<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/NCT03756480</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00188129</org_study_id>
    <secondary_id>R01HD096147</secondary_id>
    <nct_id>NCT03756480</nct_id>
  </id_info>
  <brief_title>Cancer Driving Mutations in Endometriosis Lesions and Development of Progesterone Resistance</brief_title>
  <official_title>Prospective Clinical Study of the Relationship Between Cancer Driving Mutations Found in Endometriotic Implants and the Development of Progesterone Resistance</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins 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>
      This study will test the hypothesis that the molecular changes present in ectopic&#xD;
      endometriosis lesions correlate with progesterone-resistant disease (using the criteria&#xD;
      defined in this study) and are present in matched eutopic endometrium.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Tissues from 100 patients with endometriosis will be analyzed with droplet digital PCR&#xD;
      (ddPCR) targeted sequencing and responders (n=50) will be compared to non-responders (n=50)&#xD;
      after controlling confounding factors.&#xD;
&#xD;
      From a subset of the 100 cases, whole exome sequencing (WES) and Methylation-Specific PCR&#xD;
      (MSP)-based methylation profiling on microdissected epithelium and stroma will be performed&#xD;
      in matched eutopic and ectopic tissues from 20 patients with known cancer-associated&#xD;
      mutations or 20 controls.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 1, 2020</start_date>
  <completion_date type="Anticipated">October 1, 2026</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2026</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Number of somatic cancer driver mutations in progesterone-resistant versus progesterone-sensitive endometriosis lesions.</measure>
    <time_frame>Six month</time_frame>
    <description>Digital droplet PCR will be used to identify somatic cancer-driver mutations with the presence of at least one of KRAS or ARID1A or PIK3CA or PPP2R1A cancer-driver mutations to assess any difference between progesterone-resistant endometriosis and progesterone-sensitive endometriosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of cancer driver mutations in eutopic versus ectopic endometrial tissue in control versus diseased subjects</measure>
    <time_frame>Six month</time_frame>
    <description>Whole exome sequencing in a subset of patients with progesterone-resistant disease and controls will be done using TruSeq Amplicon Cancer Panel (Illumina) to assess the number of cancer driver mutations.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in DNA methylation PCR profile of endometriotic lesions in ectopic versus eutopic endometrium in control versus diseased subjects.</measure>
    <time_frame>One month</time_frame>
    <description>DNA methylation profile of eutopic and ectopic endometrial tissue for cases and controls will be done using Raw Illumina 450K methylation array to assess for any difference.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">135</enrollment>
  <condition>Endometriosis</condition>
  <condition>Endometrial Diseases</condition>
  <arm_group>
    <arm_group_label>Case Group</arm_group_label>
    <description>Clinical or surgical diagnosis of Endometriosis, patients undergoing surgical management&#xD;
100 participants</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <description>No diagnosis of Endometriosis, Patients undergoing Laparoscopic Tubal Ligation&#xD;
35 participants</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Endometrial tissue from ectopic and eutopic sites and blood sample.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Women between the ages of 18-45 undergoing surgical management for endometriosis as cases&#xD;
        and women between ages of 18-45 years undergoing elective tubal ligation and no diagnosis&#xD;
        of endometriosis.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Gender: female.&#xD;
&#xD;
          -  Age: 18-45 years at the time of signing consent.&#xD;
&#xD;
          -  Clinical or surgical diagnosis of endometriosis undergoing laparoscopy.&#xD;
&#xD;
          -  Controls may not have clinical or surgical diagnosis of endometriosis.&#xD;
&#xD;
          -  Regular menstrual cycles.&#xD;
&#xD;
          -  BMI between 18-40 kg/m2.&#xD;
&#xD;
          -  Sexually active or have had a previous vaginal exam that used a speculum.&#xD;
&#xD;
          -  English speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of any kind of steroidal therapy including oral contraceptives, Norplant, estrogen&#xD;
             replacement/supplemental therapy, androgens (Danazol, Cyclomen, Danocrine,&#xD;
             testosterone) or progesterone. She may not be taking or be on Celebrex.&#xD;
&#xD;
          -  Pregnant.&#xD;
&#xD;
          -  Presence of pelvic infection.&#xD;
&#xD;
          -  Mullerian anomalies with absence of a cervix.&#xD;
&#xD;
          -  History of cancer of the reproductive tract.&#xD;
&#xD;
          -  Presence of undiagnosed uterine bleeding.&#xD;
&#xD;
          -  Treatment with intrauterine device (IUD) or progestin-containing intrauterine device.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>James Segars, MD, FACOG</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>James Segars, MD, FACOG</last_name>
    <phone>410-614-2000</phone>
    <email>jsegars2@jhmi.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bhuchitra Singh, MD, MPH, MS</last_name>
    <phone>410-955-6771</phone>
    <email>bsingh10@jhmi.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Yale School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hugh Taylor, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Luisa Coraluzzi, BSN</last_name>
      <phone>203-785-2164</phone>
      <email>luisa.coraluzzi@yale.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21218</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ie Ming Shih, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tian-Li Wang, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria Facadio Antero, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bhuchitra Singh, MD, MPH, MS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kaylon Bruner-Tran, PhD</last_name>
    </contact>
    <contact_backup>
      <last_name>Kevin Osteen, PhD</last_name>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Endometriosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometriosis</mesh_term>
    <mesh_term>Uterine Diseases</mesh_term>
  </condition_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/NCT03756480
org study id: IRB00188129
secondary id: R01HD096147
nct id: NCT03756480
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will test the hypothesis that the molecular changes present in ectopic
      endometriosis lesions correlate with progesterone-resistant disease (using the criteria
      defined in this study) and are present in matched eutopic endometrium.
Tissues from 100 patients with endometriosis will be analyzed with droplet digital PCR
      (ddPCR) targeted sequencing and responders (n=50) will be compared to non-responders (n=50)
      after controlling confounding factors.

      From a subset of the 100 cases, whole exome sequencing (WES) and Methylation-Specific PCR
      (MSP)-based methylation profiling on microdissected epithelium and stroma will be performed
      in matched eutopic and ectopic tissues from 20 patients with known cancer-associated
      mutations or 20 controls.
observational model: Case-Control
time perspective: Prospective
measure: Number of somatic cancer driver mutations in progesterone-resistant versus progesterone-sensitive endometriosis lesions.
time frame: Six month
description: Digital droplet PCR will be used to identify somatic cancer-driver mutations with the presence of at least one of KRAS or ARID1A or PIK3CA or PPP2R1A cancer-driver mutations to assess any difference between progesterone-resistant endometriosis and progesterone-sensitive endometriosis.
measure: Number of cancer driver mutations in eutopic versus ectopic endometrial tissue in control versus diseased subjects
time frame: Six month
description: Whole exome sequencing in a subset of patients with progesterone-resistant disease and controls will be done using TruSeq Amplicon Cancer Panel (Illumina) to assess the number of cancer driver mutations.
measure: Difference in DNA methylation PCR profile of endometriotic lesions in ectopic versus eutopic endometrium in control versus diseased subjects.
time frame: One month
description: DNA methylation profile of eutopic and ectopic endometrial tissue for cases and controls will be done using Raw Illumina 450K methylation array to assess for any difference.
arm group label: Case Group
description: Clinical or surgical diagnosis of Endometriosis, patients undergoing surgical management
100 participants
arm group label: Control Group
description: No diagnosis of Endometriosis, Patients undergoing Laparoscopic Tubal Ligation
35 participants
Endometrial tissue from ectopic and eutopic sites and blood sample.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
last name: James Segars, MD, FACOG
role: Principal Investigator
affiliation: Professor
last name: James Segars, MD, FACOG
phone: 410-614-2000
email: jsegars2@jhmi.edu
last name: Bhuchitra Singh, MD, MPH, MS
phone: 410-955-6771
email: bsingh10@jhmi.edu
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Endometriosis
mesh term: Uterine Diseases
sharing ipd: No