<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/NCT03806283</url>
  </required_header>
  <id_info>
    <org_study_id>Meriter IRB 2018-006</org_study_id>
    <secondary_id>5R01HL134779-02</secondary_id>
    <secondary_id>A532860</secondary_id>
    <secondary_id>SMPH/OBSTET &amp; GYNECOL/OBSTET</secondary_id>
    <secondary_id>Protocol Version 10/25/2022</secondary_id>
    <secondary_id>2018-1368</secondary_id>
    <nct_id>NCT03806283</nct_id>
  </id_info>
  <brief_title>Mechanisms of Pregnancy Vascular Adaptations</brief_title>
  <official_title>Angiotensin 2 Receptor (AT2R) Expression/Activation in Endothelial Cells in Preeclampsia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Wisconsin, Madison</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>
      The investigators will collect omental tissue (research surgical excision) and placental&#xD;
      tissue (standard of care clinical delivery) from both preeclamptic and non-preeclamptic women&#xD;
      during their c-section and use these samples to study the blood vessels, specifically the&#xD;
      expression/activation of the AT2R.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Trial Design: The study is a comparison of two cohorts, those with and without preeclampsia&#xD;
      during pregnancy. The team plans to investigate role of FABP4, PFAS and AT2 in modulation of&#xD;
      vascular function/dysfunction using vessels isolated from the omental biopsies. The&#xD;
      investigators will examine for the evidence of fetal vascular dysfunction mediated by&#xD;
      decreased expression of AT2 in preeclampsia using vessels isolated from the placentas.&#xD;
&#xD;
      Study Population: The study will include pregnant women. The pregnant women will participate&#xD;
      in the omental tissue collection, placenta collection, and the medical record review.&#xD;
&#xD;
      The study is expects a maximum enrollment of 114 pregnant women. This is because 52 omental&#xD;
      biopsies and 52 placentas are required to meet proposed statistical considerations.&#xD;
      Participants have the option of providing just one or both of the specimens. There is a&#xD;
      possibility as few as 52 participants could be enrolled and a maximum of 104 participants&#xD;
      could be enrolled to meet this requirement. There is an additional 10 participants enrollment&#xD;
      built into the enrollment number to allow for replacement of subjects based on lack of&#xD;
      clinical data in some participants, failure of tissue viability and hence experiments, and&#xD;
      thus a maximum of 114 (104+10) participants could be enrolled.&#xD;
&#xD;
      This required enrollment (52) is divided into two cohorts based on the diagnosis of&#xD;
      preeclampsia: 26 of each type of specimen in which the woman was diagnosed with preeclampsia&#xD;
      during her pregnancy, and 26 of each type of specimen in which the woman was not diagnosed&#xD;
      with preeclampsia during her pregnancy. Additionally, each cohort of 26 will be divided into&#xD;
      two groups based on gender of the fetus, 13 male fetuses and 13 female fetuses&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 20, 2018</start_date>
  <completion_date type="Anticipated">April 2027</completion_date>
  <primary_completion_date type="Anticipated">April 2027</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>Quantify the vascular AT2R expression and vascular function in placental and omental vascular arteries in both preeclamptic and controlled pregnancies.</measure>
    <time_frame>1 year</time_frame>
    <description>The researchers will measure the amount and distribution of vascular angiotensin II type 1 receptor (AT1R) and AT2R during normal human pregnancy and in preeclampsia. The researchers will assess if AT2R expression varies with severity of preeclampsia. Based on pilot data, the researchers expect decreased AT2R and increased AT1R protein levels in preeclamptic vs normotensive vessels.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To test if ex-vivo treatment of AT2R agonists reverses the endothelial dysfunction and improves vasoconstriction in the preeclamptic vessels.</measure>
    <time_frame>1 year</time_frame>
    <description>The researchers will quantify vascular AT2R expression and vascular function in placental and omental arteries of preeclamptic vs normal pregnant women. Vascular function studies will also test if ex vivo treatment with AT2R agonist reverses endothelial dysfunction and vasoconstriction in preeclamptic vessels.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To test AT2R mediated mechanisms on endothelial derived hyperpolarizing factor, nitric oxide and prostacyclin pathway of vascular relaxation to examine AT2's role in vaso-relaxation and AT2R mediated vasoconstrictor pathway will be defined.</measure>
    <time_frame>1 year</time_frame>
    <description>To test the AT2R-mediated mechanisms, endothelium-derived hyperpolarizing factor (EDHF), nitric oxide, and prostacyclin (PGI2) pathways of vascular relaxation and AT1R-mediated vasoconstrictor pathways will be determined. Also, the expression of endothelial nitric oxide synthase, its activity state, and signaling components of EDHF and PGI2 pathways, as well as nitrate/nitrite and PGI2 production and changes in membrane potential, will be measured</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">114</enrollment>
  <condition>Pre-Eclampsia</condition>
  <condition>Vascular Diseases</condition>
  <arm_group>
    <arm_group_label>Cohort 1 no Preeclampsia</arm_group_label>
    <description>Cohort 1: 26 mothers with no diagnosis of preeclampsia during pregnancy (13 male, 13 female neonate) Omental Biopsy and placental collection will be performed</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2 mild or severe Preeclampsia</arm_group_label>
    <description>Cohort 2: 26 mothers with diagnosis of mild or severe preeclampsia during pregnancy (13 male, 13 female neonate) Omental Biopsy and placental collection will be performed</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Omental Biopsy</intervention_name>
    <description>The surgeon and clinical care team will conduct the c-section to deliver the baby and the placenta as clinically indicated. After delivery, during the closing procedures, the surgeon will indicate a time for a participating Ob/Gyn physician on the study team to collect the omental bio-specimen. Omentum is frequently excised or removed for clinical reasons during surgical procedures. Omentum has small blood vessels within it that have been used for evaluation of vascular functional changes in research. The investigators wish to isolate one to three vessels of 5 to 7 cm length. The surgeon will then close and the clinical care team will resume their standard of care activities.</description>
    <arm_group_label>Cohort 1 no Preeclampsia</arm_group_label>
    <arm_group_label>Cohort 2 mild or severe Preeclampsia</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      omental tissue (research surgical excision) placental tissue (standard of care clinical&#xD;
      delivery)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Pregnant women with or without Preeclampsia who will be undergoing a C-section&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  female&#xD;
&#xD;
          -  Minimum age: 18&#xD;
&#xD;
          -  Maximum age: 40&#xD;
&#xD;
          -  Singleton births&#xD;
&#xD;
          -  Minimum gestational age at consent: 28 weeks, 0 days&#xD;
&#xD;
          -  Maximum gestational age at consent: 41 weeks, 0 days&#xD;
&#xD;
          -  Undergoing caesarean section, either planned or otherwise with or without trial of&#xD;
             labor&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Preexisting hypertension treated by antihypertensive agents during the prenatal&#xD;
             period. This will not include treatment of severe hypertension by antihypertensive or&#xD;
             use of magnesium sulfate after the patient is hospitalized for the diagnosis of&#xD;
             preeclampsia.&#xD;
&#xD;
          -  Any major fetal structural anomalies or aneuploidies&#xD;
&#xD;
          -  Preexisting conditions like pre-gestational type I or type II diabetes mellitus,&#xD;
             pre-pregnancy kidney disease with increased serum creatinine above 1.2 mg/dL, or other&#xD;
             underlying blood vessel problems like systemic lupus erythematosus or other autoimmune&#xD;
             conditions with evidence of pre-pregnancy proteinuria or hypertension.&#xD;
&#xD;
          -  Undergoing cesarean section for placental abruption or bleeding complications.&#xD;
&#xD;
          -  Singleton gestation not within 36 weeks, 0 days and 41 weeks, 0 days gestational age&#xD;
             at the time of enrollment (delivery)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Sathish Kumar, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sharon E Blohowiak, MS</last_name>
    <phone>6084176957</phone>
    <email>sblohowiak@wisc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rosalina Boeldt</last_name>
    <phone>608-417-4232</phone>
    <email>villalonland@wisc.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UnityPoint Health-Meriter Hospital</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53715</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sharon Blohowiak</last_name>
      <phone>608-417-6957</phone>
      <email>sblohowiak@wisc.edu</email>
    </contact>
    <investigator>
      <last_name>Sathish Kumar, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2022</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>Eclampsia</mesh_term>
    <mesh_term>Pre-Eclampsia</mesh_term>
    <mesh_term>Vascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 7, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03806283/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03806283
org study id: Meriter IRB 2018-006
secondary id: 5R01HL134779-02
secondary id: A532860
secondary id: SMPH/OBSTET & GYNECOL/OBSTET
secondary id: Protocol Version 10/25/2022
secondary id: 2018-1368
nct id: NCT03806283
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators will collect omental tissue (research surgical excision) and placental
      tissue (standard of care clinical delivery) from both preeclamptic and non-preeclamptic women
      during their c-section and use these samples to study the blood vessels, specifically the
      expression/activation of the AT2R.
Trial Design: The study is a comparison of two cohorts, those with and without preeclampsia
      during pregnancy. The team plans to investigate role of FABP4, PFAS and AT2 in modulation of
      vascular function/dysfunction using vessels isolated from the omental biopsies. The
      investigators will examine for the evidence of fetal vascular dysfunction mediated by
      decreased expression of AT2 in preeclampsia using vessels isolated from the placentas.

      Study Population: The study will include pregnant women. The pregnant women will participate
      in the omental tissue collection, placenta collection, and the medical record review.

      The study is expects a maximum enrollment of 114 pregnant women. This is because 52 omental
      biopsies and 52 placentas are required to meet proposed statistical considerations.
      Participants have the option of providing just one or both of the specimens. There is a
      possibility as few as 52 participants could be enrolled and a maximum of 104 participants
      could be enrolled to meet this requirement. There is an additional 10 participants enrollment
      built into the enrollment number to allow for replacement of subjects based on lack of
      clinical data in some participants, failure of tissue viability and hence experiments, and
      thus a maximum of 114 (104+10) participants could be enrolled.

      This required enrollment (52) is divided into two cohorts based on the diagnosis of
      preeclampsia: 26 of each type of specimen in which the woman was diagnosed with preeclampsia
      during her pregnancy, and 26 of each type of specimen in which the woman was not diagnosed
      with preeclampsia during her pregnancy. Additionally, each cohort of 26 will be divided into
      two groups based on gender of the fetus, 13 male fetuses and 13 female fetuses
observational model: Cohort
time perspective: Prospective
measure: Quantify the vascular AT2R expression and vascular function in placental and omental vascular arteries in both preeclamptic and controlled pregnancies.
time frame: 1 year
description: The researchers will measure the amount and distribution of vascular angiotensin II type 1 receptor (AT1R) and AT2R during normal human pregnancy and in preeclampsia. The researchers will assess if AT2R expression varies with severity of preeclampsia. Based on pilot data, the researchers expect decreased AT2R and increased AT1R protein levels in preeclamptic vs normotensive vessels.
measure: To test if ex-vivo treatment of AT2R agonists reverses the endothelial dysfunction and improves vasoconstriction in the preeclamptic vessels.
time frame: 1 year
description: The researchers will quantify vascular AT2R expression and vascular function in placental and omental arteries of preeclamptic vs normal pregnant women. Vascular function studies will also test if ex vivo treatment with AT2R agonist reverses endothelial dysfunction and vasoconstriction in preeclamptic vessels.
measure: To test AT2R mediated mechanisms on endothelial derived hyperpolarizing factor, nitric oxide and prostacyclin pathway of vascular relaxation to examine AT2's role in vaso-relaxation and AT2R mediated vasoconstrictor pathway will be defined.
time frame: 1 year
description: To test the AT2R-mediated mechanisms, endothelium-derived hyperpolarizing factor (EDHF), nitric oxide, and prostacyclin (PGI2) pathways of vascular relaxation and AT1R-mediated vasoconstrictor pathways will be determined. Also, the expression of endothelial nitric oxide synthase, its activity state, and signaling components of EDHF and PGI2 pathways, as well as nitrate/nitrite and PGI2 production and changes in membrane potential, will be measured
arm group label: Cohort 1 no Preeclampsia
description: Cohort 1: 26 mothers with no diagnosis of preeclampsia during pregnancy (13 male, 13 female neonate) Omental Biopsy and placental collection will be performed
arm group label: Cohort 2 mild or severe Preeclampsia
description: Cohort 2: 26 mothers with diagnosis of mild or severe preeclampsia during pregnancy (13 male, 13 female neonate) Omental Biopsy and placental collection will be performed
intervention type: Procedure
intervention name: Omental Biopsy
description: The surgeon and clinical care team will conduct the c-section to deliver the baby and the placenta as clinically indicated. After delivery, during the closing procedures, the surgeon will indicate a time for a participating Ob/Gyn physician on the study team to collect the omental bio-specimen. Omentum is frequently excised or removed for clinical reasons during surgical procedures. Omentum has small blood vessels within it that have been used for evaluation of vascular functional changes in research. The investigators wish to isolate one to three vessels of 5 to 7 cm length. The surgeon will then close and the clinical care team will resume their standard of care activities.
arm group label: Cohort 1 no Preeclampsia
arm group label: Cohort 2 mild or severe Preeclampsia
omental tissue (research surgical excision) placental tissue (standard of care clinical
      delivery)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 40 Years
last name: Sathish Kumar, PhD
role: Principal Investigator
affiliation: University of Wisconsin, Madison
last name: Sharon E Blohowiak, MS
phone: 6084176957
email: sblohowiak@wisc.edu
last name: Rosalina Boeldt
phone: 608-417-4232
email: villalonland@wisc.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Eclampsia
mesh term: Pre-Eclampsia
mesh term: Vascular Diseases
sharing ipd: No
provided document: 