<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/NCT04493983</url>
  </required_header>
  <id_info>
    <org_study_id>7-11/62</org_study_id>
    <nct_id>NCT04493983</nct_id>
  </id_info>
  <brief_title>Role of Oxidative Stress in Ovarian Tissue After CO2-pneumoperitoneum Application-induced I/R</brief_title>
  <official_title>Evaluation of Oxidative Stress-related Biomarkers With a Histopathological and Biochemical Approach in Ovarian Tissue From a Human Carbondioxide Pneumoperitoneum-applied Ischemia/Reperfusion Model</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ismet Hortu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ege University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Because of cellular changes in response to ischemia and a following period of reperfusion,&#xD;
      damages to organs and different tissues occur. There are several ongoing studies to enlighten&#xD;
      the pathophysiological processes underlying these damages inflicted by ischemia/reperfusion.&#xD;
&#xD;
      Gases (CO2) with low water content are used in pneumoperitoneum, which is a procedure to&#xD;
      inflate the abdominal cavity with an appropriate gas for laparoscopic operations. In the&#xD;
      current literature, it was shown that due to a restricted blood flow during the gas&#xD;
      insufflation, ischemia develops and with the reperfusion of the organ in deflation period,&#xD;
      oxidative stress and inflammation increases, leading to ischemia/reperfusion-related organ&#xD;
      and tissue damages.&#xD;
&#xD;
      In the proposed study, biomarkers for ischemia/reperfusion-inflicted damage will be evaluated&#xD;
      in a biochemical and histopathological perspective in biopsy samples of ovaries from a young&#xD;
      patient group in which hysterectomy and bilateral salpingo-oophorectomy will be performed,&#xD;
      laparoscopically.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the laparoscopic salpingo-oophorectomy, after the induction of anesthesia, an umbilical&#xD;
      skin incision was performed. Pneumoperitoneum was established using dry, nonheated CO2&#xD;
      insufflation through a Veress needle. A 10-mm trocar was inserted into the abdominal cavity&#xD;
      through the umbilical incision for the laparoscope. Subsequently, three 5-mm ancillary&#xD;
      trocars, 2 on the lower abdominal quadrants and 1 on the left upper quadrant, were introduced&#xD;
      to the abdominal space under direct optic visualization. IAP was set at 14 mm Hg and&#xD;
      maintained with a gas insufflator (Endoflator; Karl Storz Endoscopy, Tuttlingen,&#xD;
      Germany)Immediately after the port placement, unilateral oophorectomy was performed, and&#xD;
      ovarian biopsies were obtained. The operation continued with ligation and transection of the&#xD;
      contralateral utero-ovarian ligament and the bilateral round ligaments. The contralateral&#xD;
      infundibulopelvic ligament, which contains the main vascular supply for the contralateral&#xD;
      ovary, remained intact. Subsequently, anterior and posterior leaflets of the broad ligament&#xD;
      were identified and dissected, and the bladder was placed away from the lower uterine&#xD;
      segment. The uterus removed from vaginal way after necessary steps. After desufflation, the&#xD;
      cuff closure procedure was performed vaginally. At the end of the closure, pneumoperitoneum&#xD;
      was reestablished, the remaining contralateral ovary was removed immediately, and biopsies&#xD;
      were obtained for histologic analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Actual">September 1, 2020</completion_date>
  <primary_completion_date type="Actual">September 1, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Impact of CO2 pneumoperitoneum on ovaries by comparing histopathology</measure>
    <time_frame>1-day (at the time of the surgery)</time_frame>
    <description>Histopathological investigation of ovaries after CO2 pneumoperitoneum -induced I/R</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Oophorectomy</condition>
  <condition>Oxidative Stress</condition>
  <condition>Ischemia Reperfusion Injury</condition>
  <arm_group>
    <arm_group_label>Investigation</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Unilateral oophorectomy was performed immediately after abdominal entry, and the remaining contralateral ovary was excised at the end of the hysterectomy in order to compare the effect of these surgical procedures on ovarian tissue.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>laparoscopic salpingo-oophorectomy</intervention_name>
    <description>Laparoscopic bilateral salpingo-oophorectomy</description>
    <arm_group_label>Investigation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Laparoscopic bilateral salpingo-oophorectomy</intervention_name>
    <description>Unilateral oophorectomy was performed immediately after abdominal entry, and the remaining contralateral ovary was excised at the end of the hysterectomy in order to compare the effect of these surgical procedures on ovarian tissue.</description>
    <arm_group_label>Investigation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Transgender Men who wants to remove their uterus and both ovaries.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known endometriosis&#xD;
&#xD;
          -  Hysterectomized patient&#xD;
&#xD;
          -  Unacceptance to involve to the trial&#xD;
&#xD;
          -  Suspicion of malignancy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ege University School of Medicine, Department of Obstetrics and Gynecology</name>
      <address>
        <city>Izmir</city>
        <zip>35100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <results_reference>
    <citation>Guven S, Muci E, Unsal MA, Yulug E, Alver A, Kadioglu Duman M, Mentese A. The effects of carbon dioxide pneumoperitoneum on ovarian blood flow, oxidative stress markers, and morphology during laparoscopy: a rabbit model. Fertil Steril. 2010 Mar 1;93(4):1327-32. doi: 10.1016/j.fertnstert.2008.10.053. Epub 2008 Dec 9.</citation>
    <PMID>19081089</PMID>
  </results_reference>
  <results_reference>
    <citation>Schafer M, Krahenbuhl L. Effect of laparoscopy on intra-abdominal blood flow. Surgery. 2001 Apr;129(4):385-9. doi: 10.1067/msy.2001.110224. No abstract available.</citation>
    <PMID>11283527</PMID>
  </results_reference>
  <results_reference>
    <citation>Cevrioglu AS, Yilmaz S, Koken T, Tokyol C, Yilmazer M, Fenkci IV. Comparison of the effects of low intra-abdominal pressure and ischaemic preconditioning on the generation of oxidative stress markers and inflammatory cytokines during laparoscopy in rats. Hum Reprod. 2004 Sep;19(9):2144-51. doi: 10.1093/humrep/deh380. Epub 2004 Jun 30.</citation>
    <PMID>15229201</PMID>
  </results_reference>
  <results_reference>
    <citation>Biler A, Yucebilgin S, Sendag F, Akman L, Akdemir A, Ates U, Uyanikgil Y, Yilmaz-Dilsiz O, Sezer E. The effects of different intraabdominal pressure protocols in laparoscopic procedures on oxidative stress markers and morphology in rat ovaries. Adv Clin Exp Med. 2014 Nov-Dec;23(6):885-92. doi: 10.17219/acem/37331.</citation>
    <PMID>25618113</PMID>
  </results_reference>
  <results_reference>
    <citation>Akdemir A, Taylan E, Sahin C, Ozgurel B, Karlitepe A, Zekioglu O, Ercan G. The Impact of Carbon Dioxide Pneumoperitoneum on Ovarian Ischemia-Reperfusion Injury during Laparoscopic Surgery: A Preliminary Study. J Minim Invasive Gynecol. 2018 May-Jun;25(4):638-643. doi: 10.1016/j.jmig.2017.10.018. Epub 2017 Nov 28.</citation>
    <PMID>29107119</PMID>
  </results_reference>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>May 23, 2021</last_update_submitted>
  <last_update_submitted_qc>May 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ege University</investigator_affiliation>
    <investigator_full_name>Ismet Hortu</investigator_full_name>
    <investigator_title>Clinical researcher, Ismet Hortu, MD., PhD. Department of Obstetrics and Gynecology, Ege University School of Medicine, Izmir, Turkey</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumoperitoneum</mesh_term>
    <mesh_term>Reperfusion Injury</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04493983
org study id: 7-11/62
nct id: NCT04493983
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Because of cellular changes in response to ischemia and a following period of reperfusion,
      damages to organs and different tissues occur. There are several ongoing studies to enlighten
      the pathophysiological processes underlying these damages inflicted by ischemia/reperfusion.

      Gases (CO2) with low water content are used in pneumoperitoneum, which is a procedure to
      inflate the abdominal cavity with an appropriate gas for laparoscopic operations. In the
      current literature, it was shown that due to a restricted blood flow during the gas
      insufflation, ischemia develops and with the reperfusion of the organ in deflation period,
      oxidative stress and inflammation increases, leading to ischemia/reperfusion-related organ
      and tissue damages.

      In the proposed study, biomarkers for ischemia/reperfusion-inflicted damage will be evaluated
      in a biochemical and histopathological perspective in biopsy samples of ovaries from a young
      patient group in which hysterectomy and bilateral salpingo-oophorectomy will be performed,
      laparoscopically.
In the laparoscopic salpingo-oophorectomy, after the induction of anesthesia, an umbilical
      skin incision was performed. Pneumoperitoneum was established using dry, nonheated CO2
      insufflation through a Veress needle. A 10-mm trocar was inserted into the abdominal cavity
      through the umbilical incision for the laparoscope. Subsequently, three 5-mm ancillary
      trocars, 2 on the lower abdominal quadrants and 1 on the left upper quadrant, were introduced
      to the abdominal space under direct optic visualization. IAP was set at 14 mm Hg and
      maintained with a gas insufflator (Endoflator; Karl Storz Endoscopy, Tuttlingen,
      Germany)Immediately after the port placement, unilateral oophorectomy was performed, and
      ovarian biopsies were obtained. The operation continued with ligation and transection of the
      contralateral utero-ovarian ligament and the bilateral round ligaments. The contralateral
      infundibulopelvic ligament, which contains the main vascular supply for the contralateral
      ovary, remained intact. Subsequently, anterior and posterior leaflets of the broad ligament
      were identified and dissected, and the bladder was placed away from the lower uterine
      segment. The uterus removed from vaginal way after necessary steps. After desufflation, the
      cuff closure procedure was performed vaginally. At the end of the closure, pneumoperitoneum
      was reestablished, the remaining contralateral ovary was removed immediately, and biopsies
      were obtained for histologic analyses.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Impact of CO2 pneumoperitoneum on ovaries by comparing histopathology
time frame: 1-day (at the time of the surgery)
description: Histopathological investigation of ovaries after CO2 pneumoperitoneum -induced I/R
arm group label: Investigation
arm group type: Other
description: Unilateral oophorectomy was performed immediately after abdominal entry, and the remaining contralateral ovary was excised at the end of the hysterectomy in order to compare the effect of these surgical procedures on ovarian tissue.
intervention type: Procedure
intervention name: laparoscopic salpingo-oophorectomy
description: Laparoscopic bilateral salpingo-oophorectomy
arm group label: Investigation
intervention type: Procedure
intervention name: Laparoscopic bilateral salpingo-oophorectomy
description: Unilateral oophorectomy was performed immediately after abdominal entry, and the remaining contralateral ovary was excised at the end of the hysterectomy in order to compare the effect of these surgical procedures on ovarian tissue.
arm group label: Investigation
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Turkey
citation: Guven S, Muci E, Unsal MA, Yulug E, Alver A, Kadioglu Duman M, Mentese A. The effects of carbon dioxide pneumoperitoneum on ovarian blood flow, oxidative stress markers, and morphology during laparoscopy: a rabbit model. Fertil Steril. 2010 Mar 1;93(4):1327-32. doi: 10.1016/j.fertnstert.2008.10.053. Epub 2008 Dec 9.
PMID: 19081089
citation: Schafer M, Krahenbuhl L. Effect of laparoscopy on intra-abdominal blood flow. Surgery. 2001 Apr;129(4):385-9. doi: 10.1067/msy.2001.110224. No abstract available.
PMID: 11283527
citation: Cevrioglu AS, Yilmaz S, Koken T, Tokyol C, Yilmazer M, Fenkci IV. Comparison of the effects of low intra-abdominal pressure and ischaemic preconditioning on the generation of oxidative stress markers and inflammatory cytokines during laparoscopy in rats. Hum Reprod. 2004 Sep;19(9):2144-51. doi: 10.1093/humrep/deh380. Epub 2004 Jun 30.
PMID: 15229201
citation: Biler A, Yucebilgin S, Sendag F, Akman L, Akdemir A, Ates U, Uyanikgil Y, Yilmaz-Dilsiz O, Sezer E. The effects of different intraabdominal pressure protocols in laparoscopic procedures on oxidative stress markers and morphology in rat ovaries. Adv Clin Exp Med. 2014 Nov-Dec;23(6):885-92. doi: 10.17219/acem/37331.
PMID: 25618113
citation: Akdemir A, Taylan E, Sahin C, Ozgurel B, Karlitepe A, Zekioglu O, Ercan G. The Impact of Carbon Dioxide Pneumoperitoneum on Ovarian Ischemia-Reperfusion Injury during Laparoscopic Surgery: A Preliminary Study. J Minim Invasive Gynecol. 2018 May-Jun;25(4):638-643. doi: 10.1016/j.jmig.2017.10.018. Epub 2017 Nov 28.
PMID: 29107119
responsible party type: Sponsor-Investigator
investigator affiliation: Ege University
investigator full name: Ismet Hortu
investigator title: Clinical researcher, Ismet Hortu, MD., PhD. Department of Obstetrics and Gynecology, Ege University School of Medicine, Izmir, Turkey
mesh term: Pneumoperitoneum
mesh term: Reperfusion Injury
mesh term: Ischemia
sharing ipd: Undecided