<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/NCT04506970</url>
  </required_header>
  <id_info>
    <org_study_id>20-000991</org_study_id>
    <nct_id>NCT04506970</nct_id>
  </id_info>
  <brief_title>Predicting Placental Pathologies by Ultrasound Imaging</brief_title>
  <official_title>Predicting Placental Pathologies by Ultrasound Imaging of the Human Placenta During Gestation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</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>
      Intrauterine growth restriction (IUGR) is caused when the placenta cannot provide enough&#xD;
      nutrients to allow normal growth of the fetus during pregnancy. It is unclear why IUGR&#xD;
      happens, but an increase in inflammatory T cells in the placenta known as villitis of unknown&#xD;
      etiology (VUE) is observed in many IUGR infants. The investigators aim to develop ultrasound&#xD;
      methods for diagnosing VUE to understand it's role in IUGR.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intrauterine growth restriction (IUGR) occurs in 3-10% of all pregnancies and is associated&#xD;
      with significant morbidity and mortality during pregnancy, after birth and throughout the&#xD;
      child's lifespan. IUGR is caused by the inability of the placental vasculature to provide&#xD;
      enough oxygen and nutrients to support the fetus; yet, the mechanisms leading to disruption&#xD;
      of placental vasculature are unknown. The placenta of ~50% of IUGR fetuses are infiltrated&#xD;
      with inflammatory cells, specifically maternal T cells, which destroy placental blood vessels&#xD;
      that support the fetus. This infiltration of T cells is known as villitis of unknown etiology&#xD;
      (VUE). The diagnosis of VUE is problematic because it occurs without clinical signs and&#xD;
      symptoms of maternal (or fetal) distress and puts the fetus at significant risk of demise.&#xD;
      Additionally, VUE commonly recurs in subsequent pregnancies putting future offspring at risk.&#xD;
      Yet, the exact prevalence of VUE and its significance in IUGR pathogenesis and outcomes are&#xD;
      poorly understood as VUE is only diagnosed after the infant is outside the womb. Therefore,&#xD;
      the study aims to recognize risk factors and cellular mechanisms associated with VUE and&#xD;
      develop methods for diagnosing and treating VUE in utero, in order to improve infant health.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 27, 2020</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Uterine artery indices</measure>
    <time_frame>34-36 weeks</time_frame>
    <description>Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Umbilical artery indices</measure>
    <time_frame>34-36 weeks</time_frame>
    <description>Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systolic(S)/diastolic(D) ratio</measure>
    <time_frame>34-36 weeks</time_frame>
    <description>S = Systolic peak (max velocity); Maximum velocity during contraction of the fetal heart.&#xD;
D = End-diastolic flow; Continuing forward flow in the umbilical artery during the relaxation phase of the heartbeat.&#xD;
S/D ratio = (systolic / diastolic ratio)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Resistance index (RI)</measure>
    <time_frame>34-36 weeks</time_frame>
    <description>Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulsatility index (PI)</measure>
    <time_frame>34-36 weeks</time_frame>
    <description>Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Placental pathology</measure>
    <time_frame>up to 42 weeks</time_frame>
    <description>Using the Amsterdam criteria, following delivery, placentae will be histologically examined for placental villitis (presence of maternal T cells) and graded by severity. High grade involves greater than 10 villi while low grade affects fewer than 10 villi.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Intrauterine Growth Restriction</condition>
  <condition>Villitis</condition>
  <condition>IUGR</condition>
  <arm_group>
    <arm_group_label>Intrauterine Growth Restriction</arm_group_label>
    <description>Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (&gt;28 weeks gestation)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal pregnancy</arm_group_label>
    <description>Pregnant women identified with an uncomplicated pregnancy during the third trimester (&gt;28 weeks), matched for fetal sex and gestational age with women enrolled in the IUGR group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Comprehensive Doppler Ultrasound of the Placenta</intervention_name>
    <description>Ultrasound measures to be collected include uterine artery (UtA) and umbilical artery (UA), systolic/diastolic (S/D) ratio, resistance index (RI), pulsatility index (PI) and presence of early diastolic notch.</description>
    <arm_group_label>Intrauterine Growth Restriction</arm_group_label>
    <arm_group_label>Normal pregnancy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging)</intervention_name>
    <description>In addition, a Verasonics ultrasound scanner will be used for ultra-sensitive Doppler imaging. Data will be collected on vessel density, periphery-to-center vessel density ratio (VDR) and microvessel morphology.</description>
    <arm_group_label>Intrauterine Growth Restriction</arm_group_label>
    <arm_group_label>Normal pregnancy</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Participants will be recruited from women obtaining prenatal care in the obstetrics clinic&#xD;
        at Mayo Clinic in Rochester, Minnesota. This study will consist of two cohorts: 1) women&#xD;
        diagnosed with intrauterine growth restriction (IUGR) and 2) women having uncomplicated&#xD;
        pregnancies. Forty women will be enrolled after being diagnosed with IUGR. Based on prior&#xD;
        clinical data it is expected that 50% will have a VUE diagnosis. Another cohort of 20 women&#xD;
        having uncomplicated pregnancies will also be enrolled, matched for fetal sex and&#xD;
        gestational age at ultrasound.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria for IUGR study cohort:&#xD;
&#xD;
          -  Pregnancy &gt; 28 weeks gestation&#xD;
&#xD;
          -  Diagnosis of Intrauterine Growth Restriction (IUGR) before admission for labor and&#xD;
             delivery&#xD;
&#xD;
          -  Weight &gt; 110 lbs (50 kg)&#xD;
&#xD;
          -  Ability to understand and provide written informed consent&#xD;
&#xD;
        Inclusion Criteria for control cohort:&#xD;
&#xD;
          -  Pregnancy &gt; 28 weeks gestation&#xD;
&#xD;
          -  No known pregnancy complications at prenatal obstetrical visit (+/- 1 week gestational&#xD;
             age of matched subject in IUGR cohort)&#xD;
&#xD;
          -  Weight &gt; 110 lbs (50 kg)&#xD;
&#xD;
          -  Ability to understand and provide written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known immunodeficiency or pregnancy complication (i.e. preeclampsia or gestational&#xD;
             diabetes)&#xD;
&#xD;
          -  Known autoimmune disease (e.g., rheumatoid arthritis or systemic lupus erythematosus)&#xD;
             or chronic hypertension&#xD;
&#xD;
          -  Chronic, active viral infections, including HIV-1/2, HTLV-1/2, Hepatitis B or C&#xD;
&#xD;
          -  Solid organ or transplant recipient&#xD;
&#xD;
          -  Current smokers (tobacco exposure within 30 days of registration)&#xD;
&#xD;
          -  Conceptions from assisted reproductive technology (prior Clomid use is allowed)&#xD;
&#xD;
          -  Multiple gestation&#xD;
&#xD;
          -  Ruptured membranes&#xD;
&#xD;
          -  Pregnancy &lt;28 weeks gestation&#xD;
&#xD;
          -  Not planning on delivering at Mayo Clinic&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mauro Schenone, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Elizabeth Ann L Enninga, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emily N Smith, BSN</last_name>
    <phone>507-266-4813</phone>
    <email>smith.emily3@mayo.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maureen A Lemens, BSN</last_name>
    <phone>507-293-1487</phone>
    <email>lemens.maureen@mayo.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emily N Smith, BSN</last_name>
      <phone>507-266-4813</phone>
      <email>smith.emily3@mayo.edu</email>
    </contact>
    <contact_backup>
      <last_name>Maureen A Lemens, BSN</last_name>
      <phone>507-293-1487</phone>
      <email>lemens.maureen@mayo.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>March 22, 2023</last_update_submitted>
  <last_update_submitted_qc>March 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Mauro H. Schenone</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fetal Growth Retardation</mesh_term>
  </condition_browse>
  <!-- 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/NCT04506970
org study id: 20-000991
nct id: NCT04506970
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Intrauterine growth restriction (IUGR) is caused when the placenta cannot provide enough
      nutrients to allow normal growth of the fetus during pregnancy. It is unclear why IUGR
      happens, but an increase in inflammatory T cells in the placenta known as villitis of unknown
      etiology (VUE) is observed in many IUGR infants. The investigators aim to develop ultrasound
      methods for diagnosing VUE to understand it's role in IUGR.
Intrauterine growth restriction (IUGR) occurs in 3-10% of all pregnancies and is associated
      with significant morbidity and mortality during pregnancy, after birth and throughout the
      child's lifespan. IUGR is caused by the inability of the placental vasculature to provide
      enough oxygen and nutrients to support the fetus; yet, the mechanisms leading to disruption
      of placental vasculature are unknown. The placenta of ~50% of IUGR fetuses are infiltrated
      with inflammatory cells, specifically maternal T cells, which destroy placental blood vessels
      that support the fetus. This infiltration of T cells is known as villitis of unknown etiology
      (VUE). The diagnosis of VUE is problematic because it occurs without clinical signs and
      symptoms of maternal (or fetal) distress and puts the fetus at significant risk of demise.
      Additionally, VUE commonly recurs in subsequent pregnancies putting future offspring at risk.
      Yet, the exact prevalence of VUE and its significance in IUGR pathogenesis and outcomes are
      poorly understood as VUE is only diagnosed after the infant is outside the womb. Therefore,
      the study aims to recognize risk factors and cellular mechanisms associated with VUE and
      develop methods for diagnosing and treating VUE in utero, in order to improve infant health.
observational model: Case-Control
time perspective: Prospective
measure: Uterine artery indices
time frame: 34-36 weeks
description: Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5
measure: Umbilical artery indices
time frame: 34-36 weeks
description: Measured by Doppler and 3D microvessel imaging, used to calculate outcomes 3-5
measure: Systolic(S)/diastolic(D) ratio
time frame: 34-36 weeks
description: S = Systolic peak (max velocity); Maximum velocity during contraction of the fetal heart.
D = End-diastolic flow; Continuing forward flow in the umbilical artery during the relaxation phase of the heartbeat.
S/D ratio = (systolic / diastolic ratio)
measure: Resistance index (RI)
time frame: 34-36 weeks
description: Resistance index (RI) = (systolic velocity - diastolic velocity / systolic velocity)
measure: Pulsatility index (PI)
time frame: 34-36 weeks
description: Pulsatility index (PI) = (systolic velocity - diastolic velocity / mean velocity)
measure: Placental pathology
time frame: up to 42 weeks
description: Using the Amsterdam criteria, following delivery, placentae will be histologically examined for placental villitis (presence of maternal T cells) and graded by severity. High grade involves greater than 10 villi while low grade affects fewer than 10 villi.
arm group label: Intrauterine Growth Restriction
description: Pregnant women carrying a fetus identified with intrauterine growth restriction during the third trimester (>28 weeks gestation)
arm group label: Normal pregnancy
description: Pregnant women identified with an uncomplicated pregnancy during the third trimester (>28 weeks), matched for fetal sex and gestational age with women enrolled in the IUGR group.
intervention type: Diagnostic Test
intervention name: Comprehensive Doppler Ultrasound of the Placenta
description: Ultrasound measures to be collected include uterine artery (UtA) and umbilical artery (UA), systolic/diastolic (S/D) ratio, resistance index (RI), pulsatility index (PI) and presence of early diastolic notch.
arm group label: Intrauterine Growth Restriction
arm group label: Normal pregnancy
intervention type: Other
intervention name: Verasonics Ultrasound scanner (ultra-sensitive Doppler imaging)
description: In addition, a Verasonics ultrasound scanner will be used for ultra-sensitive Doppler imaging. Data will be collected on vessel density, periphery-to-center vessel density ratio (VDR) and microvessel morphology.
arm group label: Intrauterine Growth Restriction
arm group label: Normal pregnancy
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Mauro Schenone, MD
role: Principal Investigator
affiliation: Mayo Clinic
last name: Elizabeth Ann L Enninga, PhD
role: Study Chair
affiliation: Mayo Clinic
last name: Emily N Smith, BSN
phone: 507-266-4813
email: smith.emily3@mayo.edu
last name: Maureen A Lemens, BSN
phone: 507-293-1487
email: lemens.maureen@mayo.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Mauro H. Schenone
investigator title: Principal Investigator
mesh term: Fetal Growth Retardation