<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/NCT03043924</url>
  </required_header>
  <id_info>
    <org_study_id>2016_22</org_study_id>
    <secondary_id>2016-A01391-50</secondary_id>
    <nct_id>NCT03043924</nct_id>
  </id_info>
  <brief_title>Functional Study of the Hypothalamus in Magnetic Resonance Imaging (MRI) in Polycystic Ovary Syndrome (PCOS)</brief_title>
  <acronym>MRI-PCOS</acronym>
  <official_title>Functional Study of the Hypothalamus in High-resolution Magnetic Resonance Imaging (MRI) in Women With Polycystic Ovary Syndrome (PCOS): a Comparative Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Research Agency, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Lille</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 aim to evaluate whether activation of the hypothalamic-pituitary-gonadal axis in PCOS is&#xD;
      associated with transient microstructural and metabolic changes in the female hypothalamus&#xD;
      using MRI approaches to assess water diffusion and measure proton magnetic resonance spectra.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the Apparent Diffusion Coefficient (ADC)</measure>
    <time_frame>Baseline and 3 months after treatment start</time_frame>
    <description>The change in the ADC will be analyzed in healthy volunteers and PCOS women before starting the oral contraceptives, and next during the third sequence of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the metabolite concentrations</measure>
    <time_frame>Baseline and 3 months after treatment start</time_frame>
    <description>The change in the metabolite concentrations will be analyzed in the two groups before starting the oral contraceptives, and next during the third sequence of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation coefficient (Spearman or Pearson) between the ADC and serum hormonal levels (FSH,luteinizing hormone,oestradiol, AMH)</measure>
    <time_frame>Baseline and 3 months after treatment start</time_frame>
    <description>The correlation between ADC and hormonal levels in the two groups will be analysed before starting the contraceptive treatment and during the third processing sequence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation coefficient (Spearman or Pearson) between the metabolite concentrations and serum hormonal levels (FSH, luteinizing hormone, oestradiol, AMH)</measure>
    <time_frame>Baseline and 3 months after treatment start</time_frame>
    <description>The correlation between metabolite concentrations and hormonal levels in the two groups will be analysed before starting the contraceptive treatment and during the third processing sequence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma GnRH concentration before and after treatment (PCOS patient and control group)</measure>
    <time_frame>Baseline and 3 months after treatment start</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between brain metabolite concentrations and plasma GnRH concentration before and after contraception.</measure>
    <time_frame>Baseline and 3 months after treatment start</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">52</enrollment>
  <condition>Polycystic Ovary Syndrome</condition>
  <arm_group>
    <arm_group_label>PCOS women</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>26 PCOS women who receive consultation for hyperandrogenism needing treatment with Cyproterone Acetate + estradiol will be recruited.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>26 Healthy volunteers subjects who receive consultation contemplating oral contraceptives (Levonorgestrel, Ethinyl Estradiol 0.1-0.02Mg Oral Tablet ) will be recruited.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyproterone Acetate + estradiol</intervention_name>
    <description>PCOS will receive:&#xD;
50mg cyproterone acetate (Androcur®) in combination with p.o. 2mg estradiol daily</description>
    <arm_group_label>PCOS women</arm_group_label>
    <other_name>Androcur, Provames</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levonorgestrel, Ethinyl Estradiol 0.1-0.02Mg Oral Tablet</intervention_name>
    <description>Healthy volunteers receive combined oral contraceptive (COC) consisting 0.02 mg ethinylestradiol and 0.1mg of progestins (Leeloo Gé®)</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <other_name>Leeloo Gé®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For all subjects&#xD;
&#xD;
          -  Aged from 19 to 30 years&#xD;
&#xD;
          -  Body mass index : 18-25&#xD;
&#xD;
          -  Informed consent before inclusion&#xD;
&#xD;
          -  Do not smoke the 3 days before the MRI&#xD;
&#xD;
        For Healthy volunteers subjects :&#xD;
&#xD;
          -  Regular cycles (between 25 and 35 days) AND ovulatory.&#xD;
&#xD;
          -  No signs of hyperandrogenism.&#xD;
&#xD;
          -  Subjects desirous of taking oral contraceptives (estrogen/progestin combination).&#xD;
&#xD;
          -  For the realization of the 2nd MRI: to be during the 3rd month of a treatment well&#xD;
             followed by oestro-progestative monophasic minidose to 0,02mg of Ethinyl-oestradiol /&#xD;
             0,1mg Levonorgestrel.&#xD;
&#xD;
        PCOS women:&#xD;
&#xD;
          -  PCOS defined by Rotterdam criteria&#xD;
&#xD;
          -  Needing a treatment with cyproterone acetate&#xD;
&#xD;
          -  To carry out the 2nd MRI: to be in progress during the 3rd month of a treatment well&#xD;
             followed by 50 mg of Cyproterone acetate in association with 2mg / day of natural&#xD;
             estradiol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hormone treatment within 3 months prior to inclusion (including birth control pill )&#xD;
&#xD;
          -  On-going pregnancy (determined before each MRI scan visit)&#xD;
&#xD;
          -  Claustrophobia&#xD;
&#xD;
          -  Any metal or foreign implants (e.g., aneurysm clips, ear implants, heart pacemakers or&#xD;
             defibrillators)&#xD;
&#xD;
          -  Diabetes or known dysthyroidism.&#xD;
&#xD;
          -  Current substance abuse (including smoking more than 5 cigarettes/day; determined&#xD;
             using drug screening at the screening visit)&#xD;
&#xD;
          -  Pregnancy or breastfeeding the last 3 months.&#xD;
&#xD;
          -  Practice of intense physical exercise (ex jogging&gt; 10km) the day before the MRI.&#xD;
&#xD;
          -  Person incapable of consenting, or enjoying legal protection (guardianship /&#xD;
             curatorship).&#xD;
&#xD;
          -  Unability to understand the treatment protocol&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Didier Dewailly, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Jeanne de Flandres, CHU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <last_update_submitted>November 8, 2022</last_update_submitted>
  <last_update_submitted_qc>November 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hypothalamus</keyword>
  <keyword>Diffusion Magnetic Resonance Imaging</keyword>
  <keyword>Magnetic Resonance Spectroscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyproterone Acetate</mesh_term>
    <mesh_term>Estradiol 17 beta-cypionate</mesh_term>
    <mesh_term>Estradiol 3-benzoate</mesh_term>
    <mesh_term>Levonorgestrel</mesh_term>
    <mesh_term>Ethinyl Estradiol</mesh_term>
    <mesh_term>Estradiol</mesh_term>
    <mesh_term>Polyestradiol phosphate</mesh_term>
    <mesh_term>Cyproterone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03043924
org study id: 2016_22
secondary id: 2016-A01391-50
nct id: NCT03043924
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The aim to evaluate whether activation of the hypothalamic-pituitary-gonadal axis in PCOS is
      associated with transient microstructural and metabolic changes in the female hypothalamus
      using MRI approaches to assess water diffusion and measure proton magnetic resonance spectra.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in the Apparent Diffusion Coefficient (ADC)
time frame: Baseline and 3 months after treatment start
description: The change in the ADC will be analyzed in healthy volunteers and PCOS women before starting the oral contraceptives, and next during the third sequence of treatment.
measure: Change in the metabolite concentrations
time frame: Baseline and 3 months after treatment start
description: The change in the metabolite concentrations will be analyzed in the two groups before starting the oral contraceptives, and next during the third sequence of treatment.
measure: Correlation coefficient (Spearman or Pearson) between the ADC and serum hormonal levels (FSH,luteinizing hormone,oestradiol, AMH)
time frame: Baseline and 3 months after treatment start
description: The correlation between ADC and hormonal levels in the two groups will be analysed before starting the contraceptive treatment and during the third processing sequence.
measure: Correlation coefficient (Spearman or Pearson) between the metabolite concentrations and serum hormonal levels (FSH, luteinizing hormone, oestradiol, AMH)
time frame: Baseline and 3 months after treatment start
description: The correlation between metabolite concentrations and hormonal levels in the two groups will be analysed before starting the contraceptive treatment and during the third processing sequence.
measure: Plasma GnRH concentration before and after treatment (PCOS patient and control group)
time frame: Baseline and 3 months after treatment start
measure: Correlation between brain metabolite concentrations and plasma GnRH concentration before and after contraception.
time frame: Baseline and 3 months after treatment start
arm group label: PCOS women
arm group type: Other
description: 26 PCOS women who receive consultation for hyperandrogenism needing treatment with Cyproterone Acetate + estradiol will be recruited.
arm group label: Healthy volunteers
arm group type: Other
description: 26 Healthy volunteers subjects who receive consultation contemplating oral contraceptives (Levonorgestrel, Ethinyl Estradiol 0.1-0.02Mg Oral Tablet ) will be recruited.
intervention type: Drug
intervention name: Cyproterone Acetate + estradiol
description: PCOS will receive:
50mg cyproterone acetate (Androcur®) in combination with p.o. 2mg estradiol daily
arm group label: PCOS women
other name: Androcur, Provames
intervention type: Drug
intervention name: Levonorgestrel, Ethinyl Estradiol 0.1-0.02Mg Oral Tablet
description: Healthy volunteers receive combined oral contraceptive (COC) consisting 0.02 mg ethinylestradiol and 0.1mg of progestins (Leeloo Gé®)
arm group label: Healthy volunteers
other name: Leeloo Gé®
criteria: 
gender: Female
minimum age: 19 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Didier Dewailly, MD,PhD
role: Principal Investigator
affiliation: University Hospital, Lille
facility: 
country: France
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Syndrome
mesh term: Cyproterone Acetate
mesh term: Estradiol 17 beta-cypionate
mesh term: Estradiol 3-benzoate
mesh term: Levonorgestrel
mesh term: Ethinyl Estradiol
mesh term: Estradiol
mesh term: Polyestradiol phosphate
mesh term: Cyproterone
sharing ipd: No