<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/NCT04493788</url>
  </required_header>
  <id_info>
    <org_study_id>MOLPA-2020253</org_study_id>
    <nct_id>NCT04493788</nct_id>
  </id_info>
  <brief_title>Molecular Basis of PCOS in Oocytes and Surrounding Cells</brief_title>
  <official_title>Novel Molecular Characterization of Oocytes and Cumulus Cells From Women With Polycystic Ovarian Syndrome (PCOS) Phenotype A</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitair Ziekenhuis Brussel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitair Ziekenhuis Brussel</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age that is&#xD;
      characterized by elevated androgen levels, ovulatory dysfunction and polycystic ovarian&#xD;
      morphology (PCOM). Moreover, has been associated to insulin resistance, obesity, type 2&#xD;
      diabetes and infertility.&#xD;
&#xD;
      Women with PCOS are a heterogeneous group, and specific PCOS phenotype could have a&#xD;
      substantial impact on oocyte quality and molecular profile. Regarding the Rotterdam criteria&#xD;
      for PCOS, four different phenotypes of the syndrome are defined (A, B, C, D). Phenotypic&#xD;
      group A is the most frequent and severe subtype of PCOS. It is described that patients with&#xD;
      so-called phenotype A exhibit a significantly increased risk of pregnancy complications&#xD;
      compared to women with more favorable PCOS phenotypes. Specifically, this clinical-laboratory&#xD;
      study will focus on the molecular characterization of PCOS phenotype A.&#xD;
&#xD;
      Epigenetic are external modifications to DNA that affect how cells &quot;read&quot; genes. These&#xD;
      external modifications have garnered attention in the pathogenesis of PCOS since epigenetics&#xD;
      changes have been reported in various organs in women with the condition. However, remains&#xD;
      unknown whether these alterations are also found in the egg and in its surrounding cells.&#xD;
&#xD;
      Further research is needed to understand the PCOS disorder and to design treatments that can&#xD;
      ameliorate the symptoms of the disease. In particular, this project aims to generate the&#xD;
      molecular profiles of PCOS phenotype A eggs and surrounding cells and compare them with the&#xD;
      ones obtained from and healthy controls. This approach involves the aspiration of immature&#xD;
      eggs without hormonal stimulation or with stimulation of only a few days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 2020</start_date>
  <completion_date type="Anticipated">July 2022</completion_date>
  <primary_completion_date type="Anticipated">July 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>24 Months</target_duration>
  <primary_outcome>
    <measure>DNA methylation profiles in oocytes and cumulus cells</measure>
    <time_frame>This information is expected to be generated in 24 months</time_frame>
    <description>On of the primary outcome measure of this project will be the generation of DNA methylation profile of PCOS oocytes and paired cumulus cells using single-cell and low-cell parallel sequencing, respectively.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gene expression profiles in oocytes and cumulus cells</measure>
    <time_frame>This information is expected to be generated in 24 months</time_frame>
    <description>Another primary outcome measure of this project will be the generation of gene expression profile of PCOS oocytes and paired cumulus cells using single-cell and low-cell parallel sequencing, respectively.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <arm_group>
    <arm_group_label>PCOS group</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood test, ultrasound and egg retrieval</intervention_name>
    <description>Blood tests will be performed to determine free testosterone levels, anti-mullerian hormone (AMH) and lipid profile including fasting plasma glucose and insulin. Women from both PCOS and control groups will be minimally stimulated with gonadotrophins and cumulus-oocytes complexes (COCs) will be aspirated from small antral follicles (2-8mm) without any ovulation triggering. Specifically, administration of highly purified human menopausal gonadotropin (HP-hMG) will start on cycle Day 3 of the menstrual period or a withdrawal bleeding. A pelvic ultrasound scan will be performed in the morning of the last stimulation day to schedule the oocyte collection. Cumulus-oocyte complexes retrieved 42 hours after the last gonadotropin injection will be collected, washed, denuded and individually stored for further molecular characterization.</description>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_label>PCOS group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Research material will be collected from (i) PCOS patients with phenotype A undergoing IVM&#xD;
        who donate part of their oocytes for research, and (ii) women with normal ovaries and&#xD;
        androgen levels who also donate the total amount of the retrieved oocytes for research.&#xD;
        Participants between the ages of 18 and 37 will be enrolled through correspondent&#xD;
        recruitment programs running in the Centre for Reproductive Medicine of UZ Brussel (CRG).&#xD;
        BMI will be determined and blood tests will be performed to determine free testosterone&#xD;
        levels, AMH and lipid profile including fasting plasma glucose and insulin. The PCOS group&#xD;
        will include patients with phenotype A and the age-matched control groups will include&#xD;
        volunteers with normal androgen levels.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  women between the ages of 18 and 37&#xD;
&#xD;
          -  biochemical hyperandrogenism&#xD;
&#xD;
          -  ovulatory dysfunction&#xD;
&#xD;
          -  polycystic ovaries)&#xD;
&#xD;
          -  BMI &gt; 25.&#xD;
&#xD;
          -  normal andro-gen levels&#xD;
&#xD;
          -  normal ovarian function&#xD;
&#xD;
          -  normal ovarian morphology&#xD;
&#xD;
          -  BMI &lt; 29.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  congenital adrenal hyperplasia&#xD;
&#xD;
          -  Cushing's syndrome&#xD;
&#xD;
          -  androgenic-secreting tumor&#xD;
&#xD;
          -  high (&gt;grade 2) grade endometriosis&#xD;
&#xD;
          -  major uterine or ovarian abnormalities&#xD;
&#xD;
          -  pregnant women&#xD;
&#xD;
          -  volunteers with metabolic syndrome&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>37 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>July 30, 2020</last_update_submitted>
  <last_update_submitted_qc>July 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2020</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>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Syndrome</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/NCT04493788
org study id: MOLPA-2020253
nct id: NCT04493788
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age that is
      characterized by elevated androgen levels, ovulatory dysfunction and polycystic ovarian
      morphology (PCOM). Moreover, has been associated to insulin resistance, obesity, type 2
      diabetes and infertility.

      Women with PCOS are a heterogeneous group, and specific PCOS phenotype could have a
      substantial impact on oocyte quality and molecular profile. Regarding the Rotterdam criteria
      for PCOS, four different phenotypes of the syndrome are defined (A, B, C, D). Phenotypic
      group A is the most frequent and severe subtype of PCOS. It is described that patients with
      so-called phenotype A exhibit a significantly increased risk of pregnancy complications
      compared to women with more favorable PCOS phenotypes. Specifically, this clinical-laboratory
      study will focus on the molecular characterization of PCOS phenotype A.

      Epigenetic are external modifications to DNA that affect how cells "read" genes. These
      external modifications have garnered attention in the pathogenesis of PCOS since epigenetics
      changes have been reported in various organs in women with the condition. However, remains
      unknown whether these alterations are also found in the egg and in its surrounding cells.

      Further research is needed to understand the PCOS disorder and to design treatments that can
      ameliorate the symptoms of the disease. In particular, this project aims to generate the
      molecular profiles of PCOS phenotype A eggs and surrounding cells and compare them with the
      ones obtained from and healthy controls. This approach involves the aspiration of immature
      eggs without hormonal stimulation or with stimulation of only a few days.
observational model: Case-Control
time perspective: Prospective
measure: DNA methylation profiles in oocytes and cumulus cells
time frame: This information is expected to be generated in 24 months
description: On of the primary outcome measure of this project will be the generation of DNA methylation profile of PCOS oocytes and paired cumulus cells using single-cell and low-cell parallel sequencing, respectively.
measure: Gene expression profiles in oocytes and cumulus cells
time frame: This information is expected to be generated in 24 months
description: Another primary outcome measure of this project will be the generation of gene expression profile of PCOS oocytes and paired cumulus cells using single-cell and low-cell parallel sequencing, respectively.
arm group label: PCOS group
arm group label: Control group
intervention type: Other
intervention name: Blood test, ultrasound and egg retrieval
description: Blood tests will be performed to determine free testosterone levels, anti-mullerian hormone (AMH) and lipid profile including fasting plasma glucose and insulin. Women from both PCOS and control groups will be minimally stimulated with gonadotrophins and cumulus-oocytes complexes (COCs) will be aspirated from small antral follicles (2-8mm) without any ovulation triggering. Specifically, administration of highly purified human menopausal gonadotropin (HP-hMG) will start on cycle Day 3 of the menstrual period or a withdrawal bleeding. A pelvic ultrasound scan will be performed in the morning of the last stimulation day to schedule the oocyte collection. Cumulus-oocyte complexes retrieved 42 hours after the last gonadotropin injection will be collected, washed, denuded and individually stored for further molecular characterization.
arm group label: Control group
arm group label: PCOS group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 37 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Syndrome