<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/NCT03816605</url>
  </required_header>
  <id_info>
    <org_study_id>FGF19</org_study_id>
    <nct_id>NCT03816605</nct_id>
  </id_info>
  <brief_title>FGF19 and the Expression of IRS-1 and GLUT-1 in Gestational Diabetes Mellitus</brief_title>
  <official_title>Effects of Fibroblast Growth Factors 19 on the Expression of Insulin Receptor Substrate-1/Glucose Transporter-1 in Trophoblast Cells Cultured in High Glucose</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital, Sun Yat-Sen University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First Affiliated Hospital, Sun Yat-Sen University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Insulin resistance plays a key role in the development of gestational diabetes mellitus(GDM).&#xD;
      As the largest endocrine organ and the transport intermediary of maternal-fetal nutrient and&#xD;
      a large of hormone and enzymes, placenta not only plays an important role in insulin&#xD;
      resistance, but also have a profound effect on fetal growth and development.&#xD;
&#xD;
      Insulin receptor substrate(IRS)-1, as a key signaling protein, plays vital role in the&#xD;
      downstream of insulin receptor signaling pathway. Many studies have suggested that the&#xD;
      central part of insulin resistance may be the insulin receptor substrate defect and the&#xD;
      abnormal expression of the gene or protein of IRS-1 is one of the molecular mechanisms of the&#xD;
      dysfunction of the insulin signaling pathway. The expression of IRS-1 and its tyrosine&#xD;
      phosphorylated protein decreased abnormally in placenta, skeletal muscle and adipose tissue&#xD;
      of GDM patients, which might be a significant cause to insulin resistance in GDM.&#xD;
&#xD;
      Besides, glucose transporter-1(GLUT-1), which may play a major role in the glucose&#xD;
      transporter in the placenta. The increase of blood glucose in patients with GDM has apparent&#xD;
      up-regulating effect on the expression of GLUT-1 in the placenta, which is associated the&#xD;
      development of offspring.&#xD;
&#xD;
      The investigators' previous study showed that FGF19 in serum, placenta and musculus rectus&#xD;
      abdominis was significantly decreased in patients with GDM, and was related to insulin&#xD;
      resistance. Thus, the investigators speculate that the abnormal expression of FGF19 may be&#xD;
      involved in the development of insulin resistance in GDM patients and disorder of&#xD;
      carbohydrate and lipid metabolism.&#xD;
&#xD;
      In the present study, the investigators will further investigate the effect of FGF19 on the&#xD;
      expression of IRS-1/GLUT-1 in cultured trophoblast cells of high glucose, and probe into the&#xD;
      effect of FGF19 on the insulin resistance and glucose transport.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Women who choose to terminate pregnancy because of maternal factors at the first and second&#xD;
      trimester, or delivered at term in the First Affiliated Hospital of Sun Yat-sen University&#xD;
      were enrolled in the study.&#xD;
&#xD;
      Samples for measurement were obtained from women undergoing induced abortion or caesarean&#xD;
      section. The villous trophoblast extracted from the placental villus were treated with&#xD;
      recombinant FGF19, high glucose medium or both recombinant FGF19 and high glucose medium or&#xD;
      neither. By the end of culture, mRNA and protein expression levels of IRS-1/GLUT-1 were&#xD;
      investigated with real-time quantitative polymerase chain reaction (qRT-PCR) and&#xD;
      western-blot, respectively. Clinical data were collected and analyzed.&#xD;
&#xD;
      Data were analyzed by SPSS20.0 database. The results were expressed as mean ± standard&#xD;
      deviations, median or rate. Differences between groups were assessed by Student's unpaired t&#xD;
      test, Mann-Whitney U test, or Chi-square test as appropriate. P values of &lt;0.05 were&#xD;
      considered significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</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>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Expression of IRS-1 and GLUT-1 in different group</measure>
    <time_frame>six months</time_frame>
    <description>concentration of IRS-1 and GLUT-1 in mmol/l</description>
  </primary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">36</enrollment>
  <condition>Gestational Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <description>Cells were cultured in the basic medium containing 2× penicillin and streptomycin antibody.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Recombinant FGF19</arm_group_label>
    <description>Cells were cultured in the basic medium with recombinant FGF19 at concentration of 100ng/ml.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High-glucose</arm_group_label>
    <description>Cells were cultured in the high-glucose medium at concentration of 25mM.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FGF19 and HG</arm_group_label>
    <description>Cells were cultured in the medium with both recombinant FGF19 and high-glucose.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        University hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women who choose to terminate pregnancy because of maternal factors in the First&#xD;
             Affiliated Hospital of Sun Yat-sen University at the 6-10 weeks of gestation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Younger than 18 years old;&#xD;
&#xD;
          -  Older than 40 years old;&#xD;
&#xD;
          -  Diagnosed DM before pregnancy;&#xD;
&#xD;
          -  Complicated with other diseases such as GDM, insulin resistance, obesity and related&#xD;
             endocrine diseases, etc.;&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zilian Wang, M.D.,PhD</last_name>
    <role>Study Director</role>
    <affiliation>O&amp;G Department of the 1st affiliated hospital of Sun Yat-sen University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Obstetrics and Gynechology Department of the 1st affiliated hospital of Sun Yat-sen University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>January 23, 2019</last_update_submitted>
  <last_update_submitted_qc>January 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>First Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
    <investigator_full_name>Dongyu Wang</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>GDM</keyword>
  <keyword>IRS-1</keyword>
  <keyword>GLUT-1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</mesh_term>
    <mesh_term>Diabetes Mellitus</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/NCT03816605
org study id: FGF19
nct id: NCT03816605
lead sponsor: 
has dmc: Yes
Insulin resistance plays a key role in the development of gestational diabetes mellitus(GDM).
      As the largest endocrine organ and the transport intermediary of maternal-fetal nutrient and
      a large of hormone and enzymes, placenta not only plays an important role in insulin
      resistance, but also have a profound effect on fetal growth and development.

      Insulin receptor substrate(IRS)-1, as a key signaling protein, plays vital role in the
      downstream of insulin receptor signaling pathway. Many studies have suggested that the
      central part of insulin resistance may be the insulin receptor substrate defect and the
      abnormal expression of the gene or protein of IRS-1 is one of the molecular mechanisms of the
      dysfunction of the insulin signaling pathway. The expression of IRS-1 and its tyrosine
      phosphorylated protein decreased abnormally in placenta, skeletal muscle and adipose tissue
      of GDM patients, which might be a significant cause to insulin resistance in GDM.

      Besides, glucose transporter-1(GLUT-1), which may play a major role in the glucose
      transporter in the placenta. The increase of blood glucose in patients with GDM has apparent
      up-regulating effect on the expression of GLUT-1 in the placenta, which is associated the
      development of offspring.

      The investigators' previous study showed that FGF19 in serum, placenta and musculus rectus
      abdominis was significantly decreased in patients with GDM, and was related to insulin
      resistance. Thus, the investigators speculate that the abnormal expression of FGF19 may be
      involved in the development of insulin resistance in GDM patients and disorder of
      carbohydrate and lipid metabolism.

      In the present study, the investigators will further investigate the effect of FGF19 on the
      expression of IRS-1/GLUT-1 in cultured trophoblast cells of high glucose, and probe into the
      effect of FGF19 on the insulin resistance and glucose transport.
Women who choose to terminate pregnancy because of maternal factors at the first and second
      trimester, or delivered at term in the First Affiliated Hospital of Sun Yat-sen University
      were enrolled in the study.

      Samples for measurement were obtained from women undergoing induced abortion or caesarean
      section. The villous trophoblast extracted from the placental villus were treated with
      recombinant FGF19, high glucose medium or both recombinant FGF19 and high glucose medium or
      neither. By the end of culture, mRNA and protein expression levels of IRS-1/GLUT-1 were
      investigated with real-time quantitative polymerase chain reaction (qRT-PCR) and
      western-blot, respectively. Clinical data were collected and analyzed.

      Data were analyzed by SPSS20.0 database. The results were expressed as mean ± standard
      deviations, median or rate. Differences between groups were assessed by Student's unpaired t
      test, Mann-Whitney U test, or Chi-square test as appropriate. P values of <0.05 were
      considered significant.
observational model: Case-Control
time perspective: Retrospective
measure: Expression of IRS-1 and GLUT-1 in different group
time frame: six months
description: concentration of IRS-1 and GLUT-1 in mmol/l
arm group label: control
description: Cells were cultured in the basic medium containing 2× penicillin and streptomycin antibody.
arm group label: Recombinant FGF19
description: Cells were cultured in the basic medium with recombinant FGF19 at concentration of 100ng/ml.
arm group label: High-glucose
description: Cells were cultured in the high-glucose medium at concentration of 25mM.
arm group label: FGF19 and HG
description: Cells were cultured in the medium with both recombinant FGF19 and high-glucose.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Zilian Wang, M.D.,PhD
role: Study Director
affiliation: O&G Department of the 1st affiliated hospital of Sun Yat-sen University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: First Affiliated Hospital, Sun Yat-Sen University
investigator full name: Dongyu Wang
investigator title: Principal Investigator
mesh term: Diabetes, Gestational
mesh term: Diabetes Mellitus