<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/NCT04484766</url>
  </required_header>
  <id_info>
    <org_study_id>2019-1498</org_study_id>
    <nct_id>NCT04484766</nct_id>
  </id_info>
  <brief_title>Preeclampsia Associated Vascular Aging</brief_title>
  <acronym>PAVA</acronym>
  <official_title>Preeclampsia Associated Vascular Age- Long-term Follow-up and New Prevention Strategy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jena University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jena University Hospital</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>
      To evaluate cardiovascular health, especially endothelial health, of women after&#xD;
      pre-eclampsia compared to women without pre-eclampsia, and to compare women who had taken&#xD;
      PETN during pregnancy with women who had not attempted treatment&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The clinical observation that women with pre-eclampsia have a high risk of early onset&#xD;
      cardiovascular disease with increased disease-associated mortality has led to the hypothesis&#xD;
      that the endothelial status of these women is characterized by early onset of aging. We want&#xD;
      to investigate the relationship between endothelial aging and pregnancy disorders such as&#xD;
      pre-eclampsia, which are dominated by endothelial dysfunction. Do endothelial changes precede&#xD;
      pregnancy and cause pre-eclampsia and later accelerated cardiovascular aging, or does&#xD;
      pre-eclampsia trigger premature endothelial aging in affected individuals for the first time?&#xD;
      The aim of this study is to investigate the cardiovascular health of women 10 to 20 years&#xD;
      after pre-eclampsia and to compare it with that of women with uneventful pregnancies. In&#xD;
      addition, the potential long-term endothelial protective effect of the NO-donor&#xD;
      pentaerithrityltetranitrate (PETN) is investigated.&#xD;
&#xD;
      This in vivo study will be extended in vitro by the analysis of senescence induction in&#xD;
      endothelial cells after pre-eclampsia associated stress. Additionally, the potential&#xD;
      protective effect of PETN on stress-induced senescence will be evaluated.&#xD;
&#xD;
      The ultimate goal is to establish a prospective long-term study on the effect of PETN on&#xD;
      vascular health in women with pre-eclampsia to assess whether treatment of endothelial&#xD;
      dysfunction during pregnancy could reduce endothelial aging and thus premature cardiovascular&#xD;
      morbidity and mortality in millions of women.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Anticipated">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">December 10, 2021</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>vascular health as combined outcome</measure>
    <time_frame>1 day 10-20 years after pregnancy</time_frame>
    <description>Comparison of the vascular health of patients after pre-eclampsia with that of women with complication-free pregnancies 10-20 years after pregnancy by assessing physical parameters (height, weight, Blood pressure, bioelectric impedance analysis), measuring cardiac output, transthoracic echocardiography, carotid intima media thickness, total vascular resistance, flow mediated dilation, critical flicker frequency, puls-wave velocity and augmentation index</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Potential long-term effect of PETN treatment using combined outcome of vascular health measurements in correlaation with treatment with PETN</measure>
    <time_frame>1 day 10-20 years after pregnancy</time_frame>
    <description>Analysis of a possible long-term effect of PETN treatment during pregnancy based on a vascular health comparison of patients who received PETN in the PETN pilot study from 2002 to 2008, or who received it in a personalised therapy trial, with those who received placebo or no therapy</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Endothelial cell senescence using senescence characterization of young and treated HUVEC cells</measure>
    <time_frame>1 day 10-20 years after pregnancy</time_frame>
    <description>In vitro analysis of endothelial cell senescence established by hosting group after pre-eclampsia induced stress effect, as well as the possible protective effect of PETN on endothelial cell aging</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Pre-Eclampsia</condition>
  <arm_group>
    <arm_group_label>Patient after pre-eclampsia</arm_group_label>
    <description>Patients with pre-eclampsia who were treated at the University Hospital of Jena between 1999-2009.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients after PETN treatment</arm_group_label>
    <description>Patients of the PETN pilot study, with PETN and patients who received PETN as an individual therapy trial</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Primary data collection</intervention_name>
    <description>Primary data collection takes place via questionnaires outside the study centre.&#xD;
All other investigations take place at the study centre:&#xD;
Physical examination: height, weight, BMI, blood pressure&#xD;
Cardiac examination: cardiac output&#xD;
Vascular measurements: Carotid intima media thickness, total peripheral resistance, blood pressure, flow-mediated vascular dilatation, critical flicker frequency, pulse wave velocity, augmentation index&#xD;
Serum analysis: basic laboratory, multiplex analysis (human vascular inflammation, human angiogenesis and adhesion molecule panel)</description>
    <arm_group_label>Patient after pre-eclampsia</arm_group_label>
    <arm_group_label>Patients after PETN treatment</arm_group_label>
    <other_name>Physical examination</other_name>
    <other_name>Cardiac measurement</other_name>
    <other_name>Vascular Measurement</other_name>
    <other_name>Serum analysis</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with pre-eclampsia 10 to 20 years ago. The patients are matched with the next&#xD;
        consenting patient who gave birth without pregnancy complications. Only singleton&#xD;
        pregnancies born between the 24th and 42nd week of pregnancy are considered.&#xD;
&#xD;
        Patients with and without PETN treatment are recruited from the patients who participated&#xD;
        in the PETN pilot study from 2002 to 2008. In addition, patients are recruited who received&#xD;
        PETN treatment as a personalised therapy trial. These are matched by patients without&#xD;
        treatment. The matching includes the indication for treatment, the week of pregnancy at&#xD;
        diagnosis and the percentiles of fetal growth&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants of the PETN pilot study from 2002-2008&#xD;
&#xD;
          -  controls: uneventful pregnancies from 2002-2008&#xD;
&#xD;
          -  Patients with pre-eclampsia with PETN treatment 10-20 years ago&#xD;
&#xD;
          -  Controls: patients with pre-eclampsia without PETN treatment 10-20 years ago&#xD;
&#xD;
          -  Written Informed Consent&#xD;
&#xD;
          -  Singleton pregnancy&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Patients who refuse to participate in the study&#xD;
&#xD;
          -  Impossibility of the outpatient presentation&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna Multhaup, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Klinik für Geburtsmedizin</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitätsklinikum Jena</name>
      <address>
        <city>Jena</city>
        <state>Thüringen</state>
        <zip>07747</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>April 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 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>Pre-Eclampsia</mesh_term>
    <mesh_term>Eclampsia</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/NCT04484766
org study id: 2019-1498
nct id: NCT04484766
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate cardiovascular health, especially endothelial health, of women after
      pre-eclampsia compared to women without pre-eclampsia, and to compare women who had taken
      PETN during pregnancy with women who had not attempted treatment
The clinical observation that women with pre-eclampsia have a high risk of early onset
      cardiovascular disease with increased disease-associated mortality has led to the hypothesis
      that the endothelial status of these women is characterized by early onset of aging. We want
      to investigate the relationship between endothelial aging and pregnancy disorders such as
      pre-eclampsia, which are dominated by endothelial dysfunction. Do endothelial changes precede
      pregnancy and cause pre-eclampsia and later accelerated cardiovascular aging, or does
      pre-eclampsia trigger premature endothelial aging in affected individuals for the first time?
      The aim of this study is to investigate the cardiovascular health of women 10 to 20 years
      after pre-eclampsia and to compare it with that of women with uneventful pregnancies. In
      addition, the potential long-term endothelial protective effect of the NO-donor
      pentaerithrityltetranitrate (PETN) is investigated.

      This in vivo study will be extended in vitro by the analysis of senescence induction in
      endothelial cells after pre-eclampsia associated stress. Additionally, the potential
      protective effect of PETN on stress-induced senescence will be evaluated.

      The ultimate goal is to establish a prospective long-term study on the effect of PETN on
      vascular health in women with pre-eclampsia to assess whether treatment of endothelial
      dysfunction during pregnancy could reduce endothelial aging and thus premature cardiovascular
      morbidity and mortality in millions of women.
observational model: Cohort
time perspective: Prospective
measure: vascular health as combined outcome
time frame: 1 day 10-20 years after pregnancy
description: Comparison of the vascular health of patients after pre-eclampsia with that of women with complication-free pregnancies 10-20 years after pregnancy by assessing physical parameters (height, weight, Blood pressure, bioelectric impedance analysis), measuring cardiac output, transthoracic echocardiography, carotid intima media thickness, total vascular resistance, flow mediated dilation, critical flicker frequency, puls-wave velocity and augmentation index
measure: Potential long-term effect of PETN treatment using combined outcome of vascular health measurements in correlaation with treatment with PETN
time frame: 1 day 10-20 years after pregnancy
description: Analysis of a possible long-term effect of PETN treatment during pregnancy based on a vascular health comparison of patients who received PETN in the PETN pilot study from 2002 to 2008, or who received it in a personalised therapy trial, with those who received placebo or no therapy
measure: Endothelial cell senescence using senescence characterization of young and treated HUVEC cells
time frame: 1 day 10-20 years after pregnancy
description: In vitro analysis of endothelial cell senescence established by hosting group after pre-eclampsia induced stress effect, as well as the possible protective effect of PETN on endothelial cell aging
arm group label: Patient after pre-eclampsia
description: Patients with pre-eclampsia who were treated at the University Hospital of Jena between 1999-2009.
arm group label: Patients after PETN treatment
description: Patients of the PETN pilot study, with PETN and patients who received PETN as an individual therapy trial
intervention type: Other
intervention name: Primary data collection
description: Primary data collection takes place via questionnaires outside the study centre.
All other investigations take place at the study centre:
Physical examination: height, weight, BMI, blood pressure
Cardiac examination: cardiac output
Vascular measurements: Carotid intima media thickness, total peripheral resistance, blood pressure, flow-mediated vascular dilatation, critical flicker frequency, pulse wave velocity, augmentation index
Serum analysis: basic laboratory, multiplex analysis (human vascular inflammation, human angiogenesis and adhesion molecule panel)
arm group label: Patient after pre-eclampsia
arm group label: Patients after PETN treatment
other name: Physical examination
other name: Cardiac measurement
other name: Vascular Measurement
other name: Serum analysis
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anna Multhaup, Dr. med.
role: Principal Investigator
affiliation: Klinik für Geburtsmedizin
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Pre-Eclampsia
mesh term: Eclampsia
sharing ipd: No