<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/NCT02984774</url>
  </required_header>
  <id_info>
    <org_study_id>53684</org_study_id>
    <nct_id>NCT02984774</nct_id>
  </id_info>
  <brief_title>Assessment of Telomerase Activity in Endometrial Tissue and Serum in Endometriosis Patients</brief_title>
  <official_title>Does Telomerase Activity Have an Effect on Infertility in Patients With Endometriosis ? Assessment of Telomerase Activity in Eutopic, Ectopic Endometrial Tissue and Serum</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Istanbul University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Istanbul University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of the study was the detection of telomerase activity in eutopic, ectopic&#xD;
      endometrial tissue and in peripheral blood and finding the correlation between the telomerase&#xD;
      activity and clinic findings. With these results, confirmation of the hypothesis regarding&#xD;
      the endometriosis pathogenesis and endometriosis-related infertility was aimed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Although distorted pelvic anatomy, impaired peritoneal, humoral and cellular functions,&#xD;
      decreased implantation rate, oocyte and embryo quality, obstructed utero tubal connection are&#xD;
      most researched aspects of endometriosis-related infertility, etiopathogenesis of&#xD;
      endometriosis-related infertility still remains controversial.&#xD;
&#xD;
      Endometrial cell is a unique eukaryotic somatic cell with cyclic telomerase activity.&#xD;
      Hormone-dependent cyclic variation of endometrial telomerase activity was stated in previous&#xD;
      studies. On the other hand telomerase, activity was shown in endometriotic lesions, whereas&#xD;
      this activity lacks in most of the somatic cells.&#xD;
&#xD;
      In this study, assessment of possible relation to increased telomerase activity in infertile&#xD;
      patients with endometriosis was aimed.&#xD;
&#xD;
      Before published studies were assessed telomerase activity in benign and malign gynecological&#xD;
      conditions and in endometriosis tissue, as well. But evaluation of ectopic and eutopic&#xD;
      endometrial tissue and serum telomerase activity in infertile and fertile endometriosis and&#xD;
      healthy control subjects was not performed.&#xD;
&#xD;
      Correlation of telomerase activity and endometriosis-related infertility was aimed in this&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Telomerase activity</measure>
    <time_frame>through study completion, an average of 1 year</time_frame>
    <description>Assessment of telomerase activity with Telomeric Repeat Amplification Protocol Polymerase Chain Reaction method from tissue and blood</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Age in years</measure>
    <time_frame>During admission to hospital for surgery</time_frame>
    <description>From patient anamnesis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Marital status (single, married, divorced, widow)</measure>
    <time_frame>During admission to hospital for surgery</time_frame>
    <description>From patient anamnesis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Smoking status ( yes/no)</measure>
    <time_frame>During admission to hospital for surgery</time_frame>
    <description>From patient anamnesis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI in kg/m2</measure>
    <time_frame>During admission to hospital for surgery</time_frame>
    <description>From patient anamnesis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cystic size in cm</measure>
    <time_frame>During operation</time_frame>
    <description>Macroscopically assessment during surgery</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Endometriosis Ovaries</condition>
  <condition>Infertility, Female</condition>
  <arm_group>
    <arm_group_label>Infertile endometriosis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cystic wall segment from cystectomy material, endometrial sampling during the surgery and peripheric blood sampling during intravenous catheterization during anesthesia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fertile endometriosis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cystic wall segment from cystectomy material, endometrial sampling during the surgery and peripheric blood sampling during intravenous catheterization during anesthesia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Ovarian tissue sampling, endometrial sampling from hysterectomy and oophorectomy pieces and peripheric blood sampling during intravenous catheterization during anesthesia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Cystectomy</intervention_name>
    <description>Segment of cystic wall from the patients for planned cystectomy was taken after operation and was preserved at -80º Celsius for further analysis</description>
    <arm_group_label>Fertile endometriosis</arm_group_label>
    <arm_group_label>Infertile endometriosis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endometrial sampling</intervention_name>
    <description>Endometrial sampling was performed at the same operation with the planned operation for the main indication and was preserved at -80º Celsius for further analysis</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Fertile endometriosis</arm_group_label>
    <arm_group_label>Infertile endometriosis</arm_group_label>
    <other_name>Pipelle endometrial suction curettage</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheric blood sampling</intervention_name>
    <description>4 cc peripheric venous blood was sampled into the EDTA(Ethylenediaminetetraacetic acid)-containing tubes during catheterization for anesthesia was preserved at 4º Celsius for further analysis</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Fertile endometriosis</arm_group_label>
    <arm_group_label>Infertile endometriosis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Ovarian tissue sampling</intervention_name>
    <description>2cm linear tissue sample from ovarian cortex was performed at the same operation with the planned operation for the main indication and was preserved at -80º Celsius for further analysis</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Clinical diagnosis of Infertility Clinical and histological diagnosis of endometriosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Malign disorders Hormone replacement treatment Oral Contraceptive using&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Engin Oral, MD</last_name>
    <role>Study Director</role>
    <affiliation>Istanbul University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nigar Sofiyeva</name>
      <address>
        <city>Istanbul</city>
        <state>Non-US/Non-Canadian</state>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <reference>
    <citation>Schenken RS, Asch RH, Williams RF, Hodgen GD. Etiology of infertility in monkeys with endometriosis: luteinized unruptured follicles, luteal phase defects, pelvic adhesions, and spontaneous abortions. Fertil Steril. 1984 Jan;41(1):122-30. doi: 10.1016/s0015-0282(16)47552-7.</citation>
    <PMID>6420199</PMID>
  </reference>
  <reference>
    <citation>Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, Agarwal A. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002 Feb;17(2):426-31. doi: 10.1093/humrep/17.2.426.</citation>
    <PMID>11821289</PMID>
  </reference>
  <reference>
    <citation>Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002;54(2):82-7. doi: 10.1159/000067717.</citation>
    <PMID>12566749</PMID>
  </reference>
  <reference>
    <citation>Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001 Jan;75(1):1-10. doi: 10.1016/s0015-0282(00)01630-7.</citation>
    <PMID>11163805</PMID>
  </reference>
  <reference>
    <citation>Genbacev OD, Prakobphol A, Foulk RA, Krtolica AR, Ilic D, Singer MS, Yang ZQ, Kiessling LL, Rosen SD, Fisher SJ. Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science. 2003 Jan 17;299(5605):405-8. doi: 10.1126/science.1079546.</citation>
    <PMID>12532021</PMID>
  </reference>
  <reference>
    <citation>Cunha-Filho JS, Gross JL, Bastos de Souza CA, Lemos NA, Giugliani C, Freitas F, Passos EP. Physiopathological aspects of corpus luteum defect in infertile patients with mild/minimal endometriosis. J Assist Reprod Genet. 2003 Mar;20(3):117-21. doi: 10.1023/a:1022625106489.</citation>
    <PMID>12735387</PMID>
  </reference>
  <reference>
    <citation>Kissler S, Hamscho N, Zangos S, Gatje R, Muller A, Rody A, Dobert N, Menzel C, Grunwald F, Siebzehnrubl E, Kaufmann M. Diminished pregnancy rates in endometriosis due to impaired uterotubal transport assessed by hysterosalpingoscintigraphy. BJOG. 2005 Oct;112(10):1391-6. doi: 10.1111/j.1471-0528.2005.00676.x.</citation>
    <PMID>16167942</PMID>
  </reference>
  <reference>
    <citation>Tanaka M, Kyo S, Takakura M, Kanaya T, Sagawa T, Yamashita K, Okada Y, Hiyama E, Inoue M. Expression of telomerase activity in human endometrium is localized to epithelial glandular cells and regulated in a menstrual phase-dependent manner correlated with cell proliferation. Am J Pathol. 1998 Dec;153(6):1985-91. doi: 10.1016/S0002-9440(10)65712-4.</citation>
    <PMID>9846988</PMID>
  </reference>
  <reference>
    <citation>Williams CD, Boggess JF, LaMarque LR, Meyer WR, Murray MJ, Fritz MA, Lessey BA. A prospective, randomized study of endometrial telomerase during the menstrual cycle. J Clin Endocrinol Metab. 2001 Aug;86(8):3912-7. doi: 10.1210/jcem.86.8.7729.</citation>
    <PMID>11502832</PMID>
  </reference>
  <results_reference>
    <citation>Kim CM, Oh YJ, Cho SH, Chung DJ, Hwang JY, Park KH, Cho DJ, Choi YM, Lee BS. Increased telomerase activity and human telomerase reverse transcriptase mRNA expression in the endometrium of patients with endometriosis. Hum Reprod. 2007 Mar;22(3):843-9. doi: 10.1093/humrep/del425. Epub 2006 Oct 31.</citation>
    <PMID>17077107</PMID>
  </results_reference>
  <results_reference>
    <citation>Hapangama DK, Turner MA, Drury JA, Quenby S, Saretzki G, Martin-Ruiz C, Von Zglinicki T. Endometriosis is associated with aberrant endometrial expression of telomerase and increased telomere length. Hum Reprod. 2008 Jul;23(7):1511-9. doi: 10.1093/humrep/den172. Epub 2008 May 2.</citation>
    <PMID>18456668</PMID>
  </results_reference>
  <results_reference>
    <citation>Lehner R, Enomoto T, McGregor JA, Shroyer AL, Haugen BR, Pugazhenthi U, Shroyer KR. Quantitative analysis of telomerase hTERT mRNA and telomerase activity in endometrioid adenocarcinoma and in normal endometrium. Gynecol Oncol. 2002 Jan;84(1):120-5. doi: 10.1006/gyno.2001.6474.</citation>
    <PMID>11748987</PMID>
  </results_reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 3, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <last_update_submitted>December 3, 2016</last_update_submitted>
  <last_update_submitted_qc>December 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 7, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Istanbul University</investigator_affiliation>
    <investigator_full_name>Nigar Sofiyeva</investigator_full_name>
    <investigator_title>Resident Doctor</investigator_title>
  </responsible_party>
  <keyword>Endometriosis</keyword>
  <keyword>Infertility</keyword>
  <keyword>Telomerase activity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Endometriosis</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>General results is available for sharing.</ipd_description>
  </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/NCT02984774
org study id: 53684
nct id: NCT02984774
lead sponsor: 
has dmc: No
The goal of the study was the detection of telomerase activity in eutopic, ectopic
      endometrial tissue and in peripheral blood and finding the correlation between the telomerase
      activity and clinic findings. With these results, confirmation of the hypothesis regarding
      the endometriosis pathogenesis and endometriosis-related infertility was aimed.
Although distorted pelvic anatomy, impaired peritoneal, humoral and cellular functions,
      decreased implantation rate, oocyte and embryo quality, obstructed utero tubal connection are
      most researched aspects of endometriosis-related infertility, etiopathogenesis of
      endometriosis-related infertility still remains controversial.

      Endometrial cell is a unique eukaryotic somatic cell with cyclic telomerase activity.
      Hormone-dependent cyclic variation of endometrial telomerase activity was stated in previous
      studies. On the other hand telomerase, activity was shown in endometriotic lesions, whereas
      this activity lacks in most of the somatic cells.

      In this study, assessment of possible relation to increased telomerase activity in infertile
      patients with endometriosis was aimed.

      Before published studies were assessed telomerase activity in benign and malign gynecological
      conditions and in endometriosis tissue, as well. But evaluation of ectopic and eutopic
      endometrial tissue and serum telomerase activity in infertile and fertile endometriosis and
      healthy control subjects was not performed.

      Correlation of telomerase activity and endometriosis-related infertility was aimed in this
      study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Telomerase activity
time frame: through study completion, an average of 1 year
description: Assessment of telomerase activity with Telomeric Repeat Amplification Protocol Polymerase Chain Reaction method from tissue and blood
measure: Age in years
time frame: During admission to hospital for surgery
description: From patient anamnesis
measure: Marital status (single, married, divorced, widow)
time frame: During admission to hospital for surgery
description: From patient anamnesis
measure: Smoking status ( yes/no)
time frame: During admission to hospital for surgery
description: From patient anamnesis
measure: BMI in kg/m2
time frame: During admission to hospital for surgery
description: From patient anamnesis
measure: Cystic size in cm
time frame: During operation
description: Macroscopically assessment during surgery
arm group label: Infertile endometriosis
arm group type: Experimental
description: Cystic wall segment from cystectomy material, endometrial sampling during the surgery and peripheric blood sampling during intravenous catheterization during anesthesia.
arm group label: Fertile endometriosis
arm group type: Experimental
description: Cystic wall segment from cystectomy material, endometrial sampling during the surgery and peripheric blood sampling during intravenous catheterization during anesthesia.
arm group label: Control
arm group type: Other
description: Ovarian tissue sampling, endometrial sampling from hysterectomy and oophorectomy pieces and peripheric blood sampling during intravenous catheterization during anesthesia.
intervention type: Procedure
intervention name: Cystectomy
description: Segment of cystic wall from the patients for planned cystectomy was taken after operation and was preserved at -80º Celsius for further analysis
arm group label: Fertile endometriosis
arm group label: Infertile endometriosis
intervention type: Procedure
intervention name: Endometrial sampling
description: Endometrial sampling was performed at the same operation with the planned operation for the main indication and was preserved at -80º Celsius for further analysis
arm group label: Control
arm group label: Fertile endometriosis
arm group label: Infertile endometriosis
other name: Pipelle endometrial suction curettage
intervention type: Procedure
intervention name: Peripheric blood sampling
description: 4 cc peripheric venous blood was sampled into the EDTA(Ethylenediaminetetraacetic acid)-containing tubes during catheterization for anesthesia was preserved at 4º Celsius for further analysis
arm group label: Control
arm group label: Fertile endometriosis
arm group label: Infertile endometriosis
intervention type: Procedure
intervention name: Ovarian tissue sampling
description: 2cm linear tissue sample from ovarian cortex was performed at the same operation with the planned operation for the main indication and was preserved at -80º Celsius for further analysis
arm group label: Control
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Engin Oral, MD
role: Study Director
affiliation: Istanbul University
facility: 
country: Turkey
citation: Schenken RS, Asch RH, Williams RF, Hodgen GD. Etiology of infertility in monkeys with endometriosis: luteinized unruptured follicles, luteal phase defects, pelvic adhesions, and spontaneous abortions. Fertil Steril. 1984 Jan;41(1):122-30. doi: 10.1016/s0015-0282(16)47552-7.
PMID: 6420199
citation: Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, Agarwal A. Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod. 2002 Feb;17(2):426-31. doi: 10.1093/humrep/17.2.426.
PMID: 11821289
citation: Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest. 2002;54(2):82-7. doi: 10.1159/000067717.
PMID: 12566749
citation: Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001 Jan;75(1):1-10. doi: 10.1016/s0015-0282(00)01630-7.
PMID: 11163805
citation: Genbacev OD, Prakobphol A, Foulk RA, Krtolica AR, Ilic D, Singer MS, Yang ZQ, Kiessling LL, Rosen SD, Fisher SJ. Trophoblast L-selectin-mediated adhesion at the maternal-fetal interface. Science. 2003 Jan 17;299(5605):405-8. doi: 10.1126/science.1079546.
PMID: 12532021
citation: Cunha-Filho JS, Gross JL, Bastos de Souza CA, Lemos NA, Giugliani C, Freitas F, Passos EP. Physiopathological aspects of corpus luteum defect in infertile patients with mild/minimal endometriosis. J Assist Reprod Genet. 2003 Mar;20(3):117-21. doi: 10.1023/a:1022625106489.
PMID: 12735387
citation: Kissler S, Hamscho N, Zangos S, Gatje R, Muller A, Rody A, Dobert N, Menzel C, Grunwald F, Siebzehnrubl E, Kaufmann M. Diminished pregnancy rates in endometriosis due to impaired uterotubal transport assessed by hysterosalpingoscintigraphy. BJOG. 2005 Oct;112(10):1391-6. doi: 10.1111/j.1471-0528.2005.00676.x.
PMID: 16167942
citation: Tanaka M, Kyo S, Takakura M, Kanaya T, Sagawa T, Yamashita K, Okada Y, Hiyama E, Inoue M. Expression of telomerase activity in human endometrium is localized to epithelial glandular cells and regulated in a menstrual phase-dependent manner correlated with cell proliferation. Am J Pathol. 1998 Dec;153(6):1985-91. doi: 10.1016/S0002-9440(10)65712-4.
PMID: 9846988
citation: Williams CD, Boggess JF, LaMarque LR, Meyer WR, Murray MJ, Fritz MA, Lessey BA. A prospective, randomized study of endometrial telomerase during the menstrual cycle. J Clin Endocrinol Metab. 2001 Aug;86(8):3912-7. doi: 10.1210/jcem.86.8.7729.
PMID: 11502832
citation: Kim CM, Oh YJ, Cho SH, Chung DJ, Hwang JY, Park KH, Cho DJ, Choi YM, Lee BS. Increased telomerase activity and human telomerase reverse transcriptase mRNA expression in the endometrium of patients with endometriosis. Hum Reprod. 2007 Mar;22(3):843-9. doi: 10.1093/humrep/del425. Epub 2006 Oct 31.
PMID: 17077107
citation: Hapangama DK, Turner MA, Drury JA, Quenby S, Saretzki G, Martin-Ruiz C, Von Zglinicki T. Endometriosis is associated with aberrant endometrial expression of telomerase and increased telomere length. Hum Reprod. 2008 Jul;23(7):1511-9. doi: 10.1093/humrep/den172. Epub 2008 May 2.
PMID: 18456668
citation: Lehner R, Enomoto T, McGregor JA, Shroyer AL, Haugen BR, Pugazhenthi U, Shroyer KR. Quantitative analysis of telomerase hTERT mRNA and telomerase activity in endometrioid adenocarcinoma and in normal endometrium. Gynecol Oncol. 2002 Jan;84(1):120-5. doi: 10.1006/gyno.2001.6474.
PMID: 11748987
responsible party type: Principal Investigator
investigator affiliation: Istanbul University
investigator full name: Nigar Sofiyeva
investigator title: Resident Doctor
mesh term: Infertility
mesh term: Endometriosis
mesh term: Infertility, Female
sharing ipd: Undecided
ipd description: General results is available for sharing.