<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/NCT02201719</url>
  </required_header>
  <id_info>
    <org_study_id>2014/637a</org_study_id>
    <nct_id>NCT02201719</nct_id>
  </id_info>
  <brief_title>Norwegian Adenomyosis Study I</brief_title>
  <acronym>NAPPED I</acronym>
  <official_title>Norwegian Adenomyosis Study: Pathophysiology, Peristalsis, Expression Profiling and Diagnostics, Part I</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Helse Sor-Ost</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oslo University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Adenomyosis is characterized by the appearance of endometrial cells in the muscular layer of&#xD;
      the uterus. It affects about 15-20% of the female population.&#xD;
&#xD;
      The symptoms of adenomyosis are heavy menstrual bleedings and painful menstruation&#xD;
      (dysmenorrhea) and in addition chronic pelvic pain. Subfertility and infertility have been&#xD;
      correlated with adenomyosis.&#xD;
&#xD;
      Parity, age and uterine abrasion increase the risk of adenomyosis. Hormonal factors such as&#xD;
      local hyperestrogenism and elevated levels of prolactin have been identified, but autoimmune&#xD;
      and mechanical factors are also hypothesized.&#xD;
&#xD;
      Regarding treatment, the most effective measure is hysterectomy. As this is a very drastic&#xD;
      measure in younger women, levonogestrel-releasing intrauterine devices, Gonadotropin&#xD;
      releasing hormone (GnRH)-analogues, Danazol, uterine embolization and endometrial ablation&#xD;
      have been tried, but studies are few in number, retrospective, and have small sample sizes.&#xD;
&#xD;
      Adenomyosis has so far not been subject to extensive research efforts. The pathogenesis of&#xD;
      adenomyosis remains still unclear, there are not many satisfying treatment options and&#xD;
      diagnostics include mostly magnetic resonance imaging (MRI) and histology.&#xD;
&#xD;
      The investigators designed a series of 3 studies with a broad approach in understanding&#xD;
      adenomyosis. This is part 1.&#xD;
&#xD;
      NAPPED-1: comparison of 3D-transvaginal ultrasound with MRI and histology in the diagnostic&#xD;
      of adenomyosis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Diagnosis of Adenomyosis with 3D and 2D transvaginal ultrasound. Prospective study of a&#xD;
      consecutive series of 101 patients that are scheduled for hysterectomy and suffer from&#xD;
      bleeding disorders, chronic pelvic pain, dysmenorrhea or dyspareunia. All patients will&#xD;
      undergo transvaginal 2D- ultrasound, 3D-ultrasound and power doppler (PD)-ultrasound (TVU),&#xD;
      magnetic resonance imaging of the pelvic organs (MRI) and hysterectomy.&#xD;
&#xD;
      We will investigate the specificity and sensitivity of 3D and 2D transvaginal ultrasound in&#xD;
      the diagnosis of adenomyosis and compare data with MRI and histopathology, which is the gold&#xD;
      standard by today. In addition, we will collect anamnestic information that might point to&#xD;
      risk factors or connections to prior obstetrical complications and medicine use. In our study&#xD;
      the pathologist will not be blinded to our ultrasound findings, and we want to investigate if&#xD;
      this will raise the sensitivity of histology findings of adenomyosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</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>Difference in sensitivity and specificity of 3D TVU and MRI; in percentage points (%)</measure>
    <time_frame>within 4 weeks after 3D TVU</time_frame>
    <description>Sensitivity and specificity of 3D TVU in the diagnosis of adenomyosis compared to MRI.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Positive and negative predictive value of 3D TVU in percent (%)</measure>
    <time_frame>within 17 weeks after 3D TVU</time_frame>
    <description>Positive and negative predictive value of 3D TVU in diagnosis of adenomyosis. The histological examination is the end-point because it is still regarded to be the gold-standard in diagnosis of adenomyosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in sensitivity and specificity of 3D TVU and 2D TVU; in percentage points (%)</measure>
    <time_frame>within 17 weeks after 3D TVU</time_frame>
    <description>The sensitivity and specificity of 3D TVU in the diagnosis of adenomyosis will also be compared to 2D TVU, in addition to MRI (see primary outcome measure).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in max. thickness of junction zone, in millimeters (mm)</measure>
    <time_frame>post ovulatory in any menstruational cycle prior to surgery, within 4 weeks after 3D TVU</time_frame>
    <description>Compares measurements of junction zone made by 3D TVU and MRI.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of sub- and infertility, percent (%)</measure>
    <time_frame>at time of enrollment</time_frame>
    <description>Questionnaire-based investigation. Prevalence of sub- and infertility in their medical history of the study population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in sensitivity and specificity of 3D TVU and histopathology; in percentage points (%)</measure>
    <time_frame>within 17 weeks after 3D TVU</time_frame>
    <description>The sensitivity and specificity of 3D TVU in the diagnosis of adenomyosis will also be compared to 2D TVU, in addition to MRI (see primary outcome measure) and histopathology, which is still the gold standard.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of miscarriages, in percent (%)</measure>
    <time_frame>at time of enrollment</time_frame>
    <description>Questionnaire-based investigation. Prevalence of miscarriages in the medical history of the study population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of previous gynecological surgeries, in percent (%)</measure>
    <time_frame>at time of enrollment</time_frame>
    <description>Questionnaire-based investigation. Prevalence of previous gynecological surgical interventions in the medical history of the study population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of previous obstetrical complications, in percent (%)</measure>
    <time_frame>menarche to time of enrollment</time_frame>
    <description>Questionnaire-based investigation. Prevalence of previous obstetrical complications in the medical history of the study population.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Adenomyosis</condition>
  <arm_group>
    <arm_group_label>Hysterectomy Adenomyosis</arm_group_label>
    <description>Adenomyosis present</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hysterectomy no adenomyosis</arm_group_label>
    <description>Adenomyosis not present</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Women referred to our clinic and volunteering to participate and that are registrated in&#xD;
        Norway with a norwegian social security number.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Premenopausal women aged 30 - 50 years old&#xD;
&#xD;
          -  scheduled for vaginal, abdominal or laparoscopic total hysterectomy&#xD;
&#xD;
          -  one or more of the following clinical symptoms: bleeding disorders (menorrhagia,&#xD;
             irregular bleeding, hypermenorrhoea), chronic pelvic pain, dysmenorrhoea, or&#xD;
             dyspareunia&#xD;
&#xD;
          -  junction zone definable&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  postmenopausal women,&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  gynecological cancer&#xD;
&#xD;
          -  GnRH analog therapy or systemic hormone therapy in the last three months prior to&#xD;
             hysterectomy&#xD;
&#xD;
          -  junctional zone not identifiable&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marit Lieng, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oslo University Hospital, Ullevål</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Gynecology, Oslo University Hospital Ullevål</name>
      <address>
        <city>Oslo</city>
        <zip>0382</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>July 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>April 4, 2017</last_update_submitted>
  <last_update_submitted_qc>April 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oslo University Hospital</investigator_affiliation>
    <investigator_full_name>Tina Tellum</investigator_full_name>
    <investigator_title>Medical Doctor</investigator_title>
  </responsible_party>
  <keyword>Adenomyosis</keyword>
  <keyword>Dysmenorrhea</keyword>
  <keyword>Chronic pelvic pain</keyword>
  <keyword>Infertility</keyword>
  <keyword>Sensitivity histology</keyword>
  <keyword>womens health</keyword>
  <keyword>junction zone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenomyosis</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/NCT02201719
org study id: 2014/637a
nct id: NCT02201719
lead sponsor: 
collaborator: 
has dmc: Yes
Adenomyosis is characterized by the appearance of endometrial cells in the muscular layer of
      the uterus. It affects about 15-20% of the female population.

      The symptoms of adenomyosis are heavy menstrual bleedings and painful menstruation
      (dysmenorrhea) and in addition chronic pelvic pain. Subfertility and infertility have been
      correlated with adenomyosis.

      Parity, age and uterine abrasion increase the risk of adenomyosis. Hormonal factors such as
      local hyperestrogenism and elevated levels of prolactin have been identified, but autoimmune
      and mechanical factors are also hypothesized.

      Regarding treatment, the most effective measure is hysterectomy. As this is a very drastic
      measure in younger women, levonogestrel-releasing intrauterine devices, Gonadotropin
      releasing hormone (GnRH)-analogues, Danazol, uterine embolization and endometrial ablation
      have been tried, but studies are few in number, retrospective, and have small sample sizes.

      Adenomyosis has so far not been subject to extensive research efforts. The pathogenesis of
      adenomyosis remains still unclear, there are not many satisfying treatment options and
      diagnostics include mostly magnetic resonance imaging (MRI) and histology.

      The investigators designed a series of 3 studies with a broad approach in understanding
      adenomyosis. This is part 1.

      NAPPED-1: comparison of 3D-transvaginal ultrasound with MRI and histology in the diagnostic
      of adenomyosis
Diagnosis of Adenomyosis with 3D and 2D transvaginal ultrasound. Prospective study of a
      consecutive series of 101 patients that are scheduled for hysterectomy and suffer from
      bleeding disorders, chronic pelvic pain, dysmenorrhea or dyspareunia. All patients will
      undergo transvaginal 2D- ultrasound, 3D-ultrasound and power doppler (PD)-ultrasound (TVU),
      magnetic resonance imaging of the pelvic organs (MRI) and hysterectomy.

      We will investigate the specificity and sensitivity of 3D and 2D transvaginal ultrasound in
      the diagnosis of adenomyosis and compare data with MRI and histopathology, which is the gold
      standard by today. In addition, we will collect anamnestic information that might point to
      risk factors or connections to prior obstetrical complications and medicine use. In our study
      the pathologist will not be blinded to our ultrasound findings, and we want to investigate if
      this will raise the sensitivity of histology findings of adenomyosis.
observational model: Case-Control
time perspective: Prospective
measure: Difference in sensitivity and specificity of 3D TVU and MRI; in percentage points (%)
time frame: within 4 weeks after 3D TVU
description: Sensitivity and specificity of 3D TVU in the diagnosis of adenomyosis compared to MRI.
measure: Positive and negative predictive value of 3D TVU in percent (%)
time frame: within 17 weeks after 3D TVU
description: Positive and negative predictive value of 3D TVU in diagnosis of adenomyosis. The histological examination is the end-point because it is still regarded to be the gold-standard in diagnosis of adenomyosis.
measure: Difference in sensitivity and specificity of 3D TVU and 2D TVU; in percentage points (%)
time frame: within 17 weeks after 3D TVU
description: The sensitivity and specificity of 3D TVU in the diagnosis of adenomyosis will also be compared to 2D TVU, in addition to MRI (see primary outcome measure).
measure: Difference in max. thickness of junction zone, in millimeters (mm)
time frame: post ovulatory in any menstruational cycle prior to surgery, within 4 weeks after 3D TVU
description: Compares measurements of junction zone made by 3D TVU and MRI.
measure: Prevalence of sub- and infertility, percent (%)
time frame: at time of enrollment
description: Questionnaire-based investigation. Prevalence of sub- and infertility in their medical history of the study population.
measure: Difference in sensitivity and specificity of 3D TVU and histopathology; in percentage points (%)
time frame: within 17 weeks after 3D TVU
description: The sensitivity and specificity of 3D TVU in the diagnosis of adenomyosis will also be compared to 2D TVU, in addition to MRI (see primary outcome measure) and histopathology, which is still the gold standard.
measure: Prevalence of miscarriages, in percent (%)
time frame: at time of enrollment
description: Questionnaire-based investigation. Prevalence of miscarriages in the medical history of the study population.
measure: Prevalence of previous gynecological surgeries, in percent (%)
time frame: at time of enrollment
description: Questionnaire-based investigation. Prevalence of previous gynecological surgical interventions in the medical history of the study population.
measure: Prevalence of previous obstetrical complications, in percent (%)
time frame: menarche to time of enrollment
description: Questionnaire-based investigation. Prevalence of previous obstetrical complications in the medical history of the study population.
arm group label: Hysterectomy Adenomyosis
description: Adenomyosis present
arm group label: Hysterectomy no adenomyosis
description: Adenomyosis not present
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 25 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marit Lieng, PhD, MD
role: Principal Investigator
affiliation: Oslo University Hospital, Ullevål
facility: 
country: Norway
responsible party type: Principal Investigator
investigator affiliation: Oslo University Hospital
investigator full name: Tina Tellum
investigator title: Medical Doctor
mesh term: Adenomyosis