<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/NCT02198417</url>
  </required_header>
  <id_info>
    <org_study_id>2014P000911</org_study_id>
    <secondary_id>R01HD065029</secondary_id>
    <nct_id>NCT02198417</nct_id>
  </id_info>
  <brief_title>Metformin Treatment in Polycystic Ovary Syndrome (PCOS)</brief_title>
  <official_title>Effects of Metformin on Mitochondrial Function in Polycystic Ovary Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      PCOS occurs when a woman does not release an egg regularly each month, causing her periods to&#xD;
      be irregular. Women with PCOS can also have increased hair growth on the face and body, acne,&#xD;
      head balding, infertility, pre-diabetes, and diabetes. PCOS is commonly treated with oral&#xD;
      contraceptive pills (also known as the birth control pills). Sometimes, a medication called&#xD;
      metformin is also used to treat PCOS, especially if a woman has evidence of insulin&#xD;
      resistance or if fertility is desired. Unfortunately, metformin works in only some women with&#xD;
      PCOS. The mechanism through which metformin works in PCOS is not clear and it difficult to&#xD;
      predict who will benefit from metformin treatment and who will not.&#xD;
&#xD;
      The investigators are doing this research study to look at how the medication metformin&#xD;
      affects the cells in the body of patients with PCOS. Specifically, the investigators will&#xD;
      look at how metformin affects the mitochondria. Mitochondria are the part of cells that&#xD;
      produce fuel (energy) for other cells and play a role in metabolism. The investigators would&#xD;
      like to see whether there is a relationship between mitochondrial activity and symptoms of&#xD;
      polycystic ovary syndrome (PCOS) before and after treatment with metformin. They would also&#xD;
      like to study whether genes affect the response to metformin in women with PCOS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Women who are eligible to enroll in this study will be treated with the medication metformin&#xD;
      for 12 weeks. Before and after treatment with metformin, the following will be assessed:&#xD;
&#xD;
        -  Weight, blood pressure, waist circumference&#xD;
&#xD;
        -  Lipids (cholesterol)&#xD;
&#xD;
        -  Hormone levels (including testosterone and other androgens)&#xD;
&#xD;
        -  IV glucose tolerance test (to assess for early evidence of insulin resistance)&#xD;
&#xD;
        -  Effect of metformin on muscle mitochondria (this will involve one MRI scan and one&#xD;
           muscle biopsy each before and after treatment with metformin)&#xD;
&#xD;
      Ovulation will be closely monitored at least twice a month with pelvic ultrasounds and blood&#xD;
      tests for estrogen and progesterone levels.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">September 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Muscle Metabolism/Mitochondrial Function</measure>
    <time_frame>3 months</time_frame>
    <description>The change in mitochondrial activity before and after metformin treatment will be analyzed in relationship to the clinical response to 3 months of metformin treatment (i.e., clinical response to metformin = changes in glucose metabolism, hormone levels, and ovulation response)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Genetic risk variants affecting mitochondrial function/metabolism</measure>
    <time_frame>3 months</time_frame>
    <description>Blood will be analyzed for differences in genes between patients and its relationship to mitochondrial function.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Metformin ER 1500 mg per day treatment for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin ER</intervention_name>
    <description>Treatment with metformin ER for 12 weeks</description>
    <arm_group_label>Metformin</arm_group_label>
    <other_name>Glucophage</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Polycystic ovary syndrome&#xD;
&#xD;
          -  No hormonal or antidiabetic medications for 1 month&#xD;
&#xD;
          -  Good general health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoker&#xD;
&#xD;
          -  Acute infection or chronic disease&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Pregnant or trying to get pregnant over next half year&#xD;
&#xD;
          -  Bleeding disorders&#xD;
&#xD;
          -  Any metal or foreign implants (e.g., aneurysm clips, ear implants, heart pacemakers or&#xD;
             defibrillators)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Corrine Welt, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <reference>
    <citation>Pau CT, Keefe C, Duran J, Welt CK. Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label, interventional study. J Clin Endocrinol Metab. 2014 May;99(5):1870-8. doi: 10.1210/jc.2013-4021. Epub 2014 Feb 25.</citation>
    <PMID>24606093</PMID>
  </reference>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>August 14, 2018</last_update_submitted>
  <last_update_submitted_qc>August 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Corrine Welt</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Polycystic Ovary Syndrome</keyword>
  <keyword>PCOS</keyword>
  <keyword>Acne</keyword>
  <keyword>Infertility</keyword>
  <keyword>Irregular menses</keyword>
  <keyword>Irregular period</keyword>
  <keyword>Mitochondria</keyword>
  <keyword>Metabolism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_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/NCT02198417
org study id: 2014P000911
secondary id: R01HD065029
nct id: NCT02198417
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
PCOS occurs when a woman does not release an egg regularly each month, causing her periods to
      be irregular. Women with PCOS can also have increased hair growth on the face and body, acne,
      head balding, infertility, pre-diabetes, and diabetes. PCOS is commonly treated with oral
      contraceptive pills (also known as the birth control pills). Sometimes, a medication called
      metformin is also used to treat PCOS, especially if a woman has evidence of insulin
      resistance or if fertility is desired. Unfortunately, metformin works in only some women with
      PCOS. The mechanism through which metformin works in PCOS is not clear and it difficult to
      predict who will benefit from metformin treatment and who will not.

      The investigators are doing this research study to look at how the medication metformin
      affects the cells in the body of patients with PCOS. Specifically, the investigators will
      look at how metformin affects the mitochondria. Mitochondria are the part of cells that
      produce fuel (energy) for other cells and play a role in metabolism. The investigators would
      like to see whether there is a relationship between mitochondrial activity and symptoms of
      polycystic ovary syndrome (PCOS) before and after treatment with metformin. They would also
      like to study whether genes affect the response to metformin in women with PCOS.
Women who are eligible to enroll in this study will be treated with the medication metformin
      for 12 weeks. Before and after treatment with metformin, the following will be assessed:

        -  Weight, blood pressure, waist circumference

        -  Lipids (cholesterol)

        -  Hormone levels (including testosterone and other androgens)

        -  IV glucose tolerance test (to assess for early evidence of insulin resistance)

        -  Effect of metformin on muscle mitochondria (this will involve one MRI scan and one
           muscle biopsy each before and after treatment with metformin)

      Ovulation will be closely monitored at least twice a month with pelvic ultrasounds and blood
      tests for estrogen and progesterone levels.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Muscle Metabolism/Mitochondrial Function
time frame: 3 months
description: The change in mitochondrial activity before and after metformin treatment will be analyzed in relationship to the clinical response to 3 months of metformin treatment (i.e., clinical response to metformin = changes in glucose metabolism, hormone levels, and ovulation response)
measure: Genetic risk variants affecting mitochondrial function/metabolism
time frame: 3 months
description: Blood will be analyzed for differences in genes between patients and its relationship to mitochondrial function.
arm group label: Metformin
arm group type: Experimental
description: Metformin ER 1500 mg per day treatment for 12 weeks
intervention type: Drug
intervention name: Metformin ER
description: Treatment with metformin ER for 12 weeks
arm group label: Metformin
other name: Glucophage
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Corrine Welt, M.D.
role: Principal Investigator
affiliation: Massachusetts General Hospital
country: United States
citation: Pau CT, Keefe C, Duran J, Welt CK. Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label, interventional study. J Clin Endocrinol Metab. 2014 May;99(5):1870-8. doi: 10.1210/jc.2013-4021. Epub 2014 Feb 25.
PMID: 24606093
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Corrine Welt
investigator title: Professor of Medicine
mesh term: Polycystic Ovary Syndrome
mesh term: Syndrome
mesh term: Metformin