<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/NCT04401592</url>
  </required_header>
  <id_info>
    <org_study_id>ENDOGAL</org_study_id>
    <nct_id>NCT04401592</nct_id>
  </id_info>
  <brief_title>The Role of Galectins in the Non-invasive Diagnosis of Endometriosis</brief_title>
  <official_title>The Role of Galectin-1,3,9 in the the Non-invasive Diagnosis of Endometriosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Semmelweis University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pecs</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Semmelweis University</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>
      Endometriosis is one of the most common infertility-related gynecologic disorder that affect&#xD;
      approximately 10-15% of women in reproductive age. The main symptoms are chronic pelvic pain,&#xD;
      infertility, dysmenorrhea and dyspareunia. There exists an average diagnostic delay of 7 year&#xD;
      but data widely varies between different countries. The current &quot;gold standard&quot; in the&#xD;
      diagnosis of endometriosis remains a laparoscopy. Since laparoscopy is an invasive surgical&#xD;
      procedure with its potential risk, the development of a non-invasive laboratory test would be&#xD;
      of great benefit in the early, clinical management of this diseaseIn the past few years,&#xD;
      lectins have become the focus of reproductive immunology, inflammation and autoimmunity.&#xD;
      Galectins (Gal) are beta-galactoside binding lectins that play a key role in the regulation&#xD;
      of the immune system, cell growth, adhesion, apoptosis, and angiogenesis. Until now 13&#xD;
      different types of galectins have been found in humans, among them Gal-1-4, 7-9 and 12 were&#xD;
      detected in the normal endometrium. So far only Gal-1 and Gal-3 have been studied in relation&#xD;
      to endometriosis. In a recent pilot study, the investigators have shown that Gal-9 levels are&#xD;
      significantly elevated in the serum of endometriosis patients compared to healthy controls.&#xD;
      Gal-9 had a high sensitivity (94%) and specificity (93,75%), indicating better diagnostic&#xD;
      potential than that of other endometriosis biomarkers and of surgery as the current gold&#xD;
      standard.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Endometriosis is one of the most common infertility-related gynecologic disorder that affect&#xD;
      approximately 10-15% of women in reproductive age. The main symptoms are chronic pelvic pain,&#xD;
      infertility, dysmenorrhea and dyspareunia. The etiology and pathogenesis of endometriosis has&#xD;
      been widely investigated over the past 30 years. Although there are several concepts trying&#xD;
      to explain its development, but none of them can be applied for all types of the disease.&#xD;
&#xD;
      The peak incidence of the diagnosis of endometriosis lies between the ages of 25 to 34,&#xD;
      although symptoms mostly develop much earlier. There exists an average diagnostic delay of 7&#xD;
      year but data widely varies between different countries: in the is UK 7.9 years, in the US&#xD;
      11.7 years, in Germany and Austria 7 years, in Spain 8 years, in Norway 6.7 years, in Ireland&#xD;
      and Belgium 5 years and in Hungary 3.9 years. Such a diagnostic delay is multifactorial, but&#xD;
      most importantly due to the lack of non-invasive diagnosis.&#xD;
&#xD;
      The current &quot;gold standard&quot; in the diagnosis of endometriosis remains a laparoscopy with a&#xD;
      sensitivity of 79% and a specificity of 94%. Since laparoscopy is an invasive surgical&#xD;
      procedure with its potential risk, the development of a non-invasive laboratory test would be&#xD;
      of great benefit in the early, clinical management of this disease. Such a biomarker has the&#xD;
      enormous potential to improve quality of life, reduce the risks to the patient and the&#xD;
      enormous costs to society related to endometriosis.&#xD;
&#xD;
      Until now, several molecules involved in the pathogenesis of endometriosis were investigated&#xD;
      as a potential biomarker, however the majority of them have proven inadequate for the&#xD;
      diagnosis. In the past few years, lectins have become the focus of reproductive immunology,&#xD;
      inflammation and autoimmunity. Galectins (Gal) are beta-galactoside binding lectins that play&#xD;
      a key role in the regulation of the immune system, cell growth, adhesion, apoptosis, and&#xD;
      angiogenesis. Until now 13 different types of galectins have been found in humans, among them&#xD;
      Gal-1-4, 7-9 and 12 were detected in the normal endometrium. So far only Gal-1 and Gal-3 have&#xD;
      been studied in relation to endometriosis. It was reported that Gal-1 had a cycle-dependent&#xD;
      expression in normal endometrial stromal cells, and its production was significantly elevated&#xD;
      in the early pregnancy decidua. In relation to endometriosis, Gal-1 was found to be more&#xD;
      abundantly expressed in ectopic endometriotic lesions when compared with the eutopic tissues.&#xD;
      Furthermore, the eutopic endometrium of the affected patients showed higher Gal-1 expression&#xD;
      than its normal counterparts. In addition to this, similar to Gal-1, Gal-3 was overexpressed&#xD;
      in various forms of endometriosis as well as in the eutopic endometrium of diseased women.&#xD;
&#xD;
      The investigators have previously shown that Gal-9 mRNA was markedly overexpressed in the&#xD;
      eutopic endometrium of patients with endometriosis in comparison with healthy controls. In&#xD;
      addition, the investigators results showed that besides the eutopic endometrium, Gal-9 was&#xD;
      also expressed in ectopic implants regardless of the localization of the lesions. The&#xD;
      investigators have determined that Gal-9 levels are significantly elevated in the serum of&#xD;
      endometriosis patients compared to healthy controls. Gal-9 has a high sensitivity (94%) and&#xD;
      specificity (93,75%), indicating better diagnostic potential than that of other endometriosis&#xD;
      biomarkers. The optimal cutoff point estimated from the Youden's index was 132 pg/mL, with a&#xD;
      sensitivity of 94% and specificity of 93.75%. Using this threshold, the positive predictive&#xD;
      value was 97.92% and the negative predictive value was 83.33%, with a prevalence of 75.76%.&#xD;
      The diagnostic accuracy of this test was 93.94%, indicating better diagnostic potential than&#xD;
      that other already published serum biomarkers.&#xD;
&#xD;
      Based on this previous results, the investigators suggest that Gal-9 is produced by ectopic&#xD;
      endometriotic implants, the investigators would like to determine the serum Gal-9 levels one&#xD;
      day before and after the surgery and at least 1-6 months later. The investigators aim is to&#xD;
      examine the serum Gal-1 and Gal-3 levels in endometriosis patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">September 1, 2021</start_date>
  <completion_date type="Anticipated">September 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2022</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>Development of new non-invasive biomarker for endometriosis</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Endometriosis</condition>
  <condition>Endometriosis Ovary</condition>
  <condition>Endometriosis Rectovaginal Septum</condition>
  <arm_group>
    <arm_group_label>disease and control</arm_group_label>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        in reproductive age laporoscopically proved endometriosis&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Histologically proved endometriosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Previous or current hormone therapy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Women in reproductive age</gender_description>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>48 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <reference>
    <citation>Brubel R, Bokor A, Pohl A, Schilli GK, Szereday L, Bacher-Szamuel R, Rigo J Jr, Polgar B. Serum galectin-9 as a noninvasive biomarker for the detection of endometriosis and pelvic pain or infertility-related gynecologic disorders. Fertil Steril. 2017 Dec;108(6):1016-1025.e2. doi: 10.1016/j.fertnstert.2017.09.008.</citation>
    <PMID>29202955</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>April 12, 2021</last_update_submitted>
  <last_update_submitted_qc>April 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Semmelweis University</investigator_affiliation>
    <investigator_full_name>Reka Brubel</investigator_full_name>
    <investigator_title>MD PhD</investigator_title>
  </responsible_party>
  <keyword>Endometriosis</keyword>
  <keyword>Biomarker</keyword>
  <keyword>Non-invasive diagnosis</keyword>
  <keyword>Galectins</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometriosis</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/NCT04401592
org study id: ENDOGAL
nct id: NCT04401592
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Endometriosis is one of the most common infertility-related gynecologic disorder that affect
      approximately 10-15% of women in reproductive age. The main symptoms are chronic pelvic pain,
      infertility, dysmenorrhea and dyspareunia. There exists an average diagnostic delay of 7 year
      but data widely varies between different countries. The current "gold standard" in the
      diagnosis of endometriosis remains a laparoscopy. Since laparoscopy is an invasive surgical
      procedure with its potential risk, the development of a non-invasive laboratory test would be
      of great benefit in the early, clinical management of this diseaseIn the past few years,
      lectins have become the focus of reproductive immunology, inflammation and autoimmunity.
      Galectins (Gal) are beta-galactoside binding lectins that play a key role in the regulation
      of the immune system, cell growth, adhesion, apoptosis, and angiogenesis. Until now 13
      different types of galectins have been found in humans, among them Gal-1-4, 7-9 and 12 were
      detected in the normal endometrium. So far only Gal-1 and Gal-3 have been studied in relation
      to endometriosis. In a recent pilot study, the investigators have shown that Gal-9 levels are
      significantly elevated in the serum of endometriosis patients compared to healthy controls.
      Gal-9 had a high sensitivity (94%) and specificity (93,75%), indicating better diagnostic
      potential than that of other endometriosis biomarkers and of surgery as the current gold
      standard.
Endometriosis is one of the most common infertility-related gynecologic disorder that affect
      approximately 10-15% of women in reproductive age. The main symptoms are chronic pelvic pain,
      infertility, dysmenorrhea and dyspareunia. The etiology and pathogenesis of endometriosis has
      been widely investigated over the past 30 years. Although there are several concepts trying
      to explain its development, but none of them can be applied for all types of the disease.

      The peak incidence of the diagnosis of endometriosis lies between the ages of 25 to 34,
      although symptoms mostly develop much earlier. There exists an average diagnostic delay of 7
      year but data widely varies between different countries: in the is UK 7.9 years, in the US
      11.7 years, in Germany and Austria 7 years, in Spain 8 years, in Norway 6.7 years, in Ireland
      and Belgium 5 years and in Hungary 3.9 years. Such a diagnostic delay is multifactorial, but
      most importantly due to the lack of non-invasive diagnosis.

      The current "gold standard" in the diagnosis of endometriosis remains a laparoscopy with a
      sensitivity of 79% and a specificity of 94%. Since laparoscopy is an invasive surgical
      procedure with its potential risk, the development of a non-invasive laboratory test would be
      of great benefit in the early, clinical management of this disease. Such a biomarker has the
      enormous potential to improve quality of life, reduce the risks to the patient and the
      enormous costs to society related to endometriosis.

      Until now, several molecules involved in the pathogenesis of endometriosis were investigated
      as a potential biomarker, however the majority of them have proven inadequate for the
      diagnosis. In the past few years, lectins have become the focus of reproductive immunology,
      inflammation and autoimmunity. Galectins (Gal) are beta-galactoside binding lectins that play
      a key role in the regulation of the immune system, cell growth, adhesion, apoptosis, and
      angiogenesis. Until now 13 different types of galectins have been found in humans, among them
      Gal-1-4, 7-9 and 12 were detected in the normal endometrium. So far only Gal-1 and Gal-3 have
      been studied in relation to endometriosis. It was reported that Gal-1 had a cycle-dependent
      expression in normal endometrial stromal cells, and its production was significantly elevated
      in the early pregnancy decidua. In relation to endometriosis, Gal-1 was found to be more
      abundantly expressed in ectopic endometriotic lesions when compared with the eutopic tissues.
      Furthermore, the eutopic endometrium of the affected patients showed higher Gal-1 expression
      than its normal counterparts. In addition to this, similar to Gal-1, Gal-3 was overexpressed
      in various forms of endometriosis as well as in the eutopic endometrium of diseased women.

      The investigators have previously shown that Gal-9 mRNA was markedly overexpressed in the
      eutopic endometrium of patients with endometriosis in comparison with healthy controls. In
      addition, the investigators results showed that besides the eutopic endometrium, Gal-9 was
      also expressed in ectopic implants regardless of the localization of the lesions. The
      investigators have determined that Gal-9 levels are significantly elevated in the serum of
      endometriosis patients compared to healthy controls. Gal-9 has a high sensitivity (94%) and
      specificity (93,75%), indicating better diagnostic potential than that of other endometriosis
      biomarkers. The optimal cutoff point estimated from the Youden's index was 132 pg/mL, with a
      sensitivity of 94% and specificity of 93.75%. Using this threshold, the positive predictive
      value was 97.92% and the negative predictive value was 83.33%, with a prevalence of 75.76%.
      The diagnostic accuracy of this test was 93.94%, indicating better diagnostic potential than
      that other already published serum biomarkers.

      Based on this previous results, the investigators suggest that Gal-9 is produced by ectopic
      endometriotic implants, the investigators would like to determine the serum Gal-9 levels one
      day before and after the surgery and at least 1-6 months later. The investigators aim is to
      examine the serum Gal-1 and Gal-3 levels in endometriosis patients.
observational model: Case-Control
time perspective: Prospective
measure: Development of new non-invasive biomarker for endometriosis
time frame: 24 months
arm group label: disease and control
Serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Women in reproductive age
minimum age: 20 Years
maximum age: 48 Years
healthy volunteers: Accepts Healthy Volunteers
citation: Brubel R, Bokor A, Pohl A, Schilli GK, Szereday L, Bacher-Szamuel R, Rigo J Jr, Polgar B. Serum galectin-9 as a noninvasive biomarker for the detection of endometriosis and pelvic pain or infertility-related gynecologic disorders. Fertil Steril. 2017 Dec;108(6):1016-1025.e2. doi: 10.1016/j.fertnstert.2017.09.008.
PMID: 29202955
responsible party type: Principal Investigator
investigator affiliation: Semmelweis University
investigator full name: Reka Brubel
investigator title: MD PhD
mesh term: Endometriosis
sharing ipd: No