP would prove invaluable for future research into this disease. Specifically, it&#xD;
      is our goal to create a comprehensive multi-discipline modality for care for hypophosphatasia&#xD;
      patients, researching clinical manifestations of the disease such as extent of bone disease,&#xD;
      ophthalmologic manifestations, orthopedic issues, renal issues, musculoskeletal&#xD;
      manifestations as well as other more anecdotal findings such as those seen with cochlear&#xD;
      implant failures and/or early menopause.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">September 2026</completion_date>
  <primary_completion_date type="Anticipated">September 2024</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Family-Based</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>100 Years</target_duration>
  <primary_outcome>
    <measure>Medical History of HPP Patients</measure>
    <time_frame>100 years</time_frame>
    <description>Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>long-term efficacy of treatment modalities</measure>
    <time_frame>100 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>potential long term complications of the disease and/or treatment</measure>
    <time_frame>100 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life issues for patients living with hypophosphatasia</measure>
    <time_frame>100 years</time_frame>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Hypophosphatasia</condition>
  <arm_group>
    <arm_group_label>Medical History of HPP Patients</arm_group_label>
    <description>Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Up to 100 minor and 100 adult subjects will be enrolled into this natural history study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients or their legal representative must provide written informed consent or, if&#xD;
             applicable, qualify for waiver of consent.&#xD;
&#xD;
          -  Patients must have a pre-established clinical diagnosis of HPP, as indicated by one or&#xD;
             more of the following:&#xD;
&#xD;
               -  Serum alkaline phosphatase (ALP) below the age-adjusted normal range&#xD;
&#xD;
               -  Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered&#xD;
                  for at least 1 week prior to determination)&#xD;
&#xD;
               -  Evidence of osteopenia or osteomalacia on skeletal radiographs&#xD;
&#xD;
               -  Genetic analysis fof the ALPL gene&#xD;
&#xD;
          -  Must be current patient in the Duke University System.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any patient without confirmation of clinical diagnosis of HPP.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Priya Kishnani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Janet G Blount, BA</last_name>
    <phone>919-681-7962</phone>
    <email>janet.blount@duke.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Priya Kishnani, MD</last_name>
      <phone>919-681-1939</phone>
      <email>kishn001@mc.duke.edu</email>
    </contact>
    <contact_backup>
      <last_name>Stephanie DeArmey, PA-C</last_name>
      <phone>(919) 681-1946</phone>
      <email>dearm001@mc.duke.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>March 6, 2023</last_update_submitted>
  <last_update_submitted_qc>March 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypophosphatasia</keyword>
  <keyword>HPP</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypophosphatasia</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/NCT02237625
org study id: Pro00049204
secondary id: Pro00049204
nct id: NCT02237625
lead sponsor: 
has dmc: Yes
Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by defective bone
      and teeth mineralization caused by mutations of the ALPL gene, which encodes for the
      tissue-nonspecific alkaline phosphatase (TNSALP) isozyme, resulting in decreased serum and
      bone alkaline phosphatase levels. To date, over 250 different mutations in the gene encoding
      TNSALP have been associated with HPP. Clinically, the loss of TNSALP function results in
      progressive skeletal impact as well as progressive impact on all other major organ systems.
      It clinically manifests as rickets in infants and children and osteomalacia at all ages. The
      severe form of the disease has been estimated to have a prevalence of about 1 in every
      100,000 live births.
Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a
      wide range of clinical expressivity, with a spectrum ranging from stillbirth without
      mineralized bone to early loss of teeth without bone symptoms. Depending on the age at
      diagnosis six clinical forms are currently recognized: perinatal (lethal), perinatal benign,
      infantile, childhood, adult and odontohypophosphatasia. Severe forms of HPP (perinatal and
      infantile) are inherited as an autosomal recessive trait and in milder forms (adult and
      odontohypophosphatasia) autosomal recessive and autosomal dominant inheritance coexist.

      Because of the rarity of HPP as well as the side spectrum of both clinical presentation and
      inheritance patterns of the HPP trait, a natural history study cataloging specific clinical
      data with HPP would prove invaluable for future research into this disease. Specifically, it
      is our goal to create a comprehensive multi-discipline modality for care for hypophosphatasia
      patients, researching clinical manifestations of the disease such as extent of bone disease,
      ophthalmologic manifestations, orthopedic issues, renal issues, musculoskeletal
      manifestations as well as other more anecdotal findings such as those seen with cochlear
      implant failures and/or early menopause.
observational model: Family-Based
time perspective: Prospective
measure: Medical History of HPP Patients
time frame: 100 years
description: Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP
measure: long-term efficacy of treatment modalities
time frame: 100 years
measure: potential long term complications of the disease and/or treatment
time frame: 100 years
measure: quality of life issues for patients living with hypophosphatasia
time frame: 100 years
arm group label: Medical History of HPP Patients
description: Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Priya Kishnani, MD
role: Principal Investigator
affiliation: Duke University
last name: Janet G Blount, BA
phone: 919-681-7962
email: janet.blount@duke.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Hypophosphatasia