<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/NCT02238301</url>
  </required_header>
  <id_info>
    <org_study_id>P130924</org_study_id>
    <nct_id>NCT02238301</nct_id>
  </id_info>
  <brief_title>Evaluation of Fetoplacental Oxygenation With Functional MRI in Pregnant Women</brief_title>
  <acronym>BOLD-FP</acronym>
  <official_title>Study of the Fetoplacental BOLD Effect in Pregnant Women Using Functional MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the use of functional MRI in pregnant women as a&#xD;
      non-invasive diagnostic tool to detect placental insufficiency and differentiate healthy&#xD;
      fetuses from the intra-uterine growth restricted ones. Functional MRI in pregnant women can&#xD;
      detect a variation of the MRI signal (called BOLD effect) from the placenta and the fetus&#xD;
      when the mother is breathing pure oxygen. This study aims hence to demonstrate the difference&#xD;
      in the BOLD effect between normal feto-placental units and growth restricted ones.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intrauterine growth restriction (IUGR) is associated with important maternal and perinatal&#xD;
      morbidity and mortality. IUGR is typically secondary to defective oxygenation, leading to&#xD;
      placental insufficiency.&#xD;
&#xD;
      Measurements made in the umbilical cord after puncture fetal blood showed that compared to&#xD;
      normal fetuses, fetuses with IUGR are often hypoxic, hypercapnic and acidotic. Pathological&#xD;
      placental and fetal oxygenation is considered as a main element of IUGR. To this day, there&#xD;
      is no non-invasive exploration method of this oxygenation. The only ways to monitor IUGR are&#xD;
      &quot;indirect&quot; ultrasonic analysis of fetal growth and uteroplacental Doppler spectra. Functional&#xD;
      BOLD (Blood Oxygen Level dependent) MRI, already used to investigate cerebral, tumor, cardiac&#xD;
      oxygenation, highlights local variations of oxygenation. The purpose of this study is to&#xD;
      obtain non invasive data of fetoplacental oxygenation through functional BOLD MRI. Comparing&#xD;
      data on eutrophic fetuses and IUGR fetuses will determine the potential contribution of this&#xD;
      technique in the diagnosis, treatment and medical management of dysfunctional placentas&#xD;
      associated with an increased risk of IUGR.&#xD;
&#xD;
      a fetal MRI in the pediatric radiology department of Necker-Enfants Malades Hospital or&#xD;
      Robert Debré Hospital, for fetal or placental indications as part of usual workup, will be&#xD;
      invited to participate in this protocol. At the waning of the scheduled fetal MRI, patients&#xD;
      will subsequently receive an additional BOLD and ASL sequence before and after maternal&#xD;
      hyperoxygenation.&#xD;
&#xD;
      Patients will be included in three centers : Necker Hospital, Robert Debré Hospital and Louis&#xD;
      Mourier Hospital. Only at Necker Hospital: a subgroup of patients will be included at the&#xD;
      beginning of the protocol for the adjustment of the settings of the MRI machine, for the&#xD;
      determination of BOLD sequences' parameters, as well as the selection of the most adapted&#xD;
      type of oxygenation mask.&#xD;
&#xD;
      In the three centers, investigators will include patients with IUGR fetuses and patients with&#xD;
      a eutrophic fetus.&#xD;
&#xD;
      A total of two visits (selection visit and baseline) are scheduled for all patients in this&#xD;
      trial. Patient selection will be done during a ultrasound visit. Patients can give their&#xD;
      consent on the same day or on the MRI appointment day; in all cases the consent will be&#xD;
      signed on the day of the appointment MRI.&#xD;
&#xD;
      The flow and duration of the oxygenation of the initial group &quot;test patients&quot; will be&#xD;
      determined before completion of the examination; for other patients, the flow rate will be&#xD;
      determined based on the results of this first group.&#xD;
&#xD;
      The duration of the BOLD sequence will be around 10 minutes. The sequences will focus on the&#xD;
      feto-placental unit.&#xD;
&#xD;
      A first BOLD sequence will be launched under ambient air. The second BOLD sequence will be&#xD;
      repeated after 5 minutes of maternal hyperoxygenation.&#xD;
&#xD;
      MRI data will be saved and analyzed at the Laboratory of Imaging Research of the team 2 of&#xD;
      Paris Cardiovascular Research Center (INSERM U970).&#xD;
&#xD;
      The data necessary for the statistical analysis of the study are collected from the medical&#xD;
      file of patients included in the study. Data entry will be performed by a research technician&#xD;
      on electronic media via an internet browser.&#xD;
&#xD;
      The inclusion period will be of 57 months. Each woman's duration of participation will be 1&#xD;
      hour. The maximum duration of the study will be 57 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 18, 2015</start_date>
  <completion_date type="Actual">September 26, 2019</completion_date>
  <primary_completion_date type="Actual">September 26, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Highlight a placental BOLD effect</measure>
    <time_frame>at inclusion</time_frame>
    <description>Measured as the difference between the T2* of the placenta under the ambient air and under hyperoxygenation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with positive difference of signal intensity of maternal liver, under the ambient air and under hyperoxygenation</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BOLD effect in the fetal liver and brain of eutrophic fetuses</measure>
    <time_frame>at inclusion</time_frame>
    <description>Measure the BOLD effect in the fetal liver and brain of eutrophic fetuses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BOLD effect in the fetal liver and brain of IUGR fetuses</measure>
    <time_frame>at inclusion</time_frame>
    <description>Measure the BOLD effect in the fetal liver and brain of IUGR fetuses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BOLD effect in the maternal liver of IUGR fetuses</measure>
    <time_frame>at inclusion</time_frame>
    <description>Measure a Bold effect in the maternal liver of IUGR fetuses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measure a Bold effect in the placenta of IUGR fetuses</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility : number of possible perfusion measure</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility : percent of possible perfusion measure</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compare the placental perfusion between eutrophic and RCIU fetuses</measure>
    <time_frame>at inclusion</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">101</enrollment>
  <condition>Intrauterine Growth Restriction</condition>
  <arm_group>
    <arm_group_label>Patients &quot;test&quot; (pregnant women with a eutrophic fetus)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Test the type of mask, oxygen flow and duration of oxygenation, adjustment of MRI machine Adjustment of MRI machine (choice of antenna calibration, verifying Settings of each sequence, adaptation of the number of cuts for the duration of each sequence, checking the correct execution of the succession of sequences, settings of total examination time)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pregnant women with a diagnosis of IUGR fetuses</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Measure of the BOLD effect in the feto-placental units of IUGR fetuses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pregnant women with eutrophic fetuses</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Measure of BOLD effects of fetal-placental unit eutrophic fetuses</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Bold sequence patients test</intervention_name>
    <description>Develop the hyperventilation protocol (speed, duration ...) and the choice of type of mask oxygenation better tolerated by patients. Sequences beginning with a low oxygen flow (2L/mn) then progressively increasing to obtain the BOLD effect required</description>
    <arm_group_label>Patients &quot;test&quot; (pregnant women with a eutrophic fetus)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Bold + ASL sequence</intervention_name>
    <description>A first sequence BOLD+ASL will be launched in ambient air. The second sequence is repeated BOLD 5 minutes after power maternal hyperventilation.&#xD;
Sequences will focus on the fetus and placenta but will also include maternal liver to validate maternal hyperoxygenation.</description>
    <arm_group_label>Pregnant women with a diagnosis of IUGR fetuses</arm_group_label>
    <arm_group_label>Pregnant women with eutrophic fetuses</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Major patient&#xD;
&#xD;
          -  Patient with a singleton pregnancy&#xD;
&#xD;
          -  Patient between 18 and 37 gestational weeks&#xD;
&#xD;
          -  Informed consent signed by the patient&#xD;
&#xD;
          -  Patient affiliated to a social security scheme (beneficiary or assignee) Specific&#xD;
             criteria for patients with a eutrophic fetus&#xD;
&#xD;
          -  Patient with fetal eutrophic on sonographic fetal weight estimation Specific criteria&#xD;
             for patients with an IUGR-fetus Patient with a fetus presenting intra-uterine growth&#xD;
             restriction diagnosed by ultrasound (&lt;5th percentile).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with the usual contra-indications for MRI&#xD;
&#xD;
          -  Patient with an abdominal circumference&gt; 125 cm&#xD;
&#xD;
          -  Patient with a multiple pregnancy&#xD;
&#xD;
          -  Patient with placenta accreta or percreta&#xD;
&#xD;
          -  Patient with a pregnancy after long history of infertility and medically assisted&#xD;
             procreation&#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>Laurent SALOMON, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Hospital Necker - Enfants Malades - Public Hospitals of Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Necker - Enfants Malades Hospital (Assistance Publique des Hopitaux de Paris)</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>September 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <last_update_submitted>April 2, 2021</last_update_submitted>
  <last_update_submitted_qc>April 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Intrauterine growth restriction</keyword>
  <keyword>BOLD effect</keyword>
  <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/NCT02238301
org study id: P130924
nct id: NCT02238301
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the use of functional MRI in pregnant women as a
      non-invasive diagnostic tool to detect placental insufficiency and differentiate healthy
      fetuses from the intra-uterine growth restricted ones. Functional MRI in pregnant women can
      detect a variation of the MRI signal (called BOLD effect) from the placenta and the fetus
      when the mother is breathing pure oxygen. This study aims hence to demonstrate the difference
      in the BOLD effect between normal feto-placental units and growth restricted ones.
Intrauterine growth restriction (IUGR) is associated with important maternal and perinatal
      morbidity and mortality. IUGR is typically secondary to defective oxygenation, leading to
      placental insufficiency.

      Measurements made in the umbilical cord after puncture fetal blood showed that compared to
      normal fetuses, fetuses with IUGR are often hypoxic, hypercapnic and acidotic. Pathological
      placental and fetal oxygenation is considered as a main element of IUGR. To this day, there
      is no non-invasive exploration method of this oxygenation. The only ways to monitor IUGR are
      "indirect" ultrasonic analysis of fetal growth and uteroplacental Doppler spectra. Functional
      BOLD (Blood Oxygen Level dependent) MRI, already used to investigate cerebral, tumor, cardiac
      oxygenation, highlights local variations of oxygenation. The purpose of this study is to
      obtain non invasive data of fetoplacental oxygenation through functional BOLD MRI. Comparing
      data on eutrophic fetuses and IUGR fetuses will determine the potential contribution of this
      technique in the diagnosis, treatment and medical management of dysfunctional placentas
      associated with an increased risk of IUGR.

      a fetal MRI in the pediatric radiology department of Necker-Enfants Malades Hospital or
      Robert Debré Hospital, for fetal or placental indications as part of usual workup, will be
      invited to participate in this protocol. At the waning of the scheduled fetal MRI, patients
      will subsequently receive an additional BOLD and ASL sequence before and after maternal
      hyperoxygenation.

      Patients will be included in three centers : Necker Hospital, Robert Debré Hospital and Louis
      Mourier Hospital. Only at Necker Hospital: a subgroup of patients will be included at the
      beginning of the protocol for the adjustment of the settings of the MRI machine, for the
      determination of BOLD sequences' parameters, as well as the selection of the most adapted
      type of oxygenation mask.

      In the three centers, investigators will include patients with IUGR fetuses and patients with
      a eutrophic fetus.

      A total of two visits (selection visit and baseline) are scheduled for all patients in this
      trial. Patient selection will be done during a ultrasound visit. Patients can give their
      consent on the same day or on the MRI appointment day; in all cases the consent will be
      signed on the day of the appointment MRI.

      The flow and duration of the oxygenation of the initial group "test patients" will be
      determined before completion of the examination; for other patients, the flow rate will be
      determined based on the results of this first group.

      The duration of the BOLD sequence will be around 10 minutes. The sequences will focus on the
      feto-placental unit.

      A first BOLD sequence will be launched under ambient air. The second BOLD sequence will be
      repeated after 5 minutes of maternal hyperoxygenation.

      MRI data will be saved and analyzed at the Laboratory of Imaging Research of the team 2 of
      Paris Cardiovascular Research Center (INSERM U970).

      The data necessary for the statistical analysis of the study are collected from the medical
      file of patients included in the study. Data entry will be performed by a research technician
      on electronic media via an internet browser.

      The inclusion period will be of 57 months. Each woman's duration of participation will be 1
      hour. The maximum duration of the study will be 57 months.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Highlight a placental BOLD effect
time frame: at inclusion
description: Measured as the difference between the T2* of the placenta under the ambient air and under hyperoxygenation.
measure: Number of patients with positive difference of signal intensity of maternal liver, under the ambient air and under hyperoxygenation
time frame: at inclusion
measure: BOLD effect in the fetal liver and brain of eutrophic fetuses
time frame: at inclusion
description: Measure the BOLD effect in the fetal liver and brain of eutrophic fetuses
measure: BOLD effect in the fetal liver and brain of IUGR fetuses
time frame: at inclusion
description: Measure the BOLD effect in the fetal liver and brain of IUGR fetuses
measure: BOLD effect in the maternal liver of IUGR fetuses
time frame: at inclusion
description: Measure a Bold effect in the maternal liver of IUGR fetuses
measure: Measure a Bold effect in the placenta of IUGR fetuses
time frame: at inclusion
measure: Feasibility : number of possible perfusion measure
time frame: at inclusion
measure: Feasibility : percent of possible perfusion measure
time frame: at inclusion
measure: Compare the placental perfusion between eutrophic and RCIU fetuses
time frame: at inclusion
arm group label: Patients "test" (pregnant women with a eutrophic fetus)
arm group type: Other
description: Test the type of mask, oxygen flow and duration of oxygenation, adjustment of MRI machine Adjustment of MRI machine (choice of antenna calibration, verifying Settings of each sequence, adaptation of the number of cuts for the duration of each sequence, checking the correct execution of the succession of sequences, settings of total examination time)
arm group label: Pregnant women with a diagnosis of IUGR fetuses
arm group type: Active Comparator
description: Measure of the BOLD effect in the feto-placental units of IUGR fetuses
arm group label: Pregnant women with eutrophic fetuses
arm group type: Active Comparator
description: Measure of BOLD effects of fetal-placental unit eutrophic fetuses
intervention type: Other
intervention name: Bold sequence patients test
description: Develop the hyperventilation protocol (speed, duration ...) and the choice of type of mask oxygenation better tolerated by patients. Sequences beginning with a low oxygen flow (2L/mn) then progressively increasing to obtain the BOLD effect required
arm group label: Patients "test" (pregnant women with a eutrophic fetus)
intervention type: Other
intervention name: Bold + ASL sequence
description: A first sequence BOLD+ASL will be launched in ambient air. The second sequence is repeated BOLD 5 minutes after power maternal hyperventilation.
Sequences will focus on the fetus and placenta but will also include maternal liver to validate maternal hyperoxygenation.
arm group label: Pregnant women with a diagnosis of IUGR fetuses
arm group label: Pregnant women with eutrophic fetuses
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laurent SALOMON, MD, PhD
role: Study Director
affiliation: Hospital Necker - Enfants Malades - Public Hospitals of Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Fetal Growth Retardation