<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/NCT03306849</url>
  </required_header>
  <id_info>
    <org_study_id>1410015577</org_study_id>
    <nct_id>NCT03306849</nct_id>
  </id_info>
  <brief_title>Ultrasonographic Evaluation of Anovulatory Disorders in Lean and Overweight Women</brief_title>
  <official_title>Ultrasonographic Evaluation of Anovulatory Disorders in Lean and Overweight Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Cornell University</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 would like to determine whether ultrasound features of the ovaries can be&#xD;
      used to reliably diagnose different types of anovulatory disorders in women across all body&#xD;
      types. The study will also try to establish whether ultrasound features of the ovary can&#xD;
      reflect the degree of reproductive and metabolic problems that a woman with irregular or&#xD;
      absent periods might be experiencing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is being conducted in order to determine if ultrasound features of the ovaries can&#xD;
      be used to reliably diagnose different types of anovulatory disorders in women across all&#xD;
      body types. The study will also try to establish whether ultrasound features of the ovary can&#xD;
      reflect the degree of reproductive and metabolic problems that a woman with irregular or&#xD;
      absent periods might be experiencing. In this way, the researchers can help to maximize the&#xD;
      information that can be received when using ultrasound to evaluate patients with concerns&#xD;
      over irregular menstrual cycles and/or infertility.&#xD;
&#xD;
      The ovaries are the site of egg production and normally release one egg every month. The&#xD;
      process of releasing an egg is called ovulation. The act of releasing an egg is the body's&#xD;
      way of ensuring a woman's fertility each month during her reproductive years. There are a&#xD;
      number of reasons why ovulation may not occur regularly in women. Some of these reasons are&#xD;
      believed to relate to male hormone production (i.e. androgens), body composition, nutrition&#xD;
      and overall metabolic health. However, the precise ways in which these factors affect&#xD;
      ovulation are unknown.&#xD;
&#xD;
      The researchers plan to evaluate how the ovaries look and function in a large group of women.&#xD;
      Their goal is to recruit both lean and overweight women to this study and include both women&#xD;
      that have regular, predictable menstrual cycles as well as those that have infrequent or&#xD;
      absent menstrual cycles. The researchers will include women with irregular cycles due to&#xD;
      increased androgen production, or hyperandrogenic anovulation - as well as those that have&#xD;
      irregular cycles but normal androgen levels or normoandrogenic anovulation. The researchers&#xD;
      will use ultrasound to collect information on how the ovaries look and function, and then&#xD;
      relate the features of the ovaries to body composition, reproductive and metabolic hormones&#xD;
      as well as nutritional factors. Because features of the ovaries are expected to be different&#xD;
      in lean and overweight women, the researchers hope to develop ultrasound criteria that will&#xD;
      help healthcare providers to diagnosis specific ovulation problems in women across all body&#xD;
      sizes. Together, this research will help to better understand the complex relationship&#xD;
      between nutrition, metabolism and reproductive health in women.&#xD;
&#xD;
      To accomplish these objectives, the investigators plan to recruit 50 women with regular&#xD;
      menstrual cycles, 50 women with normoandrogenic anovulation, and 50 women with&#xD;
      hyperandrogenic anovulation. Their goal is to recruit an equal number of women in each group&#xD;
      who are lean (BMI; Normal weight = 18.5 - 24.9 kg/m2) and overweight or obese (BMI;&#xD;
      Overweight = 25 - 29.9 kg/m2; Obese &gt;= 30kg/m2). Ultrasound scans of the ovaries will be&#xD;
      assessed for the total number, size, and distribution of follicles using both two- and&#xD;
      three-dimensional imaging techniques. Participants will have blood samples collected&#xD;
      determine serum concentrations of luteinizing hormone (LH), follicle stimulating hormone&#xD;
      (FSH), estradiol, progesterone. The following metabolic parameters will be assessed: (1)&#xD;
      75-gram oral glucose tolerance test to characterize glucose and insulin dynamics at 0, 30,&#xD;
      60, 90, and 120 minutes post-glucose ingestion; (2) dual X-ray absorptiometry (DXA) scan to&#xD;
      quantify body fat and lean muscle distribution; (3) vitals and anthropometry assessment to&#xD;
      measure waist and hip circumference, height, weight, blood pressure, and heart rate, and (4)&#xD;
      fasting blood tests to detect serum concentrations of androgens (i.e., total testosterone,&#xD;
      androstenedione, free androgen index) and serum markers of metabolic syndrome (i.e., lipids&#xD;
      and hemoglobin A1C). Participants will complete a food frequency questionnaire and physical&#xD;
      activity questionnaire. A researcher may also provide participants with an accelerometer to&#xD;
      wear for a week.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 2015</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Follicle number per ovary</measure>
    <time_frame>1 day</time_frame>
    <description>The number and size of all follicles in each ovary will be assessed by ultrasonography</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Follicle number per cross section</measure>
    <time_frame>1 day</time_frame>
    <description>The number all follicles in a single cross sectional plane of each ovary will be assessed by ultrasonography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ovarian volume</measure>
    <time_frame>1 day</time_frame>
    <description>The size of each ovary will be determined by ultrasonography for each participant and compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stromal echogenicity on ultrasound</measure>
    <time_frame>1 day</time_frame>
    <description>The brightness of the ovarian stroma in a single cross section will be determined by ultrasonography for each participant and compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ovarian area-stromal area ratio</measure>
    <time_frame>1 day</time_frame>
    <description>The ratio of the stromal area to the total ovarian area of the ovary in a single cross section will be determined by ultrasonography for each participant and compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LH-FSH ratio</measure>
    <time_frame>1 day</time_frame>
    <description>The ratio of circulating LH to FSH concentrations in the serum will be determined for each participant and compared across groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hirsutism Score</measure>
    <time_frame>1 day</time_frame>
    <description>Degree of hirsutism as judged by the Ferriman-Gallwey scale will be determined and compared across groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Androgen concentrations</measure>
    <time_frame>1 day</time_frame>
    <description>Total testosterone, androstenedione and free androgen index concentrations in serum will be determined and compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Menstrual Cycle Length</measure>
    <time_frame>1 day</time_frame>
    <description>Average menstrual cycle length as determined by self-reported history will be determined and compared across groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum markers of metabolic syndrome</measure>
    <time_frame>1 day</time_frame>
    <description>Lipids, glucose and HbA1C concentrations will be determined and compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Pressure</measure>
    <time_frame>1 day</time_frame>
    <description>Blood pressure will be determined and compared across groups. [Time Frame: 1 day]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body mass index</measure>
    <time_frame>1 day</time_frame>
    <description>The ratio of weight to height will be determined and compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist-to-hip ratio</measure>
    <time_frame>1 day</time_frame>
    <description>The ratio of waist circumference to hip circumference will be determined and compared across groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body fat distribution</measure>
    <time_frame>1 day</time_frame>
    <description>Percentage and distribution of fat and lean mass as assessed using DXA technology will be compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>1 day</time_frame>
    <description>Insulin sensitivity will be determined by administration of an oral glucose tolerance test and compared across groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in diet composition assessed via food frequency questionnaire</measure>
    <time_frame>1 day</time_frame>
    <description>A food frequency questionnaire will be administered to assess diet composition for the last three months and will be compared across groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in energy expenditure assessed via a waist-worn accelerometer</measure>
    <time_frame>1 week</time_frame>
    <description>Participants will be asked to wear a small accelerometer device to assess physical activity</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Menstrual Cycle Abnormal</condition>
  <condition>PCOS</condition>
  <condition>Overweight</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>Regular menstrual cycles</arm_group_label>
    <description>Women will be assigned to this category if they report a history of regular menstrual cycles (every 21 to 35 days). Recruitment will be targeted such that equal numbers of lean (BMI &lt;25kg/m2) and overweight or obese (BMI &gt;24.9kg/m2) participate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normoandrogenic anovulation</arm_group_label>
    <description>Women will be assigned to this category if they do not have clinical or biochemical androgen excess and report a history of irregular menstrual cycles (&lt;21 days or &gt;35 days), including women with a pre-existing diagnosis of PCOS. Recruitment will be targeted such that equal numbers of lean (BMI &lt;25kg/m2) and overweight or obese (BMI &gt;24.9kg/m2) participate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hyperandrogenic anovulation</arm_group_label>
    <description>Women will be assigned to this category if they have clinical or biochemical androgen excess and report a history of irregular menstrual cycles (&lt;21 days or &gt;35 days), including women with a pre-existing diagnosis of PCOS. Recruitment will be targeted such that equal numbers of lean (BMI &lt;25kg/m2) and overweight or obese (BMI &gt;24.9kg/m2) participate.</description>
  </arm_group>
  <biospec_retention>None Retained</biospec_retention>
  <biospec_descr>
    <textblock>
      26mL Blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Women must be able to transport to Weill Cornell University. Eligible participants are&#xD;
        between 18-45 years with a BMI of 18.5 kg/m2 or higher. Women are screened and enrolled&#xD;
        following consent based on their response to our advertisements. Women are recruited from&#xD;
        the general population. Enrollment is restricted to the geographical area.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 18-45 years&#xD;
&#xD;
          -  At least 2y post-menarche&#xD;
&#xD;
          -  BMI &gt;18.5kg/m2&#xD;
&#xD;
          -  Good visibility of the ovaries on ultrasound&#xD;
&#xD;
        Either:&#xD;
&#xD;
          -  Regular menstrual cycles (21-35 days);&#xD;
&#xD;
          -  Irregular menstrual cycles (&gt;35 days); or&#xD;
&#xD;
          -  Previous diagnosis of PCOS from a primary care provider&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Weight &gt;300lbs&#xD;
&#xD;
          -  Currently pregnant or breast feeding&#xD;
&#xD;
          -  History of ovarian surgery&#xD;
&#xD;
          -  Use of medications or supplements known or suspected to interfere with reproductive&#xD;
             function and/or glucose and lipid metabolism in the past 3 months&#xD;
&#xD;
          -  Evidence of reproductive aging as assessed by the principal criteria of STRAW+10&#xD;
             stages&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marla E Lujan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cornell University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steven Spandorfer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jeff Pea, BS</last_name>
    <email>jtp239@cornell.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Clinical and Translational Science Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Haneen Aljayyousi, BA</last_name>
      <phone>646-962-8311</phone>
      <email>haa4002@med.cornell.edu</email>
    </contact>
    <investigator>
      <last_name>Steven Spandorfer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>October 6, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>February 9, 2023</last_update_submitted>
  <last_update_submitted_qc>February 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Overweight</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/NCT03306849
org study id: 1410015577
nct id: NCT03306849
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators would like to determine whether ultrasound features of the ovaries can be
      used to reliably diagnose different types of anovulatory disorders in women across all body
      types. The study will also try to establish whether ultrasound features of the ovary can
      reflect the degree of reproductive and metabolic problems that a woman with irregular or
      absent periods might be experiencing.
This study is being conducted in order to determine if ultrasound features of the ovaries can
      be used to reliably diagnose different types of anovulatory disorders in women across all
      body types. The study will also try to establish whether ultrasound features of the ovary can
      reflect the degree of reproductive and metabolic problems that a woman with irregular or
      absent periods might be experiencing. In this way, the researchers can help to maximize the
      information that can be received when using ultrasound to evaluate patients with concerns
      over irregular menstrual cycles and/or infertility.

      The ovaries are the site of egg production and normally release one egg every month. The
      process of releasing an egg is called ovulation. The act of releasing an egg is the body's
      way of ensuring a woman's fertility each month during her reproductive years. There are a
      number of reasons why ovulation may not occur regularly in women. Some of these reasons are
      believed to relate to male hormone production (i.e. androgens), body composition, nutrition
      and overall metabolic health. However, the precise ways in which these factors affect
      ovulation are unknown.

      The researchers plan to evaluate how the ovaries look and function in a large group of women.
      Their goal is to recruit both lean and overweight women to this study and include both women
      that have regular, predictable menstrual cycles as well as those that have infrequent or
      absent menstrual cycles. The researchers will include women with irregular cycles due to
      increased androgen production, or hyperandrogenic anovulation - as well as those that have
      irregular cycles but normal androgen levels or normoandrogenic anovulation. The researchers
      will use ultrasound to collect information on how the ovaries look and function, and then
      relate the features of the ovaries to body composition, reproductive and metabolic hormones
      as well as nutritional factors. Because features of the ovaries are expected to be different
      in lean and overweight women, the researchers hope to develop ultrasound criteria that will
      help healthcare providers to diagnosis specific ovulation problems in women across all body
      sizes. Together, this research will help to better understand the complex relationship
      between nutrition, metabolism and reproductive health in women.

      To accomplish these objectives, the investigators plan to recruit 50 women with regular
      menstrual cycles, 50 women with normoandrogenic anovulation, and 50 women with
      hyperandrogenic anovulation. Their goal is to recruit an equal number of women in each group
      who are lean (BMI; Normal weight = 18.5 - 24.9 kg/m2) and overweight or obese (BMI;
      Overweight = 25 - 29.9 kg/m2; Obese >= 30kg/m2). Ultrasound scans of the ovaries will be
      assessed for the total number, size, and distribution of follicles using both two- and
      three-dimensional imaging techniques. Participants will have blood samples collected
      determine serum concentrations of luteinizing hormone (LH), follicle stimulating hormone
      (FSH), estradiol, progesterone. The following metabolic parameters will be assessed: (1)
      75-gram oral glucose tolerance test to characterize glucose and insulin dynamics at 0, 30,
      60, 90, and 120 minutes post-glucose ingestion; (2) dual X-ray absorptiometry (DXA) scan to
      quantify body fat and lean muscle distribution; (3) vitals and anthropometry assessment to
      measure waist and hip circumference, height, weight, blood pressure, and heart rate, and (4)
      fasting blood tests to detect serum concentrations of androgens (i.e., total testosterone,
      androstenedione, free androgen index) and serum markers of metabolic syndrome (i.e., lipids
      and hemoglobin A1C). Participants will complete a food frequency questionnaire and physical
      activity questionnaire. A researcher may also provide participants with an accelerometer to
      wear for a week.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Follicle number per ovary
time frame: 1 day
description: The number and size of all follicles in each ovary will be assessed by ultrasonography
measure: Follicle number per cross section
time frame: 1 day
description: The number all follicles in a single cross sectional plane of each ovary will be assessed by ultrasonography
measure: Ovarian volume
time frame: 1 day
description: The size of each ovary will be determined by ultrasonography for each participant and compared across groups.
measure: Stromal echogenicity on ultrasound
time frame: 1 day
description: The brightness of the ovarian stroma in a single cross section will be determined by ultrasonography for each participant and compared across groups.
measure: Ovarian area-stromal area ratio
time frame: 1 day
description: The ratio of the stromal area to the total ovarian area of the ovary in a single cross section will be determined by ultrasonography for each participant and compared across groups.
measure: LH-FSH ratio
time frame: 1 day
description: The ratio of circulating LH to FSH concentrations in the serum will be determined for each participant and compared across groups
measure: Hirsutism Score
time frame: 1 day
description: Degree of hirsutism as judged by the Ferriman-Gallwey scale will be determined and compared across groups
measure: Androgen concentrations
time frame: 1 day
description: Total testosterone, androstenedione and free androgen index concentrations in serum will be determined and compared across groups.
measure: Menstrual Cycle Length
time frame: 1 day
description: Average menstrual cycle length as determined by self-reported history will be determined and compared across groups
measure: Serum markers of metabolic syndrome
time frame: 1 day
description: Lipids, glucose and HbA1C concentrations will be determined and compared across groups.
measure: Blood Pressure
time frame: 1 day
description: Blood pressure will be determined and compared across groups. [Time Frame: 1 day]
measure: Body mass index
time frame: 1 day
description: The ratio of weight to height will be determined and compared across groups.
measure: Waist-to-hip ratio
time frame: 1 day
description: The ratio of waist circumference to hip circumference will be determined and compared across groups
measure: Body fat distribution
time frame: 1 day
description: Percentage and distribution of fat and lean mass as assessed using DXA technology will be compared across groups.
measure: Insulin sensitivity
time frame: 1 day
description: Insulin sensitivity will be determined by administration of an oral glucose tolerance test and compared across groups.
measure: Differences in diet composition assessed via food frequency questionnaire
time frame: 1 day
description: A food frequency questionnaire will be administered to assess diet composition for the last three months and will be compared across groups
measure: Differences in energy expenditure assessed via a waist-worn accelerometer
time frame: 1 week
description: Participants will be asked to wear a small accelerometer device to assess physical activity
arm group label: Regular menstrual cycles
description: Women will be assigned to this category if they report a history of regular menstrual cycles (every 21 to 35 days). Recruitment will be targeted such that equal numbers of lean (BMI <25kg/m2) and overweight or obese (BMI >24.9kg/m2) participate.
arm group label: Normoandrogenic anovulation
description: Women will be assigned to this category if they do not have clinical or biochemical androgen excess and report a history of irregular menstrual cycles (<21 days or >35 days), including women with a pre-existing diagnosis of PCOS. Recruitment will be targeted such that equal numbers of lean (BMI <25kg/m2) and overweight or obese (BMI >24.9kg/m2) participate.
arm group label: Hyperandrogenic anovulation
description: Women will be assigned to this category if they have clinical or biochemical androgen excess and report a history of irregular menstrual cycles (<21 days or >35 days), including women with a pre-existing diagnosis of PCOS. Recruitment will be targeted such that equal numbers of lean (BMI <25kg/m2) and overweight or obese (BMI >24.9kg/m2) participate.
26mL Blood
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marla E Lujan, PhD
role: Principal Investigator
affiliation: Cornell University
last name: Steven Spandorfer, MD
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
last name: Jeff Pea, BS
email: jtp239@cornell.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Overweight