<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/NCT04424576</url>
  </required_header>
  <id_info>
    <org_study_id>IRB# 0000779</org_study_id>
    <nct_id>NCT04424576</nct_id>
  </id_info>
  <brief_title>Ovarian Morphology in Girls</brief_title>
  <acronym>OMG</acronym>
  <official_title>Trajectory of Ovarian Morphology During the Adolescent Reproductive Transition</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Children's Mercy Hospital Kansas City</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>
      Establishment of regular menstrual cycles is a key component of reproductive maturation and a&#xD;
      recognized vital sign for health and well-being. Irregular menstrual cycles are especially&#xD;
      common for the first 2-3 years after an adolescent's first menstrual period (i.e., menarche),&#xD;
      which delays the identification and diagnosis of early reproductive disturbances such as&#xD;
      polycystic ovary syndrome (PCOS). The purpose of this research study is to determine whether&#xD;
      the ovary can serve as a reliable predictor of normal or abnormal development by following&#xD;
      the trajectory of ovarian morphology in conjunction with menstrual cyclicity using 3D&#xD;
      transabdominal ultrasound imaging in a prospective cohort study of adolescents. A secondary&#xD;
      objective is to identify potential environmental factors such as diet and the gut microbiome&#xD;
      which influence the trajectory towards normal or abnormal reproductive development.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Establishment of regular menstrual cycles is a key component of reproductive maturation and a&#xD;
      recognized vital sign for health and well-being. Irregular menstrual cycles are especially&#xD;
      common for the first 2-3 years after an adolescent's first menstrual period (i.e., menarche),&#xD;
      which delays the identification and diagnosis of early reproductive perturbations and&#xD;
      subsequent future disease risk. Therefore, the objectives of this study are to determine&#xD;
      whether there are distinct aspects of ovarian morphology that predict the likelihood of&#xD;
      regular menses or cycle irregularity at 2y post-menarche and to determine whether diet or&#xD;
      lifestyle (such as quality of sleep) contribute to changes in the ovaries and period&#xD;
      patterns.&#xD;
&#xD;
      A group of up to 60 adolescents will be enrolled into a prospective longitudinal cohort&#xD;
      study. Participants will attend four study visits to their location's respective clinical&#xD;
      research center. Study visits will occur at four distinct time points post-menarche: 6-10&#xD;
      months, 11-13 months, 17-19 months, and 23-25 months.&#xD;
&#xD;
      Prior to each of the study visits, participants will undergo one planned 24-hr dietary recall&#xD;
      by a member of the research team and self-collect a stool sample. Participants will be asked&#xD;
      to fast the night before the study visit. At each study visit, participants will undergo the&#xD;
      following assessments:&#xD;
&#xD;
      A 3D transabdominal ultrasound of the ovaries and uterus.&#xD;
&#xD;
      A fasting blood sample, obtained via venipuncture.&#xD;
&#xD;
      A series of anthropometric assessments, including: height, weight, waist and hip&#xD;
      circumference, blood pressure, heart rate, and body fat percentage obtained using a&#xD;
      bioimpedance scale.&#xD;
&#xD;
      Tanner stage assessment, using a standardized self-report scoring scheme and by a trained&#xD;
      member of the research team who is blinded to the results of the self-reported tanner stage.&#xD;
&#xD;
      Acne scoring, using a standardized scoring scheme by a member of the research team.&#xD;
&#xD;
      Hirsutism assessment, obtained by visually inspecting nine pre-defined regions of the body&#xD;
      for terminal hair growth using a standardized scoring scheme by a trained member of the&#xD;
      research team.&#xD;
&#xD;
      Urine sample, self-collected by the participant after the transabdominal ultrasound.&#xD;
&#xD;
      24-hour dietary recall.&#xD;
&#xD;
      Physical activity questionnaire.&#xD;
&#xD;
      Two sleep questionnaires, including questions about sleep hygiene, sleep quality, and&#xD;
      circadian rhythms.&#xD;
&#xD;
      In between study visits, participants will maintain menstrual cycle diaries and medication&#xD;
      diaries.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 31, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Ovarian size</measure>
    <time_frame>24 months</time_frame>
    <description>Changes in ovarian size over the first 2y post-menarche will be assessed and compared across cohorts.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Follicle counts</measure>
    <time_frame>24 months</time_frame>
    <description>Follicle counts, expressed as follicle number per ovary (FNPO) and follicle number per cross-section (FNPS), will be assessed over the first 2y post-menarche and compared across cohorts. Numbers of large follicles (&gt;10 mm diameter) and small follicles (&lt;10 mm diameter) will also be compared across cohorts.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Menstrual cycle status</measure>
    <time_frame>24 months</time_frame>
    <description>Menstrual cycle status (i.e., regular versus irregular menstrual cycles) will be assessed using menstrual cycle records maintained by participants over the course of the study. Changes in menstrual cycle status over the 2y post-menarche and relationships between menstrual cycle status and other physiological and lifestyle factors will be examined.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body composition</measure>
    <time_frame>24 months</time_frame>
    <description>Changes in percent body fat, obtained using a bioimpedence scale, will be assessed over the first 2y post-menarche and compared across cohorts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leutenizing hormone (LH), follicle stimulating hormone (FSH), estradiol, progesterone, anti-mullerian hormone, free and total testosterone, and androstenedione</measure>
    <time_frame>24 months</time_frame>
    <description>Serum levels of these reproductive hormones will be assessed over the first 2y post-menarche and compared across cohorts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep quality</measure>
    <time_frame>24 months</time_frame>
    <description>Sleep quality will be assessed using two questionnaires: the Morningness-Eveningness Scale for Children and the Children's Report of Sleep Patterns. Sleep quality will be assessed over the first 2y post-menarche and compared across cohorts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dietary composition</measure>
    <time_frame>24 months</time_frame>
    <description>Dietary composition (i.e., macro and micronutrient totals, total energy intake) will be assessed using two 24-Hour Food Frequency Questionnaires administered at each gynecological time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gut microbiome richness and diversity</measure>
    <time_frame>24 months</time_frame>
    <description>Gut microbiome richness and diversity will be assessed over the first 2y post-menarche and compared across cohorts.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Amenorrhea</condition>
  <condition>Oligomenorrhea</condition>
  <condition>Puberty</condition>
  <arm_group>
    <arm_group_label>Regular Menstrual Cycles</arm_group_label>
    <description>22 adolescents with regular menstrual cycles (i.e., once every 4-6 weeks) will be enrolled within 11 months of menarche.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Irregular Menstrual Cycles</arm_group_label>
    <description>26 adolescents with irregular menstrual cycles (i.e., &lt; 4 weeks or &gt; 6 weeks between periods) will be enrolled within 11 months of menarche.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood, Urine, Stool&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Female adolescents between the ages of 9 and 17 years who achieved menarche (i.e., very&#xD;
        first period) within the past 11 months will be recruited.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Female adolescents aged 9 to 17 years&#xD;
&#xD;
          -  Menarche within 11 months of the enrollment visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current or recent use of medications or supplements known or suspected to interfere&#xD;
             with reproductive or metabolic function in the past 2 months (e.g., contraceptives,&#xD;
             metformin, steroids, anti-seizure medications)&#xD;
&#xD;
          -  Untreated and/or unstable medical or mental health condition known or suspected to&#xD;
             interfere with reproductive or metabolic function&#xD;
&#xD;
          -  Currently pregnant or breast feeding&#xD;
&#xD;
          -  History of ovarian surgery&#xD;
&#xD;
          -  Presence of significant acute or chronic illness which may interfere with study&#xD;
             participation&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Eligibility is limited to biologically female individuals because the primary study endpoints include the ovary and menstrual cycle.</gender_description>
    <minimum_age>9 Years</minimum_age>
    <maximum_age>17 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>Tania Burgert, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Mercy Hospital Kansas City</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Romina Barral, MD MSCR FAPP</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Mercy Hospital Kansas City</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Heidi Vanden Brink, PhD</last_name>
    <phone>816-960-4186</phone>
    <email>hvandenbrink@cmh.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Marla E Lujan, PhD</last_name>
    <phone>607-255-3153</phone>
    <email>mel245@cornell.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Children's Mercy Hospital</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64108</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Heidi Vanden Brink, PhD</last_name>
      <phone>816-960-4186</phone>
    </contact>
    <investigator>
      <last_name>Tania Burgert, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Romina Barral, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Cornell University - Human Metabolic Research Unit</name>
      <address>
        <city>Ithaca</city>
        <state>New York</state>
        <zip>14853</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Suspended</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>September 23, 2022</last_update_submitted>
  <last_update_submitted_qc>September 23, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ovary</keyword>
  <keyword>Transabdominal Ultrasound</keyword>
  <keyword>Menarche</keyword>
  <keyword>Periods</keyword>
  <keyword>Microbiome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amenorrhea</mesh_term>
    <mesh_term>Oligomenorrhea</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/NCT04424576
org study id: IRB# 0000779
nct id: NCT04424576
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Establishment of regular menstrual cycles is a key component of reproductive maturation and a
      recognized vital sign for health and well-being. Irregular menstrual cycles are especially
      common for the first 2-3 years after an adolescent's first menstrual period (i.e., menarche),
      which delays the identification and diagnosis of early reproductive disturbances such as
      polycystic ovary syndrome (PCOS). The purpose of this research study is to determine whether
      the ovary can serve as a reliable predictor of normal or abnormal development by following
      the trajectory of ovarian morphology in conjunction with menstrual cyclicity using 3D
      transabdominal ultrasound imaging in a prospective cohort study of adolescents. A secondary
      objective is to identify potential environmental factors such as diet and the gut microbiome
      which influence the trajectory towards normal or abnormal reproductive development.
Establishment of regular menstrual cycles is a key component of reproductive maturation and a
      recognized vital sign for health and well-being. Irregular menstrual cycles are especially
      common for the first 2-3 years after an adolescent's first menstrual period (i.e., menarche),
      which delays the identification and diagnosis of early reproductive perturbations and
      subsequent future disease risk. Therefore, the objectives of this study are to determine
      whether there are distinct aspects of ovarian morphology that predict the likelihood of
      regular menses or cycle irregularity at 2y post-menarche and to determine whether diet or
      lifestyle (such as quality of sleep) contribute to changes in the ovaries and period
      patterns.

      A group of up to 60 adolescents will be enrolled into a prospective longitudinal cohort
      study. Participants will attend four study visits to their location's respective clinical
      research center. Study visits will occur at four distinct time points post-menarche: 6-10
      months, 11-13 months, 17-19 months, and 23-25 months.

      Prior to each of the study visits, participants will undergo one planned 24-hr dietary recall
      by a member of the research team and self-collect a stool sample. Participants will be asked
      to fast the night before the study visit. At each study visit, participants will undergo the
      following assessments:

      A 3D transabdominal ultrasound of the ovaries and uterus.

      A fasting blood sample, obtained via venipuncture.

      A series of anthropometric assessments, including: height, weight, waist and hip
      circumference, blood pressure, heart rate, and body fat percentage obtained using a
      bioimpedance scale.

      Tanner stage assessment, using a standardized self-report scoring scheme and by a trained
      member of the research team who is blinded to the results of the self-reported tanner stage.

      Acne scoring, using a standardized scoring scheme by a member of the research team.

      Hirsutism assessment, obtained by visually inspecting nine pre-defined regions of the body
      for terminal hair growth using a standardized scoring scheme by a trained member of the
      research team.

      Urine sample, self-collected by the participant after the transabdominal ultrasound.

      24-hour dietary recall.

      Physical activity questionnaire.

      Two sleep questionnaires, including questions about sleep hygiene, sleep quality, and
      circadian rhythms.

      In between study visits, participants will maintain menstrual cycle diaries and medication
      diaries.
observational model: Cohort
time perspective: Prospective
measure: Ovarian size
time frame: 24 months
description: Changes in ovarian size over the first 2y post-menarche will be assessed and compared across cohorts.
measure: Follicle counts
time frame: 24 months
description: Follicle counts, expressed as follicle number per ovary (FNPO) and follicle number per cross-section (FNPS), will be assessed over the first 2y post-menarche and compared across cohorts. Numbers of large follicles (>10 mm diameter) and small follicles (<10 mm diameter) will also be compared across cohorts.
measure: Menstrual cycle status
time frame: 24 months
description: Menstrual cycle status (i.e., regular versus irregular menstrual cycles) will be assessed using menstrual cycle records maintained by participants over the course of the study. Changes in menstrual cycle status over the 2y post-menarche and relationships between menstrual cycle status and other physiological and lifestyle factors will be examined.
measure: Body composition
time frame: 24 months
description: Changes in percent body fat, obtained using a bioimpedence scale, will be assessed over the first 2y post-menarche and compared across cohorts.
measure: Leutenizing hormone (LH), follicle stimulating hormone (FSH), estradiol, progesterone, anti-mullerian hormone, free and total testosterone, and androstenedione
time frame: 24 months
description: Serum levels of these reproductive hormones will be assessed over the first 2y post-menarche and compared across cohorts.
measure: Sleep quality
time frame: 24 months
description: Sleep quality will be assessed using two questionnaires: the Morningness-Eveningness Scale for Children and the Children's Report of Sleep Patterns. Sleep quality will be assessed over the first 2y post-menarche and compared across cohorts.
measure: Dietary composition
time frame: 24 months
description: Dietary composition (i.e., macro and micronutrient totals, total energy intake) will be assessed using two 24-Hour Food Frequency Questionnaires administered at each gynecological time point.
measure: Gut microbiome richness and diversity
time frame: 24 months
description: Gut microbiome richness and diversity will be assessed over the first 2y post-menarche and compared across cohorts.
arm group label: Regular Menstrual Cycles
description: 22 adolescents with regular menstrual cycles (i.e., once every 4-6 weeks) will be enrolled within 11 months of menarche.
arm group label: Irregular Menstrual Cycles
description: 26 adolescents with irregular menstrual cycles (i.e., < 4 weeks or > 6 weeks between periods) will be enrolled within 11 months of menarche.
Blood, Urine, Stool
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Eligibility is limited to biologically female individuals because the primary study endpoints include the ovary and menstrual cycle.
minimum age: 9 Years
maximum age: 17 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marla E Lujan, PhD
role: Principal Investigator
affiliation: Cornell University
last name: Tania Burgert, MD
role: Principal Investigator
affiliation: Children's Mercy Hospital Kansas City
last name: Romina Barral, MD MSCR FAPP
role: Principal Investigator
affiliation: Children's Mercy Hospital Kansas City
last name: Heidi Vanden Brink, PhD
phone: 816-960-4186
email: hvandenbrink@cmh.edu
last name: Marla E Lujan, PhD
phone: 607-255-3153
email: mel245@cornell.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
facility: 
status: Suspended
country: United States
responsible party type: Sponsor
mesh term: Amenorrhea
mesh term: Oligomenorrhea