<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/NCT03758534</url>
  </required_header>
  <id_info>
    <org_study_id>GACI Natural History</org_study_id>
    <nct_id>NCT03758534</nct_id>
  </id_info>
  <brief_title>Natural History of GACI With or Without ARHR2 or PXE</brief_title>
  <official_title>The Natural History of Generalized Arterial Calcification of Infancy (GACI) With or Without Autosomal Recessive Hypophosphatemic Rickets Type 2 (ARHR2) or Pseudoxanthoma Elasticum (PXE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Westfälische Wilhelms-Universität Münster</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ICON plc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Westfälische Wilhelms-Universität Münster</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>
      Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder with an&#xD;
      estimated birth prevalence of around 1 in 400,000.1 GACI is generally fatal before birth or&#xD;
      within the first six months after birth. The cause of death is frequently myocardial&#xD;
      infarction or stroke. GACI is strongly associated with inactivating mutations in&#xD;
      ectonucleotide pyrophosphate/ phosphodiesterase 1 (ENPP1). Many patients with GACI, including&#xD;
      some without an ENPP1 mutation also present with mutations in adenosine triphosphate binding&#xD;
      cassette transporter protein subfamily C member 6 (ABCC6). Autosomal recessive&#xD;
      hypophosphatemic rickets type 2 (ARHR2) and pseudoxanthoma elasticum (PXE) are believed to be&#xD;
      closely related to GACI. ARHR2 is caused by mutations in the ENPP1 gene and PXE is caused by&#xD;
      mutations in the ABCC6 gene, with both being observed among patients with GACI. The natural&#xD;
      history of GACI and in particular its long term morbidity and mortality are poorly&#xD;
      understood. The primary objective of this study is to characterize overall survival among&#xD;
      patients with GACI, over time from birth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder with an&#xD;
      estimated birth prevalence of around 1 in 400,000.1 GACI is characterized by extensive&#xD;
      arterial calcifications, arterial stenosis, myointimal proliferation and periarticular&#xD;
      calcifications. Individuals with GACI also experience calcification in other body areas, such&#xD;
      as joints and organs. GACI is generally fatal before birth or within the first six months&#xD;
      after birth. The cause of death is frequently myocardial infarction or stroke. GACI is&#xD;
      strongly associated with inactivating mutations in ectonucleotide pyrophosphate/&#xD;
      phosphodiesterase 1 (ENPP1); around three quarters of GACI cases investigated had one or&#xD;
      several ENPP1 mutations. Many patients with GACI, including some without an ENPP1 mutation&#xD;
      also present with mutations in adenosine triphosphate binding cassette transporter protein&#xD;
      subfamily C member 6 (ABCC6). Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and&#xD;
      pseudoxanthoma elasticum (PXE) are believed to be closely related to GACI. ARHR2 is caused by&#xD;
      mutations in the ENPP1 gene5 and PXE is caused by mutations in the ABCC6 gene,3 with both&#xD;
      being observed among patients with GACI. The natural history of GACI and in particular its&#xD;
      long term morbidity and mortality are poorly understood, but a strong understanding of the&#xD;
      condition will be crucial for further therapy development and drug testing. This study aims&#xD;
      to address this knowledge gap.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      The primary objective of this study is to characterize overall survival among patients with&#xD;
      GACI, over time from birth.&#xD;
&#xD;
      Secondary objectives are to:&#xD;
&#xD;
        -  Characterize the patient and disease characteristics;&#xD;
&#xD;
        -  Describe symptomology at diagnosis and the change in symptomology over time;&#xD;
&#xD;
        -  Describe treatment patterns specific to GACI or rickets&#xD;
&#xD;
        -  Characterize mental/physical impairment, education, and employment situation;&#xD;
&#xD;
        -  Characterize the sequelae of the disease;&#xD;
&#xD;
        -  Prevalence of rickets; and&#xD;
&#xD;
        -  Growth velocities.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
        -  GACI genotype (mutation in ENPP1 and/or ABCC6) confirmed through mutational analysis of&#xD;
           the patient and a GACI phenotype confirmed by imaging or biopsy; or&#xD;
&#xD;
        -  GACI phenotype confirmed with imaging, biopsy, or mutational analysis of the parents&#xD;
           indicating a GACI genotype (mutation in ENPP1 and/or ABCC6) coinciding with symptoms of&#xD;
           the patient.&#xD;
&#xD;
      Data will be collected for both living and deceased patients&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Retrospective multicenter chart review&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 15, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>Recruitment for this study will end in March 2019</time_frame>
    <description>This study will record the survival rate in patients with GACI</description>
  </primary_outcome>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Generalized Arterial Calcification in Infancy</condition>
  <condition>Autosomal Recessive Hypophosphatemic Rickets</condition>
  <condition>Pseudoxanthoma Elasticum</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No intervention</intervention_name>
    <description>This is a retrospective chart review study.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Probands with proven history of generalized arterial calcification of infancy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  GACI genotype (mutation in ENPP1 and/or ABCC6) confirmed through mutational analysis&#xD;
             of the patient and a GACI phenotype confirmed by imaging or biopsy; or&#xD;
&#xD;
          -  GACI phenotype confirmed with imaging, biopsy, or mutational analysis of the parents&#xD;
             indicating a GACI genotype (mutation in ENPP1 and/or ABCC6) coinciding with symptoms&#xD;
             of the patient.&#xD;
&#xD;
          -  Data will be collected for both living and deceased patients&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Caregivers are not able to give written consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Frank Rutsch, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>WWU Munster</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Frank Rutsch, MD</last_name>
    <phone>+49251-8347700</phone>
    <email>frank.rutsch@ukmuenster.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kerstin Mueller, PhD</last_name>
    <phone>+16042352172</phone>
    <email>kerstin.mueller@iconplc.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>WWU Munster</name>
      <address>
        <city>Münster</city>
        <zip>48149</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frank Rutsch, MD</last_name>
      <phone>+492518347700</phone>
      <email>frank.rutsch@ukmuenster.de</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>November 28, 2018</last_update_submitted>
  <last_update_submitted_qc>November 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Westfälische Wilhelms-Universität Münster</investigator_affiliation>
    <investigator_full_name>Frank Rutsch</investigator_full_name>
    <investigator_title>Prof. Dr. Frank Rutsch, MD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rickets</mesh_term>
    <mesh_term>Rickets, Hypophosphatemic</mesh_term>
    <mesh_term>Familial Hypophosphatemic Rickets</mesh_term>
    <mesh_term>Pseudoxanthoma Elasticum</mesh_term>
    <mesh_term>Arteriosclerosis</mesh_term>
    <mesh_term>Calcinosis</mesh_term>
  </condition_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/NCT03758534
org study id: GACI Natural History
nct id: NCT03758534
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder with an
      estimated birth prevalence of around 1 in 400,000.1 GACI is generally fatal before birth or
      within the first six months after birth. The cause of death is frequently myocardial
      infarction or stroke. GACI is strongly associated with inactivating mutations in
      ectonucleotide pyrophosphate/ phosphodiesterase 1 (ENPP1). Many patients with GACI, including
      some without an ENPP1 mutation also present with mutations in adenosine triphosphate binding
      cassette transporter protein subfamily C member 6 (ABCC6). Autosomal recessive
      hypophosphatemic rickets type 2 (ARHR2) and pseudoxanthoma elasticum (PXE) are believed to be
      closely related to GACI. ARHR2 is caused by mutations in the ENPP1 gene and PXE is caused by
      mutations in the ABCC6 gene, with both being observed among patients with GACI. The natural
      history of GACI and in particular its long term morbidity and mortality are poorly
      understood. The primary objective of this study is to characterize overall survival among
      patients with GACI, over time from birth.
Background:

      Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder with an
      estimated birth prevalence of around 1 in 400,000.1 GACI is characterized by extensive
      arterial calcifications, arterial stenosis, myointimal proliferation and periarticular
      calcifications. Individuals with GACI also experience calcification in other body areas, such
      as joints and organs. GACI is generally fatal before birth or within the first six months
      after birth. The cause of death is frequently myocardial infarction or stroke. GACI is
      strongly associated with inactivating mutations in ectonucleotide pyrophosphate/
      phosphodiesterase 1 (ENPP1); around three quarters of GACI cases investigated had one or
      several ENPP1 mutations. Many patients with GACI, including some without an ENPP1 mutation
      also present with mutations in adenosine triphosphate binding cassette transporter protein
      subfamily C member 6 (ABCC6). Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and
      pseudoxanthoma elasticum (PXE) are believed to be closely related to GACI. ARHR2 is caused by
      mutations in the ENPP1 gene5 and PXE is caused by mutations in the ABCC6 gene,3 with both
      being observed among patients with GACI. The natural history of GACI and in particular its
      long term morbidity and mortality are poorly understood, but a strong understanding of the
      condition will be crucial for further therapy development and drug testing. This study aims
      to address this knowledge gap.

      Objectives:

      The primary objective of this study is to characterize overall survival among patients with
      GACI, over time from birth.

      Secondary objectives are to:

        -  Characterize the patient and disease characteristics;

        -  Describe symptomology at diagnosis and the change in symptomology over time;

        -  Describe treatment patterns specific to GACI or rickets

        -  Characterize mental/physical impairment, education, and employment situation;

        -  Characterize the sequelae of the disease;

        -  Prevalence of rickets; and

        -  Growth velocities.

      Eligibility:

        -  GACI genotype (mutation in ENPP1 and/or ABCC6) confirmed through mutational analysis of
           the patient and a GACI phenotype confirmed by imaging or biopsy; or

        -  GACI phenotype confirmed with imaging, biopsy, or mutational analysis of the parents
           indicating a GACI genotype (mutation in ENPP1 and/or ABCC6) coinciding with symptoms of
           the patient.

      Data will be collected for both living and deceased patients

      Design:

      Retrospective multicenter chart review
observational model: Cohort
time perspective: Retrospective
measure: Survival
time frame: Recruitment for this study will end in March 2019
description: This study will record the survival rate in patients with GACI
intervention type: Other
intervention name: No intervention
description: This is a retrospective chart review study.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
last name: Frank Rutsch, MD
role: Principal Investigator
affiliation: WWU Munster
last name: Frank Rutsch, MD
phone: +49251-8347700
email: frank.rutsch@ukmuenster.de
last name: Kerstin Mueller, PhD
phone: +16042352172
email: kerstin.mueller@iconplc.com
facility: 
status: Recruiting
contact: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Westfälische Wilhelms-Universität Münster
investigator full name: Frank Rutsch
investigator title: Prof. Dr. Frank Rutsch, MD
mesh term: Rickets
mesh term: Rickets, Hypophosphatemic
mesh term: Familial Hypophosphatemic Rickets
mesh term: Pseudoxanthoma Elasticum
mesh term: Arteriosclerosis
mesh term: Calcinosis
sharing ipd: No