<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/NCT03032991</url>
  </required_header>
  <id_info>
    <org_study_id>SAF2015-69265</org_study_id>
    <nct_id>NCT03032991</nct_id>
  </id_info>
  <brief_title>Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers</brief_title>
  <acronym>GD-BRAIN</acronym>
  <official_title>Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers (GD-BRAIN)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad de Murcia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universidad de Granada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidad de Murcia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prospective multicenter study GD-Brain provides a better knowledge on the basis of&#xD;
      neurological impairment in children born to mothers with gestational diabetes (GDM). GDM&#xD;
      modifies placental structure and affect materno-fetal nutrient transfer. Docosahexaenoic acid&#xD;
      (DHA) play an important role on neurodevelopment, and it is reduced in venous cord blood of&#xD;
      newborns born to GDM. In previous studies, we have already demonstrated impaired DHA fetal&#xD;
      levels not only using label fatty acids with stable isotopes administrated to pregnant women,&#xD;
      but also in observational studies in GDM as the prevention of obesity study (PREOBE study) in&#xD;
      Granada and other similar study in Murcia. The impaired cord DHA levels were associated to&#xD;
      disturbed neurodevelopment in these children during the first year of life. However, it is&#xD;
      uncertain the mechanisms underlying this impaired materno-fetal DHA transfer and implications&#xD;
      for later life.&#xD;
&#xD;
      The recent publication in Nature Journal of a selective transmembrane carrier for DHA in&#xD;
      brain named &quot;major facilitator superfamily domain 2a&quot; (MFSD2a) open new expectations. We&#xD;
      detected disturbed MFSD2a levels in placentas from GDM which could be due to structural&#xD;
      problems in this organ; inflammation, oxidation and metabolic changes related to diabetes&#xD;
      might affect MFSD2a activity. Moreover, it is difficult to know whether disturbed MFSD2a&#xD;
      levels in placenta may also indicate altered levels of this carrier in the brain from&#xD;
      children born to GDM mothers, which could contribute to neurodevelopment impairment in these&#xD;
      subjects. Recent studies also indicate that obesity alters the biosynthesis of eicosanoids&#xD;
      derived from DHA, with a decrease of protectins and resolvin of D-series, which have powerful&#xD;
      anti-inflammatory properties.&#xD;
&#xD;
      The main aim of this study is to analyse potential differences on neurodevelopment, and brain&#xD;
      structure and functioning, in children 8 years old born to GDM respect to those born to&#xD;
      healthy normoweight mothers, as well as to identify early biomarkers consistently related to&#xD;
      neurodevelopment from early stages of life.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We will contact to participants from the PREOBE study and Murcia's cohorts study to get&#xD;
      involved a total of 174 children at 8 years of age. The results from neurodevelopment&#xD;
      evaluation by neuropsychological testing, neurological functions rhythms and neuroimaging&#xD;
      (fMRI and DTI) at 8 years old will be associated to clinical and metabolic data recorded&#xD;
      during pregnancy.&#xD;
&#xD;
      As secondary aim, we would discern whether the decrease on DHA levels in offspring of GDM at&#xD;
      birth is associated to disturbed neurodevelopment at 8 years old.&#xD;
&#xD;
      The impact of maternal diabetes on placental MFSD2a and children's resolvin and protectins&#xD;
      derived from DHA will be measured in urine samples at 8 years old.&#xD;
&#xD;
      Gut microbiota composition and function will be also studied to detect its role in the&#xD;
      potential disturbances regarding the production of anti-inflammatory mediators.&#xD;
&#xD;
      A part from the clinical study, we will perform an intervention trial using animal models.&#xD;
      Gestational rats with diabetes and control rats will be treated with antioxidants and&#xD;
      adipoRon in order to delay neuro-degeneration in these animals because of the diabetes, as&#xD;
      well as their influence on MFSD2a levels in placenta and brain. All these studies may provide&#xD;
      to the industry of valuable information to improve nutritional supplements during gestation&#xD;
      or infancy to avoid potential delay of cognitive functions in offspring of diabetic mothers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2016</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Neuropsychological battery</measure>
    <time_frame>8 years old</time_frame>
    <description>Neuropsychological battery to cover different neuropsychological domains: processing speed, memory, attention, language, executive functions, and behaviour (parent-completed measure).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Neuroimaging ( functional MRI)</measure>
    <time_frame>8 years</time_frame>
    <description>Anatomical magnetic resonance imaging (fMRI)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electroencephalography (EEG)</measure>
    <time_frame>8 years</time_frame>
    <description>Stereotyped electrophysiological response to several external stimulus</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Fatty acids</measure>
    <time_frame>8 years old</time_frame>
    <description>Fatty acid profile in oral mucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolomic</measure>
    <time_frame>8 years old</time_frame>
    <description>Prostaglandins, thromboxans, isoprostanes, resolvin in urine samples</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Microbiome</measure>
    <time_frame>8 years old</time_frame>
    <description>Metagenome</description>
  </other_outcome>
  <other_outcome>
    <measure>Maturation of circadian rhythm</measure>
    <time_frame>8 years old</time_frame>
    <description>Analysis of the circadian rhythm of temperature, activity and sleep</description>
  </other_outcome>
  <other_outcome>
    <measure>Nutritional evaluation</measure>
    <time_frame>8 years old</time_frame>
    <description>Dietary assessment by food frequency questionnaire and by 3 day of dietary record</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical activity</measure>
    <time_frame>8 years old</time_frame>
    <description>questionnaires</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical Activity</measure>
    <time_frame>8 years old</time_frame>
    <description>Accelerometers will be used also to record activity of the subjects</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">174</enrollment>
  <condition>Gestational Diabetes Mellitus in Childbirth</condition>
  <condition>Neurodevelopmental Disorders</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Children at 8 years old born from healthy pregnancies</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GDM</arm_group_label>
    <description>Children at 8 years old born from mothers with gestational diabetes during pregnancy</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Saliva, urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        174 Children born between 2008-2011 from 2 previous studies:&#xD;
&#xD;
          -  PREOBE study from the University of Granada&#xD;
&#xD;
          -  GDM Murcia study from the University of Murcia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children from healthy pregnancies and GDM pregnancies from the ^PREOBE study and GDM&#xD;
             Murcia study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>9 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Elvira Larqué, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad de Murcia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cristina Campoy, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universidad de Granada</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Elvira Larqué, Dr</last_name>
    <phone>0034868884239</phone>
    <email>elvirada@um.es</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Cristina Campoy, MD</last_name>
    <phone>0034958240740</phone>
    <email>ccampoy@ugr.es</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Elvira Larqué</name>
      <address>
        <city>Murcia</city>
        <zip>30100</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elvira Larqué, Dr</last_name>
      <phone>0034868884239</phone>
      <email>elvirada@um.es</email>
    </contact>
    <contact_backup>
      <last_name>Cristina Campoy, MD</last_name>
      <phone>0034958240740</phone>
      <email>ccampoy@ugr.es</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>January 23, 2017</last_update_submitted>
  <last_update_submitted_qc>January 23, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 26, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad de Murcia</investigator_affiliation>
    <investigator_full_name>Elvira Larqué</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Gestational diabetes</keyword>
  <keyword>Neurodevelopment</keyword>
  <keyword>Placenta</keyword>
  <keyword>Gut microbiota</keyword>
  <keyword>Protectins</keyword>
  <keyword>MFSD2a</keyword>
  <keyword>AdipoRon</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</mesh_term>
    <mesh_term>Neurodevelopmental Disorders</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/NCT03032991
org study id: SAF2015-69265
nct id: NCT03032991
lead sponsor: 
collaborator: 
has dmc: No
The prospective multicenter study GD-Brain provides a better knowledge on the basis of
      neurological impairment in children born to mothers with gestational diabetes (GDM). GDM
      modifies placental structure and affect materno-fetal nutrient transfer. Docosahexaenoic acid
      (DHA) play an important role on neurodevelopment, and it is reduced in venous cord blood of
      newborns born to GDM. In previous studies, we have already demonstrated impaired DHA fetal
      levels not only using label fatty acids with stable isotopes administrated to pregnant women,
      but also in observational studies in GDM as the prevention of obesity study (PREOBE study) in
      Granada and other similar study in Murcia. The impaired cord DHA levels were associated to
      disturbed neurodevelopment in these children during the first year of life. However, it is
      uncertain the mechanisms underlying this impaired materno-fetal DHA transfer and implications
      for later life.

      The recent publication in Nature Journal of a selective transmembrane carrier for DHA in
      brain named "major facilitator superfamily domain 2a" (MFSD2a) open new expectations. We
      detected disturbed MFSD2a levels in placentas from GDM which could be due to structural
      problems in this organ; inflammation, oxidation and metabolic changes related to diabetes
      might affect MFSD2a activity. Moreover, it is difficult to know whether disturbed MFSD2a
      levels in placenta may also indicate altered levels of this carrier in the brain from
      children born to GDM mothers, which could contribute to neurodevelopment impairment in these
      subjects. Recent studies also indicate that obesity alters the biosynthesis of eicosanoids
      derived from DHA, with a decrease of protectins and resolvin of D-series, which have powerful
      anti-inflammatory properties.

      The main aim of this study is to analyse potential differences on neurodevelopment, and brain
      structure and functioning, in children 8 years old born to GDM respect to those born to
      healthy normoweight mothers, as well as to identify early biomarkers consistently related to
      neurodevelopment from early stages of life.
We will contact to participants from the PREOBE study and Murcia's cohorts study to get
      involved a total of 174 children at 8 years of age. The results from neurodevelopment
      evaluation by neuropsychological testing, neurological functions rhythms and neuroimaging
      (fMRI and DTI) at 8 years old will be associated to clinical and metabolic data recorded
      during pregnancy.

      As secondary aim, we would discern whether the decrease on DHA levels in offspring of GDM at
      birth is associated to disturbed neurodevelopment at 8 years old.

      The impact of maternal diabetes on placental MFSD2a and children's resolvin and protectins
      derived from DHA will be measured in urine samples at 8 years old.

      Gut microbiota composition and function will be also studied to detect its role in the
      potential disturbances regarding the production of anti-inflammatory mediators.

      A part from the clinical study, we will perform an intervention trial using animal models.
      Gestational rats with diabetes and control rats will be treated with antioxidants and
      adipoRon in order to delay neuro-degeneration in these animals because of the diabetes, as
      well as their influence on MFSD2a levels in placenta and brain. All these studies may provide
      to the industry of valuable information to improve nutritional supplements during gestation
      or infancy to avoid potential delay of cognitive functions in offspring of diabetic mothers.
observational model: Case-Control
time perspective: Prospective
measure: Neuropsychological battery
time frame: 8 years old
description: Neuropsychological battery to cover different neuropsychological domains: processing speed, memory, attention, language, executive functions, and behaviour (parent-completed measure).
measure: Neuroimaging ( functional MRI)
time frame: 8 years
description: Anatomical magnetic resonance imaging (fMRI)
measure: Electroencephalography (EEG)
time frame: 8 years
description: Stereotyped electrophysiological response to several external stimulus
measure: Fatty acids
time frame: 8 years old
description: Fatty acid profile in oral mucose
measure: Metabolomic
time frame: 8 years old
description: Prostaglandins, thromboxans, isoprostanes, resolvin in urine samples
measure: Microbiome
time frame: 8 years old
description: Metagenome
measure: Maturation of circadian rhythm
time frame: 8 years old
description: Analysis of the circadian rhythm of temperature, activity and sleep
measure: Nutritional evaluation
time frame: 8 years old
description: Dietary assessment by food frequency questionnaire and by 3 day of dietary record
measure: Physical activity
time frame: 8 years old
description: questionnaires
measure: Physical Activity
time frame: 8 years old
description: Accelerometers will be used also to record activity of the subjects
arm group label: Control
description: Children at 8 years old born from healthy pregnancies
arm group label: GDM
description: Children at 8 years old born from mothers with gestational diabetes during pregnancy
Saliva, urine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 8 Years
maximum age: 9 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Elvira Larqué, Dr.
role: Principal Investigator
affiliation: Universidad de Murcia
last name: Cristina Campoy, MD
role: Principal Investigator
affiliation: Universidad de Granada
last name: Elvira Larqué, Dr
phone: 0034868884239
email: elvirada@um.es
last name: Cristina Campoy, MD
phone: 0034958240740
email: ccampoy@ugr.es
facility: 
status: Recruiting
contact: 
contact backup: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Universidad de Murcia
investigator full name: Elvira Larqué
investigator title: Professor
mesh term: Diabetes, Gestational
mesh term: Neurodevelopmental Disorders