<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/NCT04426760</url>
  </required_header>
  <id_info>
    <org_study_id>2017/9703</org_study_id>
    <nct_id>NCT04426760</nct_id>
  </id_info>
  <brief_title>Fibroids and Infertility - a Study of the Significance of Removal of Fibroids With Regard to Endometrial Receptivity</brief_title>
  <acronym>FIN</acronym>
  <official_title>Mechanisms of Reduced Fertility in Women With Uterine Leiomyomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oslo University Hospital</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>
      We aim to explore some of the molecular factors that reduce fertility for women with&#xD;
      leiomyomas, taking into account leiomyoma location, size, number and vascularity. Tissue&#xD;
      samples from the endometrium and leiomyomas will be obtained during the mid secretory phase&#xD;
      before and 3-6 months after surgical excision for a comprehensive search for key molecular&#xD;
      derangements.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Baseline medical information and standard questionnaire to record symptoms are collected from&#xD;
      all participants and a gynaecological examination and a 2D and 3D vaginal ultrasonography&#xD;
      including saline infusion sonography (SIS), if indicated, are performed. Blood samples for&#xD;
      the biobank for extraction of germ line DNA and for identification of possible biomarkers are&#xD;
      taken.&#xD;
&#xD;
      The women with submucosal leiomyomas will undergo hysteroscopic myomectomy and the women with&#xD;
      intramural leiomyomas will undergo myomectomy per laparoscopy or laparotomy.&#xD;
&#xD;
      For the participants with intramural leiomyomas and the fertile/infertile controls,&#xD;
      endometrial samples are taken with an endometrial suction curette in an outpatient setting at&#xD;
      day 19-23 of the menstrual cycle. The endometrial sampling in the group of women with&#xD;
      submucosal leiomyomas is being done during the hysteroscopic removal of the leiomyoma, also&#xD;
      at day 19-23 of the menstrual cycle.&#xD;
&#xD;
      3-6 months after surgery, cycle day 19-23, endometrial samples will be taken from the women&#xD;
      who have undergone myomectomy and ultrasound examination is being performed. The women with&#xD;
      submucosal leiomyomas will undergo a second look hysteroscopy&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">September 15, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 15, 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>2 Years</target_duration>
  <primary_outcome>
    <measure>HOXA 10 expression</measure>
    <time_frame>3-6 months</time_frame>
    <description>Fold change of HOXA 10 Expression 3-6 months after myomectomy compared to pre-surgery Levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Expression of other molecular markers</measure>
    <time_frame>3-6 months</time_frame>
    <description>Fold change of other molecular markers than HOXA 10 of endometrial receptivity 3-6 months after myomectomy and compared to fertile/infertile controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endometrial vascular pattern</measure>
    <time_frame>3-6 months</time_frame>
    <description>VI and FI of the endometrium and subendometrial myometrium of women with leimyomas 3-6 months after myomectomy and compared to fertile/infertile controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular characteristics of leiomyomas</measure>
    <time_frame>3-6 months</time_frame>
    <description>Vascular characteristics of leiomyomas associated with endometrial changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leiomyoma size</measure>
    <time_frame>3-6 months</time_frame>
    <description>Leiomyomas size in centimeters associated with endometrial changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Leiomyoma location</measure>
    <time_frame>3-6 months</time_frame>
    <description>Leiomyoma location associated with endometrial changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genomic characteristics</measure>
    <time_frame>3-6 months</time_frame>
    <description>Genomic characteristics of leiomyomas associated with endometrial changes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Scar formation</measure>
    <time_frame>3-6 months</time_frame>
    <description>Scar/fibrosis/adhesion formation after myomectomy; macroscopically and histologically</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy</measure>
    <time_frame>2 years</time_frame>
    <description>Pregnancy and deliveries within 2 years after myomectomy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HOXA10 in endometrium of women with leiomyomas compared to fertile/infertile controls</measure>
    <time_frame>3-6 months</time_frame>
    <description>Difference in HOXA 10 expression in endometrium of women with leiomyomas compared to fertile/infertile controls</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression of molecular markers adjacent to the leiomyoma versus remote from the leiomyoma</measure>
    <time_frame>3-6 months</time_frame>
    <description>Difference in expression of molecular markers in endometrium adjacent to the leiomyoma compared to endometrium remote from the leiomyoma.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Partially resected leiomyomas</measure>
    <time_frame>3-6 months</time_frame>
    <description>Alterations in molecular markers of endometrial receptivity after partially resected submucosal leiomyomas.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Submucosal leiomyomas versus intramural leiomyomas</measure>
    <time_frame>3-6 months</time_frame>
    <description>Difference in expression of molecular markers in endometrium of women with submucosal leiomyomas compared with endometrium in women with intramural leiomyomas.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers in blood</measure>
    <time_frame>1 year</time_frame>
    <description>Biomarkers in blood related to leiomyomas and a possible correlation between certain biomarkers and reduced endometrial receptivity.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Leiomyoma, Uterine</condition>
  <arm_group>
    <arm_group_label>Women with submucosal leiomyoma(s)</arm_group_label>
    <description>Women with submucosal leimyomas undergoing hysteroscopical removal of the leiomyoma</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Women with intramural leiomyomas</arm_group_label>
    <description>Women with intramural leiomyomas undergoing myomectomy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Infertility patients</arm_group_label>
    <description>Patients treated at the Department for Reproductive Medicine at the Oslo University hospital failing to conceive after 3 or more embryo transfers with good quality embryos.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fertile women</arm_group_label>
    <description>Healthy, volunteering women with proved fertility with 1 or more deliveries and no history of infertility</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transcervical resection of fibroids</intervention_name>
    <description>Transcervical resection of fibroids</description>
    <arm_group_label>Women with submucosal leiomyoma(s)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Myomectomy per laparoscopy or laparotomy</intervention_name>
    <description>Myomectomy per laparoscopy or laparotomy</description>
    <arm_group_label>Women with intramural leiomyomas</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Endometrial biopsies Leiomyoma biopsy Serum Plasma Blood cells&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients referred to the Department of Gynaecology at Oslo University Hospital for&#xD;
        treatment of submucosal or intramural leiomyomas.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: 18 to 40 years&#xD;
&#xD;
          -  Presence of leiomyoma(s)&#xD;
&#xD;
          -  Regular menstrual cycle (28 +/- 7 days)&#xD;
&#xD;
          -  Having had at least 2 normal menstrual cycles after ending the treatment if previously&#xD;
             treated with GnRH analogue&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  No treatment indication (no symptoms and/or no desire for fertility)&#xD;
&#xD;
          -  Contraindication for surgery&#xD;
&#xD;
          -  Known endometriosis&#xD;
&#xD;
          -  Known PCOS&#xD;
&#xD;
          -  Untreated hydrosalpinx&#xD;
&#xD;
          -  Malignancy; gynaecological or other location&#xD;
&#xD;
          -  Pre-malignant or malignant pap smear or endometrial biopsy&#xD;
&#xD;
          -  Hormonal treatment including ulipristal acetat and levonorgestrel intrauterine device&#xD;
             last three months before inclusion in the study&#xD;
&#xD;
          -  Ongoing treatment with GnRH analogue&#xD;
&#xD;
          -  Pregnancy last 3 months&#xD;
&#xD;
          -  Ongoing lactation&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>The biological sex must be female since we are studying a phenomenone occuring in the female genital tract.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Thea F. Mikkelsen, MD</last_name>
    <phone>004797612934</phone>
    <email>themik@ous-hf.no</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kirsten Hald, PhD</last_name>
    <phone>004795224181</phone>
    <email>UXKILD@ous-hf.no</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thea F Mikkelsen, MD</last_name>
      <phone>004797612934</phone>
      <email>themik@ous-hf.no</email>
    </contact>
    <contact_backup>
      <last_name>Kirsten Hald, PhD</last_name>
      <phone>004795224181</phone>
      <email>UXKILD@ous-hf.no</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 8, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 8, 2020</last_update_submitted>
  <last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oslo University Hospital</investigator_affiliation>
    <investigator_full_name>Kirsten Hald, MD, PhD</investigator_full_name>
    <investigator_title>Senior Consultant</investigator_title>
  </responsible_party>
  <keyword>Infertility</keyword>
  <keyword>Endometrial receptivity</keyword>
  <keyword>Leiomyoma</keyword>
  <keyword>Fibroid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leiomyoma</mesh_term>
    <mesh_term>Myofibroma</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/NCT04426760
org study id: 2017/9703
nct id: NCT04426760
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
We aim to explore some of the molecular factors that reduce fertility for women with
      leiomyomas, taking into account leiomyoma location, size, number and vascularity. Tissue
      samples from the endometrium and leiomyomas will be obtained during the mid secretory phase
      before and 3-6 months after surgical excision for a comprehensive search for key molecular
      derangements.
Baseline medical information and standard questionnaire to record symptoms are collected from
      all participants and a gynaecological examination and a 2D and 3D vaginal ultrasonography
      including saline infusion sonography (SIS), if indicated, are performed. Blood samples for
      the biobank for extraction of germ line DNA and for identification of possible biomarkers are
      taken.

      The women with submucosal leiomyomas will undergo hysteroscopic myomectomy and the women with
      intramural leiomyomas will undergo myomectomy per laparoscopy or laparotomy.

      For the participants with intramural leiomyomas and the fertile/infertile controls,
      endometrial samples are taken with an endometrial suction curette in an outpatient setting at
      day 19-23 of the menstrual cycle. The endometrial sampling in the group of women with
      submucosal leiomyomas is being done during the hysteroscopic removal of the leiomyoma, also
      at day 19-23 of the menstrual cycle.

      3-6 months after surgery, cycle day 19-23, endometrial samples will be taken from the women
      who have undergone myomectomy and ultrasound examination is being performed. The women with
      submucosal leiomyomas will undergo a second look hysteroscopy
observational model: Case-Only
time perspective: Prospective
measure: HOXA 10 expression
time frame: 3-6 months
description: Fold change of HOXA 10 Expression 3-6 months after myomectomy compared to pre-surgery Levels
measure: Expression of other molecular markers
time frame: 3-6 months
description: Fold change of other molecular markers than HOXA 10 of endometrial receptivity 3-6 months after myomectomy and compared to fertile/infertile controls
measure: Endometrial vascular pattern
time frame: 3-6 months
description: VI and FI of the endometrium and subendometrial myometrium of women with leimyomas 3-6 months after myomectomy and compared to fertile/infertile controls
measure: Vascular characteristics of leiomyomas
time frame: 3-6 months
description: Vascular characteristics of leiomyomas associated with endometrial changes
measure: Leiomyoma size
time frame: 3-6 months
description: Leiomyomas size in centimeters associated with endometrial changes
measure: Leiomyoma location
time frame: 3-6 months
description: Leiomyoma location associated with endometrial changes
measure: Genomic characteristics
time frame: 3-6 months
description: Genomic characteristics of leiomyomas associated with endometrial changes
measure: Scar formation
time frame: 3-6 months
description: Scar/fibrosis/adhesion formation after myomectomy; macroscopically and histologically
measure: Pregnancy
time frame: 2 years
description: Pregnancy and deliveries within 2 years after myomectomy.
measure: HOXA10 in endometrium of women with leiomyomas compared to fertile/infertile controls
time frame: 3-6 months
description: Difference in HOXA 10 expression in endometrium of women with leiomyomas compared to fertile/infertile controls
measure: Expression of molecular markers adjacent to the leiomyoma versus remote from the leiomyoma
time frame: 3-6 months
description: Difference in expression of molecular markers in endometrium adjacent to the leiomyoma compared to endometrium remote from the leiomyoma.
measure: Partially resected leiomyomas
time frame: 3-6 months
description: Alterations in molecular markers of endometrial receptivity after partially resected submucosal leiomyomas.
measure: Submucosal leiomyomas versus intramural leiomyomas
time frame: 3-6 months
description: Difference in expression of molecular markers in endometrium of women with submucosal leiomyomas compared with endometrium in women with intramural leiomyomas.
measure: Biomarkers in blood
time frame: 1 year
description: Biomarkers in blood related to leiomyomas and a possible correlation between certain biomarkers and reduced endometrial receptivity.
arm group label: Women with submucosal leiomyoma(s)
description: Women with submucosal leimyomas undergoing hysteroscopical removal of the leiomyoma
arm group label: Women with intramural leiomyomas
description: Women with intramural leiomyomas undergoing myomectomy
arm group label: Infertility patients
description: Patients treated at the Department for Reproductive Medicine at the Oslo University hospital failing to conceive after 3 or more embryo transfers with good quality embryos.
arm group label: Fertile women
description: Healthy, volunteering women with proved fertility with 1 or more deliveries and no history of infertility
intervention type: Procedure
intervention name: Transcervical resection of fibroids
description: Transcervical resection of fibroids
arm group label: Women with submucosal leiomyoma(s)
intervention type: Procedure
intervention name: Myomectomy per laparoscopy or laparotomy
description: Myomectomy per laparoscopy or laparotomy
arm group label: Women with intramural leiomyomas
Endometrial biopsies Leiomyoma biopsy Serum Plasma Blood cells
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: The biological sex must be female since we are studying a phenomenone occuring in the female genital tract.
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Thea F. Mikkelsen, MD
phone: 004797612934
email: themik@ous-hf.no
last name: Kirsten Hald, PhD
phone: 004795224181
email: UXKILD@ous-hf.no
facility: 
status: Recruiting
contact: 
contact backup: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Oslo University Hospital
investigator full name: Kirsten Hald, MD, PhD
investigator title: Senior Consultant
mesh term: Leiomyoma
mesh term: Myofibroma