<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/NCT03813550</url>
  </required_header>
  <id_info>
    <org_study_id>2018/79</org_study_id>
    <nct_id>NCT03813550</nct_id>
  </id_info>
  <brief_title>Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)</brief_title>
  <acronym>IMPROVE</acronym>
  <official_title>Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Angers</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Maastricht University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Biofortis Mérieux NutriSciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Angers</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>
      This study aims to demonstrate a potential association between gut microbiota composition,&#xD;
      plasma levels of various forms of vitamin K, and severity of clinical manifestations of&#xD;
      Pseudoxanthoma Elasticum (PXE).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Vitamin K deficiency contributes to pathological calcification which underlies the clinical&#xD;
      picture of pseudoxanthoma elasticum (PXE), an inherited autosomal recessive disease. A&#xD;
      substantial proportion of vitamin K, namely the K2 form (menaquinones), is produced by gut&#xD;
      microbiota. In healthy volunteers fecal levels of the major menaquinone producers,&#xD;
      Escherichia coli and Bacteroides species, are approximately 5 and 9 log10 CFU/g dry weight&#xD;
      respectively. There is however a lack of data on gut microbiota in PXE patients. The&#xD;
      objective of our project is to demonstrate a potential association between gut microbiota&#xD;
      composition, plasma levels of various forms of vitamin K and severity of clinical&#xD;
      manifestations in PXE patients.&#xD;
&#xD;
      This study will be performed as Research surrounding bio collection &quot;Clinical and biological&#xD;
      exploration of PXE patients&quot; kept at the Center of Biological Resources of Angers University&#xD;
      Hospital (bio collection n° DC 20116-14-67, authorization to transfer n° 2016-27-99). Fecal&#xD;
      samples, plasma samples and clinical data will be collected from patients diagnosed with PXE&#xD;
      who will be monitored at the Angers University Hospital Referral Center (France) in&#xD;
      2019-2020. Clinical severity of PXE will be assessed using modified Phenodex score. Gut&#xD;
      microbiota will be analyzed using metagenomic sequencing. Plasma Vitamin K species and fecal&#xD;
      excretion of menaquinones will be assessed using HPLC. Plasma dp-ucMGP (circulating biomarker&#xD;
      of vitamin K status) and serum PIVKA-II (protein induced by vitamin K absence-II) will be&#xD;
      assessed using immunoassay. Results will be compared to healthy age- and gender-matched&#xD;
      controls from the pre-existing Biofortis database.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 21, 2019</start_date>
  <completion_date type="Anticipated">January 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">January 30, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fecal samples for intestinal microbiota analysis</measure>
    <time_frame>15 min</time_frame>
    <description>Gut microbiota composition and relative abundance of species (via metagenomic sequencing)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fecal samples for assessment of various forms of vitamin K</measure>
    <time_frame>15 min</time_frame>
    <description>Fecal Vitamin K species</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood samples for assessment of various forms of vitamin K</measure>
    <time_frame>15 min</time_frame>
    <description>Plasma Vitamin K species</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood samples for assessment of dp-ucMGP</measure>
    <time_frame>15 min</time_frame>
    <description>Plasma dp-ucMGP</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood samples for assessment of PIVKA-II</measure>
    <time_frame>15 min</time_frame>
    <description>Serum PIVKA-II</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes</measure>
    <time_frame>15 min</time_frame>
    <description>Modified Phenodex score:&#xD;
Skin lesions severity: S0=No sign; S1= Papules/bumps; S2= Plaques of coalesced papules; S3= Lax and redundant skin&#xD;
Number of affected skin sites: for Typical and Nontypical areas&#xD;
Ophthalmological involvement: E0= No sign; E1= Peau d'orange ; E2= Angioid streaks; E3a=Medical history of bleeding and/or scarring; E3b= Unilateral or bilateral blindness&#xD;
Gastrointestinal bleeding: G0= No sign; G1= Gastrointestinal bleeding as related to PXE&#xD;
Vascular involvement: V0= No sign; V1= Weak or absent pulse or peripheral artery disease revealed by vascular imaging; V2= Intermittent claudication; V3= Medical history of vascular surgery or Stroke/TIA&#xD;
Cardiac involvement: C0= No sign; C1= medical history of chest pain/angina/abnormal EKG or abnormal stress test with no symptom, or Mitral insufficiency; C2= Heart attack&#xD;
Renal involvement: R0= No sign; R1a= asymptomatic nephrocalcinosis revealed by imaging; R1b= Nephrolithiasis</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Pseudoxanthoma Elasticum</condition>
  <arm_group>
    <arm_group_label>PXE cohort 2019-2020</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>PXE patient cohort monitored at referral centre from 2019 to 2020: fecal and blood samples</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Fecal and blood samples</intervention_name>
    <description>Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K</description>
    <arm_group_label>PXE cohort 2019-2020</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with phenotypically and genetically (ABCC6) proven PXE&#xD;
&#xD;
          -  Aged over 18 years&#xD;
&#xD;
          -  Written consent obtained for Angers University Hospital (France) PXE bio-collection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients under the age of 18&#xD;
&#xD;
          -  Patients unwilling to participate in the study, or unable to sign the bio-collection&#xD;
             consent form&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ludovic MARTIN, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Dermatology, University Hospital of Angers</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ludovic MARTIN, MD, PhD</last_name>
    <phone>+332.41.35.55.76</phone>
    <email>LuMartin@chu-angers.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Biofortis Mérieux NutriSciences</name>
      <address>
        <city>Saint-Herblain</city>
        <state>Pays De La Loire</state>
        <zip>44800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Department of Dermatology, University Hospital of Angers</name>
      <address>
        <city>Angers</city>
        <state>Pays De Loire</state>
        <zip>49933</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ludovic Martin, MD, PhD</last_name>
      <phone>+332.41.35.55.76</phone>
      <email>LuMartin@chu-angers.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Department of Biochemistry, University Maastricht</name>
      <address>
        <city>Maastricht</city>
        <zip>6229</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>France</country>
    <country>Netherlands</country>
  </location_countries>
  <reference>
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  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 19, 2019</study_first_submitted>
  <study_first_submitted_qc>January 19, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>January 31, 2019</last_update_submitted>
  <last_update_submitted_qc>January 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>PXE</keyword>
  <keyword>calcification</keyword>
  <keyword>Gla proteins</keyword>
  <keyword>gut microbiota</keyword>
  <keyword>vitamin K2</keyword>
  <keyword>menaquinones</keyword>
  <keyword>taxonomic meta-sequencing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pseudoxanthoma Elasticum</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03813550
org study id: 2018/79
nct id: NCT03813550
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to demonstrate a potential association between gut microbiota composition,
      plasma levels of various forms of vitamin K, and severity of clinical manifestations of
      Pseudoxanthoma Elasticum (PXE).
Vitamin K deficiency contributes to pathological calcification which underlies the clinical
      picture of pseudoxanthoma elasticum (PXE), an inherited autosomal recessive disease. A
      substantial proportion of vitamin K, namely the K2 form (menaquinones), is produced by gut
      microbiota. In healthy volunteers fecal levels of the major menaquinone producers,
      Escherichia coli and Bacteroides species, are approximately 5 and 9 log10 CFU/g dry weight
      respectively. There is however a lack of data on gut microbiota in PXE patients. The
      objective of our project is to demonstrate a potential association between gut microbiota
      composition, plasma levels of various forms of vitamin K and severity of clinical
      manifestations in PXE patients.

      This study will be performed as Research surrounding bio collection "Clinical and biological
      exploration of PXE patients" kept at the Center of Biological Resources of Angers University
      Hospital (bio collection n° DC 20116-14-67, authorization to transfer n° 2016-27-99). Fecal
      samples, plasma samples and clinical data will be collected from patients diagnosed with PXE
      who will be monitored at the Angers University Hospital Referral Center (France) in
      2019-2020. Clinical severity of PXE will be assessed using modified Phenodex score. Gut
      microbiota will be analyzed using metagenomic sequencing. Plasma Vitamin K species and fecal
      excretion of menaquinones will be assessed using HPLC. Plasma dp-ucMGP (circulating biomarker
      of vitamin K status) and serum PIVKA-II (protein induced by vitamin K absence-II) will be
      assessed using immunoassay. Results will be compared to healthy age- and gender-matched
      controls from the pre-existing Biofortis database.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Fecal samples for intestinal microbiota analysis
time frame: 15 min
description: Gut microbiota composition and relative abundance of species (via metagenomic sequencing)
measure: Fecal samples for assessment of various forms of vitamin K
time frame: 15 min
description: Fecal Vitamin K species
measure: Blood samples for assessment of various forms of vitamin K
time frame: 15 min
description: Plasma Vitamin K species
measure: Blood samples for assessment of dp-ucMGP
time frame: 15 min
description: Plasma dp-ucMGP
measure: Blood samples for assessment of PIVKA-II
time frame: 15 min
description: Serum PIVKA-II
measure: Severity of ocular and cardiovascular PXE manifestations and extent of PXE skin changes
time frame: 15 min
description: Modified Phenodex score:
Skin lesions severity: S0=No sign; S1= Papules/bumps; S2= Plaques of coalesced papules; S3= Lax and redundant skin
Number of affected skin sites: for Typical and Nontypical areas
Ophthalmological involvement: E0= No sign; E1= Peau d'orange ; E2= Angioid streaks; E3a=Medical history of bleeding and/or scarring; E3b= Unilateral or bilateral blindness
Gastrointestinal bleeding: G0= No sign; G1= Gastrointestinal bleeding as related to PXE
Vascular involvement: V0= No sign; V1= Weak or absent pulse or peripheral artery disease revealed by vascular imaging; V2= Intermittent claudication; V3= Medical history of vascular surgery or Stroke/TIA
Cardiac involvement: C0= No sign; C1= medical history of chest pain/angina/abnormal EKG or abnormal stress test with no symptom, or Mitral insufficiency; C2= Heart attack
Renal involvement: R0= No sign; R1a= asymptomatic nephrocalcinosis revealed by imaging; R1b= Nephrolithiasis
arm group label: PXE cohort 2019-2020
arm group type: Other
description: PXE patient cohort monitored at referral centre from 2019 to 2020: fecal and blood samples
intervention type: Diagnostic Test
intervention name: Fecal and blood samples
description: Fecal samples for intestinal microbiota analysis; Blood and fecal samples for assessment of various forms of vitamin K
arm group label: PXE cohort 2019-2020
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ludovic MARTIN, MD, PhD
role: Principal Investigator
affiliation: Department of Dermatology, University Hospital of Angers
last name: Ludovic MARTIN, MD, PhD
phone: +332.41.35.55.76
email: LuMartin@chu-angers.fr
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
country: France
country: Netherlands
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responsible party type: Sponsor
mesh term: Pseudoxanthoma Elasticum
sharing ipd: Undecided