<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/NCT03041129</url>
  </required_header>
  <id_info>
    <org_study_id>16-2399</org_study_id>
    <nct_id>NCT03041129</nct_id>
  </id_info>
  <brief_title>Post-Prandial Liver Glucose Metabolism in PCOS</brief_title>
  <acronym>PLUM</acronym>
  <official_title>Post-Prandial Liver Glucose Metabolism in Polycystic Ovarian Syndrome (PCOS) and Understanding Standard of Care Medications</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</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 measure if hepatic metabolism is upregulated in obese girls with PCOS&#xD;
      and hepatic steatosis (HS), compared to PCOS without HS and obese controls without HS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a cross-sectional study with 4 groups of youth. A 6 hour OSTT (Oral Sugar&#xD;
      Tolerance Test) with an oral U-C13 glycerol tracer will be paired with nuclear magnetic&#xD;
      resonance spectroscopy (NMR) isotopomer analysis of serum samples to describe flux through&#xD;
      the hepatic pentose phosphate pathway, TCA cycle and FAS pathways in girls with PCOS&#xD;
      receiving lifestyle only, metformin or oral contraceptive treatment, and obese girls with&#xD;
      regular menses receiving lifestyle therapy. Hepatic steatosis will be measured with MRI.&#xD;
&#xD;
      Please note that 3 study groups: PCOS on metformin, PCOS on oral contraceptive treatment, and&#xD;
      obese girls with regular menses were not funded in the study, so no participants were&#xD;
      enrolled in these 3 arms of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 14, 2017</start_date>
  <completion_date type="Actual">September 29, 2018</completion_date>
  <primary_completion_date type="Actual">August 29, 2018</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Hepatic fat fraction</measure>
    <time_frame>Within 4 months from Screening Visit</time_frame>
    <description>Amount of fat in the liver</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hepatic metabolism ratios</measure>
    <time_frame>Within 4 months from Screening Visit</time_frame>
    <description>Ratio of pentose phosphate pathway, TCA cycle and fatty acid synthesis metabolites following an OGTT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Whole Body Insulin Sensitivity</measure>
    <time_frame>Within 4 months from Screening Visit</time_frame>
    <description>Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep duration</measure>
    <time_frame>Within 4 months from Screening Visit</time_frame>
    <description>Sleep duration will be assessed using home actigraphy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep quality</measure>
    <time_frame>Within 4 months from Screening Visit</time_frame>
    <description>Apnea Hypopnea Index (AHI) will be measured using WatchPAT. In children and adolescents the scale that will be used is AHI&gt;5 is considered mild sleep apnea. The higher the AHI, indicates more severe sleep apnea.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool microbiome profile</measure>
    <time_frame>Within 4 months from Screening Visit</time_frame>
    <description>Stool microbiome profiles will be determined</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hepatic phosphate concentrations</measure>
    <time_frame>Within 4 months from Screening Visit</time_frame>
    <description>31 phosphorus spectroscopy will be utilized to measure hepatic phosphate concentrations</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">19</enrollment>
  <condition>Polycystic Ovarian Syndrome</condition>
  <condition>Obesity</condition>
  <condition>Hepatic Steatosis</condition>
  <arm_group>
    <arm_group_label>Untreated PCOS</arm_group_label>
    <description>PCOS per NIH criteria. Obese Lifestyle treatment only.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin PCOS-(Study arm not funded)</arm_group_label>
    <description>PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Oral Contraceptive PCOS-(Study arm not funded)</arm_group_label>
    <description>PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Obese Control group-(Study arm not funded)</arm_group_label>
    <description>Obese Regular menses at least 18 months post-menarche Females only</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>oral glucose tolerance test</intervention_name>
    <description>6 hours OGTT</description>
    <arm_group_label>Metformin PCOS-(Study arm not funded)</arm_group_label>
    <arm_group_label>Obese Control group-(Study arm not funded)</arm_group_label>
    <arm_group_label>Oral Contraceptive PCOS-(Study arm not funded)</arm_group_label>
    <arm_group_label>Untreated PCOS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MRI of liver</intervention_name>
    <description>MRI of the liver and use of DIXON method</description>
    <arm_group_label>Metformin PCOS-(Study arm not funded)</arm_group_label>
    <arm_group_label>Obese Control group-(Study arm not funded)</arm_group_label>
    <arm_group_label>Oral Contraceptive PCOS-(Study arm not funded)</arm_group_label>
    <arm_group_label>Untreated PCOS</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA for hepatic steatosis related genes&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Girls age 12-21. Obese &gt;90th percentile for BMI for age.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female&#xD;
&#xD;
          2. Ages 12-21&#xD;
&#xD;
          3. Sedentary- less than 2.5 hours of moderate (jogging, swimming etc) exercise a week.&#xD;
&#xD;
          4. BMI equal or greater than the 90th percentile for age and gender&#xD;
&#xD;
          5. For PCOS groups:&#xD;
&#xD;
               -  (NIH definition) irregular menstrual cycles at least 1.5 years after menarche,&#xD;
                  and&#xD;
&#xD;
               -  either clinical evidence of hyperandogenism, or&#xD;
&#xD;
               -  elevated Testosterone (above the norms for age/tanner stage) at time of&#xD;
                  screening, or documented prior to initiation of therapy for OCP and metformin&#xD;
                  groups.&#xD;
&#xD;
          6. For PCOS groups:&#xD;
&#xD;
               -  patients un-treated or currently treated with either Metformin 1500-2000 mg a&#xD;
                  day, or&#xD;
&#xD;
               -  oral contraception (30-35 mcg ethynyl estradiol a day) for at least 6 months,&#xD;
                  with &gt; 80% adherence confirmed via refill frequency from pharmacy.&#xD;
&#xD;
          7. For non-PCOS groups:&#xD;
&#xD;
               -  regular menstrual cycles at least 1.5 years after menarche, and&#xD;
&#xD;
               -  no clinical evidence of hyperandrogenism.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of medications known to affect insulin sensitivity:&#xD;
&#xD;
               -  oral glucocorticoids within 10 days,&#xD;
&#xD;
               -  atypical antipsychotics,&#xD;
&#xD;
               -  immunosuppressant agents,&#xD;
&#xD;
               -  HIV medications.&#xD;
&#xD;
               -  Nexplanon, Depo-Provera or Mirena progesterone only contraceptives.&#xD;
&#xD;
               -  Dermal patch or vaginal ring contraception methods.&#xD;
&#xD;
               -  For controls only: metformin or oral contraception.&#xD;
&#xD;
          2. Currently pregnant or breastfeeding women. Development of pregnancy during the study&#xD;
             period will necessitate withdrawal from the study.&#xD;
&#xD;
          3. Severe illness requiring hospitalization within 60 days&#xD;
&#xD;
          4. Diabetes, defined as Hemoglobin A1C &gt; 6.4%&#xD;
&#xD;
          5. BMI percentile less than the 90th percentile for age and sex.&#xD;
&#xD;
          6. Weight &gt;325 lbs or &lt;84 lbs.&#xD;
&#xD;
          7. Anemia, defined as Hemoglobin &lt; 10 mg/dL&#xD;
&#xD;
          8. Diagnosed major psychiatric or developmental disorder limiting informed consent&#xD;
&#xD;
          9. Implanted metal devices that are not compatible with MRI&#xD;
&#xD;
         10. Use of blood pressure medications&#xD;
&#xD;
         11. Known liver disease other than NAFLD or AST or ALT &gt;150 mg/mL&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Females only</gender_description>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melanie Cree-Green, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Anshutz Medical Campus/Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>February 20, 2020</last_update_submitted>
  <last_update_submitted_qc>February 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hepatic de novo lipogenesis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 6, 2022</submitted>
    <returned>February 6, 2023</returned>
    <submitted>August 15, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03041129
org study id: 16-2399
nct id: NCT03041129
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The Investigators will measure if hepatic metabolism is upregulated in obese girls with PCOS
      and hepatic steatosis (HS), compared to PCOS without HS and obese controls without HS.
This will be a cross-sectional study with 4 groups of youth. A 6 hour OSTT (Oral Sugar
      Tolerance Test) with an oral U-C13 glycerol tracer will be paired with nuclear magnetic
      resonance spectroscopy (NMR) isotopomer analysis of serum samples to describe flux through
      the hepatic pentose phosphate pathway, TCA cycle and FAS pathways in girls with PCOS
      receiving lifestyle only, metformin or oral contraceptive treatment, and obese girls with
      regular menses receiving lifestyle therapy. Hepatic steatosis will be measured with MRI.

      Please note that 3 study groups: PCOS on metformin, PCOS on oral contraceptive treatment, and
      obese girls with regular menses were not funded in the study, so no participants were
      enrolled in these 3 arms of the study.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Hepatic fat fraction
time frame: Within 4 months from Screening Visit
description: Amount of fat in the liver
measure: Hepatic metabolism ratios
time frame: Within 4 months from Screening Visit
description: Ratio of pentose phosphate pathway, TCA cycle and fatty acid synthesis metabolites following an OGTT
measure: Whole Body Insulin Sensitivity
time frame: Within 4 months from Screening Visit
description: Participants will undergo a 75 gram oral glucose tolerance test, and whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model.
measure: Sleep duration
time frame: Within 4 months from Screening Visit
description: Sleep duration will be assessed using home actigraphy
measure: Sleep quality
time frame: Within 4 months from Screening Visit
description: Apnea Hypopnea Index (AHI) will be measured using WatchPAT. In children and adolescents the scale that will be used is AHI>5 is considered mild sleep apnea. The higher the AHI, indicates more severe sleep apnea.
measure: Stool microbiome profile
time frame: Within 4 months from Screening Visit
description: Stool microbiome profiles will be determined
measure: Hepatic phosphate concentrations
time frame: Within 4 months from Screening Visit
description: 31 phosphorus spectroscopy will be utilized to measure hepatic phosphate concentrations
arm group label: Untreated PCOS
description: PCOS per NIH criteria. Obese Lifestyle treatment only.
arm group label: Metformin PCOS-(Study arm not funded)
description: PCOS per NIH criteria. Obese Taking 1500 mg of metformin or more per day for at least 6 months.
arm group label: Oral Contraceptive PCOS-(Study arm not funded)
description: PCOS per NIH criteria. Obese Taking 30 mcg of ethanyl estradiol or more per day for at least 6 months.
arm group label: Obese Control group-(Study arm not funded)
description: Obese Regular menses at least 18 months post-menarche Females only
intervention type: Diagnostic Test
intervention name: oral glucose tolerance test
description: 6 hours OGTT
arm group label: Metformin PCOS-(Study arm not funded)
arm group label: Obese Control group-(Study arm not funded)
arm group label: Oral Contraceptive PCOS-(Study arm not funded)
arm group label: Untreated PCOS
intervention type: Diagnostic Test
intervention name: MRI of liver
description: MRI of the liver and use of DIXON method
arm group label: Metformin PCOS-(Study arm not funded)
arm group label: Obese Control group-(Study arm not funded)
arm group label: Oral Contraceptive PCOS-(Study arm not funded)
arm group label: Untreated PCOS
DNA for hepatic steatosis related genes
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Females only
minimum age: 12 Years
maximum age: 21 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Melanie Cree-Green, MD, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Fatty Liver
mesh term: Syndrome
sharing ipd: No
submitted: May 6, 2022
returned: February 6, 2023
submitted: August 15, 2023