<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/NCT04469517</url>
  </required_header>
  <id_info>
    <org_study_id>HIF in HHT</org_study_id>
    <nct_id>NCT04469517</nct_id>
  </id_info>
  <brief_title>Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia</brief_title>
  <official_title>Influence of Hypoxic Induced Factors in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Essen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Essen</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>
      Patients with hereditary hemorrhagic telangiectasia (HHT) suffer from an inherited disorder&#xD;
      leading to systemic vascular malformations. Mutations in several genes of the transforming&#xD;
      growth factor (TGF)-β superfamily pathway influence angiogenesis in patients with HHT. The&#xD;
      genetic loss of ALK1 or ENG alone are not sufficient to induce AVMs; environmental insults&#xD;
      that could trigger angiogenesis (e.g. wounding) are also needed. In this study it will be&#xD;
      analyzed if hypoxic induced factors could have an influence on the disease HHT.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hereditary hemorrhagic telangiectasia (HHT) is characterized by systemic vascular&#xD;
      malformations leading to recurrent bleedings and shunt formation especially in the liver,&#xD;
      lungs and the brain. The underlying pathogenic HHT mechanism remains unclear. The wide&#xD;
      variability in age of onset and severity of symptoms amongst patients, even within the same&#xD;
      family, suggests several factors contribute to the complexity of this disease. Mutations in&#xD;
      several genes of the transforming growth factor (TGF)-β superfamily pathway influence&#xD;
      angiogenesis in patients with HHT. The genetic loss of ALK1 or ENG alone are not sufficient&#xD;
      to induce AVMs; environmental insults that could trigger angiogenesis (e.g. wounding) are&#xD;
      also needed. In this study it will be analyzed if hypoxic induced factors could have an&#xD;
      influence on the disease HHT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 10, 2020</start_date>
  <completion_date type="Anticipated">October 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>12 Months</target_duration>
  <primary_outcome>
    <measure>Differences in hypoxic induced factors</measure>
    <time_frame>12 months</time_frame>
    <description>Differences in hypoxic induced factors analyzed in blood samples from patients with HHT and healthy controls</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation of level of hypoxic induced factors and disease severity</measure>
    <time_frame>12 months</time_frame>
    <description>Correlation of level of hypoxic induced factors in patients' blood sample and their disease severity</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Hereditary Hemorrhagic Telangiectasia</condition>
  <arm_group>
    <arm_group_label>HHT</arm_group_label>
    <description>patients with HHT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <description>persons age- and sex matched who do not suffer from HHT nor their first or second degree relatives</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>hypoxic induced factors</intervention_name>
    <description>hypoxic induced factors analyzed in blood sample</description>
    <arm_group_label>HHT</arm_group_label>
    <arm_group_label>control</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood sample&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with diagnosed hereditary hemorrhagic telangiectasie (HHT)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosed HHT (genetic testing and/ or fulfill at least 3 Curacao Criteria)&#xD;
&#xD;
          -  older than 17 years&#xD;
&#xD;
          -  ability to consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  if inclusion Criteria are not met&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Freya Droege, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University hospital Essen Otorhinolaryngology, Hufelandstr. 55, 45147 Essen, Germany</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Freya Droege, MD</last_name>
    <phone>0049201 723</phone>
    <phone_ext>2481</phone_ext>
    <email>freya.droege@uk-essen.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anna Wrobeln, PhD</last_name>
    <phone>0049201 723</phone>
    <phone_ext>4646</phone_ext>
    <email>anna.wrobeln@uk-essen.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital Essen</name>
      <address>
        <city>Essen</city>
        <state>NRW</state>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Freya Droege, MD</last_name>
      <phone>0049201723</phone>
      <phone_ext>2481</phone_ext>
      <email>freya.droege@uk-essen.de</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <citation>Kjeldsen AD, Vase P, Green A. [Hereditary hemorrhagic telangiectasia. A population-based study on prevalence and mortality among Danish HHT patients]. Ugeskr Laeger. 2000 Jun 19;162(25):3597-601. Danish.</citation>
    <PMID>11016284</PMID>
  </reference>
  <reference>
    <citation>Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6;91(1):66-7. doi: 10.1002/(sici)1096-8628(20000306)91:13.0.co;2-p.</citation>
    <PMID>10751092</PMID>
  </reference>
  <reference>
    <citation>Sanchez-Elsner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C. Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression. J Biol Chem. 2001 Oct 19;276(42):38527-35. doi: 10.1074/jbc.M104536200. Epub 2001 Aug 2.</citation>
    <PMID>11486006</PMID>
  </reference>
  <reference>
    <citation>Park SO, Wankhede M, Lee YJ, Choi EJ, Fliess N, Choe SW, Oh SH, Walter G, Raizada MK, Sorg BS, Oh SP. Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia. J Clin Invest. 2009 Nov;119(11):3487-96. doi: 10.1172/JCI39482. Epub 2009 Oct 1.</citation>
    <PMID>19805914</PMID>
  </reference>
  <reference>
    <citation>Attisano L, Wrana JL. Smads as transcriptional co-modulators. Curr Opin Cell Biol. 2000 Apr;12(2):235-43. doi: 10.1016/s0955-0674(99)00081-2.</citation>
    <PMID>10712925</PMID>
  </reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 8, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>July 14, 2023</last_update_submitted>
  <last_update_submitted_qc>July 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Essen</investigator_affiliation>
    <investigator_full_name>Freya Droege</investigator_full_name>
    <investigator_title>Principle Investigator, Speaker of Westgerman HHT Center</investigator_title>
  </responsible_party>
  <keyword>hereditary hemorrhagic telangiectasia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Telangiectasis</mesh_term>
    <mesh_term>Telangiectasia, Hereditary Hemorrhagic</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/NCT04469517
org study id: HIF in HHT
nct id: NCT04469517
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with hereditary hemorrhagic telangiectasia (HHT) suffer from an inherited disorder
      leading to systemic vascular malformations. Mutations in several genes of the transforming
      growth factor (TGF)-β superfamily pathway influence angiogenesis in patients with HHT. The
      genetic loss of ALK1 or ENG alone are not sufficient to induce AVMs; environmental insults
      that could trigger angiogenesis (e.g. wounding) are also needed. In this study it will be
      analyzed if hypoxic induced factors could have an influence on the disease HHT.
Hereditary hemorrhagic telangiectasia (HHT) is characterized by systemic vascular
      malformations leading to recurrent bleedings and shunt formation especially in the liver,
      lungs and the brain. The underlying pathogenic HHT mechanism remains unclear. The wide
      variability in age of onset and severity of symptoms amongst patients, even within the same
      family, suggests several factors contribute to the complexity of this disease. Mutations in
      several genes of the transforming growth factor (TGF)-β superfamily pathway influence
      angiogenesis in patients with HHT. The genetic loss of ALK1 or ENG alone are not sufficient
      to induce AVMs; environmental insults that could trigger angiogenesis (e.g. wounding) are
      also needed. In this study it will be analyzed if hypoxic induced factors could have an
      influence on the disease HHT.
observational model: Case-Control
time perspective: Prospective
measure: Differences in hypoxic induced factors
time frame: 12 months
description: Differences in hypoxic induced factors analyzed in blood samples from patients with HHT and healthy controls
measure: Correlation of level of hypoxic induced factors and disease severity
time frame: 12 months
description: Correlation of level of hypoxic induced factors in patients' blood sample and their disease severity
arm group label: HHT
description: patients with HHT
arm group label: control
description: persons age- and sex matched who do not suffer from HHT nor their first or second degree relatives
intervention type: Other
intervention name: hypoxic induced factors
description: hypoxic induced factors analyzed in blood sample
arm group label: HHT
arm group label: control
Blood sample
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Freya Droege, MD
role: Principal Investigator
affiliation: University hospital Essen Otorhinolaryngology, Hufelandstr. 55, 45147 Essen, Germany
last name: Freya Droege, MD
phone: 0049201 723
phone ext: 2481
email: freya.droege@uk-essen.de
last name: Anna Wrobeln, PhD
phone: 0049201 723
phone ext: 4646
email: anna.wrobeln@uk-essen.de
facility: 
status: Recruiting
contact: 
country: Germany
citation: Kjeldsen AD, Vase P, Green A. [Hereditary hemorrhagic telangiectasia. A population-based study on prevalence and mortality among Danish HHT patients]. Ugeskr Laeger. 2000 Jun 19;162(25):3597-601. Danish.
PMID: 11016284
citation: Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6;91(1):66-7. doi: 10.1002/(sici)1096-8628(20000306)91:13.0.co;2-p.
PMID: 10751092
citation: Sanchez-Elsner T, Botella LM, Velasco B, Corbi A, Attisano L, Bernabeu C. Synergistic cooperation between hypoxia and transforming growth factor-beta pathways on human vascular endothelial growth factor gene expression. J Biol Chem. 2001 Oct 19;276(42):38527-35. doi: 10.1074/jbc.M104536200. Epub 2001 Aug 2.
PMID: 11486006
citation: Park SO, Wankhede M, Lee YJ, Choi EJ, Fliess N, Choe SW, Oh SH, Walter G, Raizada MK, Sorg BS, Oh SP. Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia. J Clin Invest. 2009 Nov;119(11):3487-96. doi: 10.1172/JCI39482. Epub 2009 Oct 1.
PMID: 19805914
citation: Attisano L, Wrana JL. Smads as transcriptional co-modulators. Curr Opin Cell Biol. 2000 Apr;12(2):235-43. doi: 10.1016/s0955-0674(99)00081-2.
PMID: 10712925
responsible party type: Principal Investigator
investigator affiliation: University Hospital, Essen
investigator full name: Freya Droege
investigator title: Principle Investigator, Speaker of Westgerman HHT Center
mesh term: Telangiectasis
mesh term: Telangiectasia, Hereditary Hemorrhagic
sharing ipd: No