<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/NCT01697566</url>
  </required_header>
  <id_info>
    <org_study_id>2011-0739</org_study_id>
    <secondary_id>5P50CA098258</secondary_id>
    <secondary_id>NCI-2013-00834</secondary_id>
    <nct_id>NCT01697566</nct_id>
  </id_info>
  <brief_title>An Endometrial Cancer Chemoprevention Study of Metformin</brief_title>
  <official_title>An Endometrial Cancer Chemoprevention Study of Metformin Versus No Treatment in Women With a Body Mass Index (BMI) &gt;/= 30 kg.m2 and Hyperinsulinemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson Cancer Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this clinical research study is to learn about the effects of metformin and/or a&#xD;
      program called &quot;lifestyle intervention&quot; on the endometrium (inner lining of the uterus) in&#xD;
      post-menopausal women who are also obese (both are risk factors for endometrial cancer).&#xD;
      Researchers also want to learn how insulin levels will be affected by metformin, diet and/or&#xD;
      exercise.&#xD;
&#xD;
      Metformin is designed to treat both diabetes and insulin resistance. Insulin resistance is a&#xD;
      condition in which the body makes insulin but does not use it properly. It is often referred&#xD;
      to as &quot;pre-diabetes&quot;. Many people with insulin resistance have high levels of both sugar and&#xD;
      insulin in their blood at the same time, which have been reported in patients with&#xD;
      endometrial cancer.&#xD;
&#xD;
      In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks&#xD;
      like the study drug but is not designed to treat any disease or illness. It is designed to be&#xD;
      compared with a study drug to learn if the study drug has any real effect.&#xD;
&#xD;
      Lifestyle intervention is made up of a series of in-person sessions where you meet with a&#xD;
      coach to discuss strategies for losing weight and ways to increase physical activity. It also&#xD;
      consists of materials designed to help you lose weight and will offer opportunities for&#xD;
      supervised exercise.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Groups:&#xD;
&#xD;
      If you are found to be eligible to take part in this study, you will be randomly assigned (as&#xD;
      in the roll of dice) to 1 of 4 study groups:&#xD;
&#xD;
        -  Metformin only.&#xD;
&#xD;
        -  Placebo and lifestyle intervention.&#xD;
&#xD;
        -  Metformin and lifestyle intervention.&#xD;
&#xD;
        -  Placebo only.&#xD;
&#xD;
      Neither you nor the study staff will know if you are receiving metformin or placebo. However,&#xD;
      if needed for your safety, the study staff will be able to find out what you are receiving.&#xD;
&#xD;
      In the first month you will gradually increase the dose of metformin/placebo by mouth as&#xD;
      listed below:&#xD;
&#xD;
        -  Week 1: One capsule each day&#xD;
&#xD;
        -  Week 2: One capsule 2 times each day&#xD;
&#xD;
        -  Week 3: One capsule 3 times each day&#xD;
&#xD;
        -  Week 4: Two capsules 2 times each day&#xD;
&#xD;
      After week 4, you will continue to take 2 capsules of metformin/placebo 2 times each day.&#xD;
&#xD;
      If you are receiving the lifestyle intervention, you will have 16 lifestyle intervention&#xD;
      sessions over 4 months. At each of these sessions, you will discuss methods for managing your&#xD;
      weight. You will receive print materials and worksheets, measuring utensils, and a food&#xD;
      scale. You will be instructed how to use each of these materials and how often to use them&#xD;
      during the study. You will also be provided with opportunities for supervised exercise (such&#xD;
      as group exercise class and group walks).&#xD;
&#xD;
      If you are traveling during a scheduled session, it can be performed over the telephone. Each&#xD;
      call should last about 30 minutes, during which you will discuss the same goals and&#xD;
      information that you would discuss in the in-person sessions.&#xD;
&#xD;
      Study Visits:&#xD;
&#xD;
      Before you can begin receiving the study drug/placebo:&#xD;
&#xD;
        -  At the second screening visit , you will have a dual energy x-ray absorptiometry (DEXA)&#xD;
           scan to measure your body composition. The scan requires you to lie still on a table for&#xD;
           about 8-10 minutes while a low-energy x-ray takes an image that allows the study staff&#xD;
           to get an image of your body fat density.&#xD;
&#xD;
        -  You will be given an accelerometer (a small, portable device that measures your physical&#xD;
           activity) and be taught how to use it at the first Screening Visit. You will wear the&#xD;
           accelerometer at all times while you are awake for 7 days. At the second Screening&#xD;
           Visit, you will return the accelerometer at an intervention session. If you are not able&#xD;
           to return it at the second visit then you will mail it back to the study staff in a&#xD;
           pre-paid envelope. You will receive the accelerometer again at Month 4 and wear it for&#xD;
           another 7 days.&#xD;
&#xD;
        -  You will receive a study diary in which you will record any and all exercise you perform&#xD;
           each day while you are on study. It should take about 5 minutes to complete each time.&#xD;
&#xD;
        -  You will complete questionnaires about diet and exercise. These questionnaires should&#xD;
           take about 30-40 minutes to complete.&#xD;
&#xD;
        -  You will also be taught to complete a questionnaire on the internet to record the food&#xD;
           you eat in a 24 hour period. You will do this 3 times over a 2 week period. The first&#xD;
           time, you will complete it at the clinic. The study staff will call and remind you to&#xD;
           complete the questionnaire the other 2 times. Each time you complete this questionnaire,&#xD;
           it should take about 40 minutes.&#xD;
&#xD;
      At Month 1, all participants will return for a study visit. The following tests and&#xD;
      procedures will be performed:&#xD;
&#xD;
        -  Blood (about 2 teaspoons) will be drawn for routine tests. If this blood draw shows that&#xD;
           your liver or kidney function is abnormal, you will need to return for an additional&#xD;
           blood °draw at Month 2.&#xD;
&#xD;
        -  If you are having symptoms that you would describe as moderate or worse, you will have a&#xD;
           non-pelvic physical exam including measurement of your vital signs and any unreported&#xD;
           symptoms you may be having.&#xD;
&#xD;
      At each month, you will be asked about any symptom(s) that you may have to learn if it is&#xD;
      related to the study. If you are called, this phone call should last about 5 minutes. If you&#xD;
      are asked in a in-person visit, the visit can last up to an hour.&#xD;
&#xD;
      Length of Study:&#xD;
&#xD;
      You will receive the study drug/placebo and/or lifestyle intervention for up to 4 months. You&#xD;
      will be taken off study if you have intolerable side effects or if you develop endometrial&#xD;
      cancer or hyperplasia during the study. Your participation in the study will be over after&#xD;
      the end-of-study visit.&#xD;
&#xD;
      Post-Treatment Visit:&#xD;
&#xD;
      At the end of the 4th month, you will have a post-treatment visit. You will repeat all&#xD;
      procedures performed in the first and second visit:&#xD;
&#xD;
        -  Your height, weight, waist, and hip circumference will be measured.&#xD;
&#xD;
        -  You will have a DEXA scan.&#xD;
&#xD;
        -  You will complete the questionnaires about food, diet, and exercise.&#xD;
&#xD;
        -  You will be given a questionnaire about your satisfaction (based on the intervention) to&#xD;
           complete and return at this visit. This questionnaire will take up to an hour to&#xD;
           complete.&#xD;
&#xD;
        -  You will have an endometrial biopsy.&#xD;
&#xD;
        -  Blood (about 8 tablespoons) will be drawn for routine tests and for biomarker testing.&#xD;
           You will have to fast (not eat or drink anything except water) for 12 hours before this&#xD;
           blood draw.&#xD;
&#xD;
        -  You will complete the questionnaire on the internet to record the food you eat in a 24&#xD;
           hour period. You will do this 3 times over a 2 week period. The first time, you will&#xD;
           complete it at the clinic. The study staff will call and remind you to complete the&#xD;
           questionnaire the other 2 times. Each time you complete this questionnaire, it should&#xD;
           take about 40 minutes.&#xD;
&#xD;
      Follow-Up:&#xD;
&#xD;
      About 1 year after the screening visits (+/- 1 month), the following tests and procedures&#xD;
      will be performed:&#xD;
&#xD;
        -  Your height, weight, waist, and hip circumference will be measured.&#xD;
&#xD;
        -  You will have a DEXA scan.&#xD;
&#xD;
        -  Blood (about 8 tablespoons) will be drawn for routine tests and for biomarker testing.&#xD;
           °You will have to fast (not eat or drink anything except water) for 12 hours before this&#xD;
           blood draw.&#xD;
&#xD;
        -  You will wear the accelerometer for 7 days.&#xD;
&#xD;
        -  You will complete questionnaires about food, diet, and exercise.&#xD;
&#xD;
        -  You will complete the questionnaire on the internet to record the food you eat in a 24&#xD;
           hour period. You will do this 3 times over a 2 week period. The first time, you will&#xD;
           complete it at the clinic. The study staff will call and remind you to complete the&#xD;
           questionnaire the other 2 times. Each time you complete this questionnaire, it should&#xD;
           take about 40 minutes.&#xD;
&#xD;
      This is an investigational study. Metformin is FDA approved and commercially available for&#xD;
      the treatment of diabetes and insulin resistance.&#xD;
&#xD;
      Up to 100 patients will take part in this study. All will be enrolled at MD Anderson Cancer&#xD;
      Center.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 2, 2013</start_date>
  <completion_date type="Anticipated">May 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">May 30, 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effect of Metformin and/or Lifestyle Intervention on Biomarkers.</measure>
    <time_frame>4 months</time_frame>
    <description>Differences in Ki-67 and other biomarkers analyzed using a 2x2 ANOVA. Other biomarkers examined include a) a panel of genes relevant to estrogen dependent endometrial proliferation, hyperplasia and cancer using Q-PCR, b) biomarkers specific to the effect of metformin treatment (phospho-AMPKa, phospho-ACC, phospho-mTOR and phospho-S6 ribosomal protein and c) potential biomarkers of modulation of insulin sensitivity on the human endometrial proteome using reverse phase protein arrays (RPPA).</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Gynecology</condition>
  <arm_group>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants gradually increase the dose of metformin by mouth as listed below:&#xD;
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day&#xD;
After week 4, participant continues to take 2 capsules of metformin 2 times each day.&#xD;
Each capsule is 425 mg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + Lifestyle Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin + Lifestyle Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants gradually increase the dose of metformin by mouth as listed below:&#xD;
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day&#xD;
After week 4, participant continues to take 2 capsules of metformin 2 times each day.&#xD;
Each capsule is 425 mg.&#xD;
Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo taken by mouth twice daily for 4, 30 day cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Participants gradually increase the dose of metformin by mouth as listed below:&#xD;
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day&#xD;
After week 4, participant continues to take 2 capsules of metformin 2 times each day.&#xD;
Each capsule is 425 mg.</description>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_label>Metformin + Lifestyle Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo taken by mouth twice daily for 4, 30 day cycles.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Placebo + Lifestyle Intervention</arm_group_label>
    <other_name>sugar pill</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endometrial Biopsy</intervention_name>
    <description>Endometrial biopsies obtained at baseline and after 4 months.</description>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_label>Metformin + Lifestyle Intervention</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Placebo + Lifestyle Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Lifestyle Intervention</intervention_name>
    <description>Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.</description>
    <arm_group_label>Metformin + Lifestyle Intervention</arm_group_label>
    <arm_group_label>Placebo + Lifestyle Intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <description>Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.</description>
    <arm_group_label>Metformin</arm_group_label>
    <arm_group_label>Metformin + Lifestyle Intervention</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Placebo + Lifestyle Intervention</arm_group_label>
    <other_name>surveys</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. For this study, only women will be enrolled.&#xD;
&#xD;
          2. Body Mass Index (BMI) &gt; or = 30 kg/m2&#xD;
&#xD;
          3. Not frankly diabetic, as measured by a fasting blood glucose &lt;/=126 mg/dL.&#xD;
&#xD;
          4. Demonstrate hyperinsulinemia with a QUICK I value &lt;/= 0.357.&#xD;
&#xD;
          5. Age &gt;/= 50 and &lt;/= 65&#xD;
&#xD;
          6. Zubrod Performance Scale 0-1&#xD;
&#xD;
          7. Hemoglobin &gt;/= 10 g/dl&#xD;
&#xD;
          8. TSH 0.27 - 4.20 µlU/mL&#xD;
&#xD;
          9. Menopause as defined as no menses for 1 year and/or FSH &gt;/= 25.8 mIU/ml&#xD;
&#xD;
         10. Must be able to read, write, and speak English.&#xD;
&#xD;
         11. Must have a Primary Care Provider (PCP).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior hysterectomy or endometrial ablation&#xD;
&#xD;
          2. ALT &gt;/r = 2.0x Upper Limit of Normal (ULN)&#xD;
&#xD;
          3. Serum creatinine &gt; /= 1.4 mg/dl&#xD;
&#xD;
          4. Triglycerides (fasting) &gt;/ = 400&#xD;
&#xD;
          5. Known inability to participate in the ongoing appointments for the four months of the&#xD;
             study and scheduled follow-up tests.&#xD;
&#xD;
          6. Significant medical or psychiatric history which would make the participant a poor&#xD;
             protocol candidate, in the opinion of the principal investigator, for any aspect of&#xD;
             study participation including metformin, unsupervised exercise program or dietary&#xD;
             behavior change.&#xD;
&#xD;
          7. Participant reported history of congestive heart failure&#xD;
&#xD;
          8. Prior treatment with Metformin&#xD;
&#xD;
          9. Currently being treated for diabetes or meeting criteria for new diagnosis of&#xD;
             diabetes.&#xD;
&#xD;
         10. Known allergy to Metformin or other biguanide (Proguanil).&#xD;
&#xD;
         11. Use of Aromatase Inhibitors, GNRH-agonists i.e.Lupron, Zoladex within the last 6&#xD;
             months&#xD;
&#xD;
         12. Use of SERMS (selective estrogen receptor modulators) in the past 6 months, including&#xD;
             Tamoxifen and Raloxifene&#xD;
&#xD;
         13. Hormone replacement therapy within the last 6 months&#xD;
&#xD;
         14. Women who have been treated with chemotherapy for prior malignant disease or currently&#xD;
             have an untreated malignancy other than non-melanoma skin cancer&#xD;
&#xD;
         15. Patients who have had prior radiation to the pelvis&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karen H. Lu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>University of Texas MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <last_update_submitted>September 15, 2023</last_update_submitted>
  <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gynecology</keyword>
  <keyword>Endometrial Cancer Chemoprevention</keyword>
  <keyword>Obese</keyword>
  <keyword>Body Mass Index (BMI) &gt;/= 35 kg.m2</keyword>
  <keyword>Post-menopausal</keyword>
  <keyword>Hyperinsulinemia</keyword>
  <keyword>Metformin</keyword>
  <keyword>Placebo</keyword>
  <keyword>Sugar pill</keyword>
  <keyword>Lifestyle intervention</keyword>
  <keyword>Diet</keyword>
  <keyword>Exercise</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</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/NCT01697566
org study id: 2011-0739
secondary id: 5P50CA098258
secondary id: NCI-2013-00834
nct id: NCT01697566
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The goal of this clinical research study is to learn about the effects of metformin and/or a
      program called "lifestyle intervention" on the endometrium (inner lining of the uterus) in
      post-menopausal women who are also obese (both are risk factors for endometrial cancer).
      Researchers also want to learn how insulin levels will be affected by metformin, diet and/or
      exercise.

      Metformin is designed to treat both diabetes and insulin resistance. Insulin resistance is a
      condition in which the body makes insulin but does not use it properly. It is often referred
      to as "pre-diabetes". Many people with insulin resistance have high levels of both sugar and
      insulin in their blood at the same time, which have been reported in patients with
      endometrial cancer.

      In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks
      like the study drug but is not designed to treat any disease or illness. It is designed to be
      compared with a study drug to learn if the study drug has any real effect.

      Lifestyle intervention is made up of a series of in-person sessions where you meet with a
      coach to discuss strategies for losing weight and ways to increase physical activity. It also
      consists of materials designed to help you lose weight and will offer opportunities for
      supervised exercise.
Study Groups:

      If you are found to be eligible to take part in this study, you will be randomly assigned (as
      in the roll of dice) to 1 of 4 study groups:

        -  Metformin only.

        -  Placebo and lifestyle intervention.

        -  Metformin and lifestyle intervention.

        -  Placebo only.

      Neither you nor the study staff will know if you are receiving metformin or placebo. However,
      if needed for your safety, the study staff will be able to find out what you are receiving.

      In the first month you will gradually increase the dose of metformin/placebo by mouth as
      listed below:

        -  Week 1: One capsule each day

        -  Week 2: One capsule 2 times each day

        -  Week 3: One capsule 3 times each day

        -  Week 4: Two capsules 2 times each day

      After week 4, you will continue to take 2 capsules of metformin/placebo 2 times each day.

      If you are receiving the lifestyle intervention, you will have 16 lifestyle intervention
      sessions over 4 months. At each of these sessions, you will discuss methods for managing your
      weight. You will receive print materials and worksheets, measuring utensils, and a food
      scale. You will be instructed how to use each of these materials and how often to use them
      during the study. You will also be provided with opportunities for supervised exercise (such
      as group exercise class and group walks).

      If you are traveling during a scheduled session, it can be performed over the telephone. Each
      call should last about 30 minutes, during which you will discuss the same goals and
      information that you would discuss in the in-person sessions.

      Study Visits:

      Before you can begin receiving the study drug/placebo:

        -  At the second screening visit , you will have a dual energy x-ray absorptiometry (DEXA)
           scan to measure your body composition. The scan requires you to lie still on a table for
           about 8-10 minutes while a low-energy x-ray takes an image that allows the study staff
           to get an image of your body fat density.

        -  You will be given an accelerometer (a small, portable device that measures your physical
           activity) and be taught how to use it at the first Screening Visit. You will wear the
           accelerometer at all times while you are awake for 7 days. At the second Screening
           Visit, you will return the accelerometer at an intervention session. If you are not able
           to return it at the second visit then you will mail it back to the study staff in a
           pre-paid envelope. You will receive the accelerometer again at Month 4 and wear it for
           another 7 days.

        -  You will receive a study diary in which you will record any and all exercise you perform
           each day while you are on study. It should take about 5 minutes to complete each time.

        -  You will complete questionnaires about diet and exercise. These questionnaires should
           take about 30-40 minutes to complete.

        -  You will also be taught to complete a questionnaire on the internet to record the food
           you eat in a 24 hour period. You will do this 3 times over a 2 week period. The first
           time, you will complete it at the clinic. The study staff will call and remind you to
           complete the questionnaire the other 2 times. Each time you complete this questionnaire,
           it should take about 40 minutes.

      At Month 1, all participants will return for a study visit. The following tests and
      procedures will be performed:

        -  Blood (about 2 teaspoons) will be drawn for routine tests. If this blood draw shows that
           your liver or kidney function is abnormal, you will need to return for an additional
           blood °draw at Month 2.

        -  If you are having symptoms that you would describe as moderate or worse, you will have a
           non-pelvic physical exam including measurement of your vital signs and any unreported
           symptoms you may be having.

      At each month, you will be asked about any symptom(s) that you may have to learn if it is
      related to the study. If you are called, this phone call should last about 5 minutes. If you
      are asked in a in-person visit, the visit can last up to an hour.

      Length of Study:

      You will receive the study drug/placebo and/or lifestyle intervention for up to 4 months. You
      will be taken off study if you have intolerable side effects or if you develop endometrial
      cancer or hyperplasia during the study. Your participation in the study will be over after
      the end-of-study visit.

      Post-Treatment Visit:

      At the end of the 4th month, you will have a post-treatment visit. You will repeat all
      procedures performed in the first and second visit:

        -  Your height, weight, waist, and hip circumference will be measured.

        -  You will have a DEXA scan.

        -  You will complete the questionnaires about food, diet, and exercise.

        -  You will be given a questionnaire about your satisfaction (based on the intervention) to
           complete and return at this visit. This questionnaire will take up to an hour to
           complete.

        -  You will have an endometrial biopsy.

        -  Blood (about 8 tablespoons) will be drawn for routine tests and for biomarker testing.
           You will have to fast (not eat or drink anything except water) for 12 hours before this
           blood draw.

        -  You will complete the questionnaire on the internet to record the food you eat in a 24
           hour period. You will do this 3 times over a 2 week period. The first time, you will
           complete it at the clinic. The study staff will call and remind you to complete the
           questionnaire the other 2 times. Each time you complete this questionnaire, it should
           take about 40 minutes.

      Follow-Up:

      About 1 year after the screening visits (+/- 1 month), the following tests and procedures
      will be performed:

        -  Your height, weight, waist, and hip circumference will be measured.

        -  You will have a DEXA scan.

        -  Blood (about 8 tablespoons) will be drawn for routine tests and for biomarker testing.
           °You will have to fast (not eat or drink anything except water) for 12 hours before this
           blood draw.

        -  You will wear the accelerometer for 7 days.

        -  You will complete questionnaires about food, diet, and exercise.

        -  You will complete the questionnaire on the internet to record the food you eat in a 24
           hour period. You will do this 3 times over a 2 week period. The first time, you will
           complete it at the clinic. The study staff will call and remind you to complete the
           questionnaire the other 2 times. Each time you complete this questionnaire, it should
           take about 40 minutes.

      This is an investigational study. Metformin is FDA approved and commercially available for
      the treatment of diabetes and insulin resistance.

      Up to 100 patients will take part in this study. All will be enrolled at MD Anderson Cancer
      Center.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Effect of Metformin and/or Lifestyle Intervention on Biomarkers.
time frame: 4 months
description: Differences in Ki-67 and other biomarkers analyzed using a 2x2 ANOVA. Other biomarkers examined include a) a panel of genes relevant to estrogen dependent endometrial proliferation, hyperplasia and cancer using Q-PCR, b) biomarkers specific to the effect of metformin treatment (phospho-AMPKa, phospho-ACC, phospho-mTOR and phospho-S6 ribosomal protein and c) potential biomarkers of modulation of insulin sensitivity on the human endometrial proteome using reverse phase protein arrays (RPPA).
arm group label: Metformin
arm group type: Experimental
description: Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
arm group label: Placebo + Lifestyle Intervention
arm group type: Experimental
description: Placebo taken by mouth twice daily for 4, 30 day cycles. Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
arm group label: Metformin + Lifestyle Intervention
arm group type: Experimental
description: Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo taken by mouth twice daily for 4, 30 day cycles.
intervention type: Drug
intervention name: Metformin
description: Participants gradually increase the dose of metformin by mouth as listed below:
Week 1: One capsule each day Week 2: One capsule 2 times each day Week 3: One capsule 3 times each day Week 4: Two capsules 2 times each day
After week 4, participant continues to take 2 capsules of metformin 2 times each day.
Each capsule is 425 mg.
arm group label: Metformin
arm group label: Metformin + Lifestyle Intervention
intervention type: Other
intervention name: Placebo
description: Placebo taken by mouth twice daily for 4, 30 day cycles.
arm group label: Placebo
arm group label: Placebo + Lifestyle Intervention
other name: sugar pill
intervention type: Procedure
intervention name: Endometrial Biopsy
description: Endometrial biopsies obtained at baseline and after 4 months.
arm group label: Metformin
arm group label: Metformin + Lifestyle Intervention
arm group label: Placebo
arm group label: Placebo + Lifestyle Intervention
intervention type: Behavioral
intervention name: Lifestyle Intervention
description: Lifestyle intervention consists of 16 in-person sessions offered over a 4 month period.
arm group label: Metformin + Lifestyle Intervention
arm group label: Placebo + Lifestyle Intervention
intervention type: Behavioral
intervention name: Questionnaires
description: Completion of questionnaires about diet and exercise at baseline, during treatment and at end of study. Questionnaires take about 30-40 minutes to complete.
arm group label: Metformin
arm group label: Metformin + Lifestyle Intervention
arm group label: Placebo
arm group label: Placebo + Lifestyle Intervention
other name: surveys
criteria: 
gender: Female
minimum age: 50 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Karen H. Lu, MD
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
facility: 
country: United States
url: http://www.mdanderson.org
description: University of Texas MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Endometrial Neoplasms
mesh term: Metformin