<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/NCT03248076</url>
  </required_header>
  <id_info>
    <org_study_id>Opioids-OPU</org_study_id>
    <nct_id>NCT03248076</nct_id>
  </id_info>
  <brief_title>Effect of Fentanyl on Main Opioid Receptor (OPRM1) on Human Granulosa Cells.</brief_title>
  <official_title>Effect of Fentanyl on Expression of Main Opioid Receptor (OPRM1) on Human Granulosa Cells During Ultrasound-guided Transvaginal Oocyte Retrieval.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>George Papanicolaou Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Papanikolaou Evaggelos</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Naidecki Robert</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Pakaki Fay</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Raikos Nikolaos</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>George Papanicolaou 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>
      Opioids is known that produce not only analgesia but also hyperalgesia through activation of&#xD;
      central glutaminergic system-GABA. At the same time, recently it was found that the main&#xD;
      opioid receptor (OPRM1) is present on human granulosa cells and exogenous opiates and their&#xD;
      antagonists can influence granulosa cell vascular endothelial growth factor (VEGF) production&#xD;
      via OPRM1, causing ovarian hyperstimulation syndrome.&#xD;
&#xD;
      This study aims to investigate if a single exposure to opioids is enough to produce&#xD;
      activation of stress mechanism during oocyte retrieval.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main opioid receptor (OPRM1) is present on human granulosa cells and exogenous opiates&#xD;
      and their antagonists can influence granulosa cell vascular endothelial growth factor (VEGF)&#xD;
      production via OPRM1, causing ovarian hyperstimulation syndrome.&#xD;
&#xD;
      This study aims to investigate if a single exposure to opioids is enough to produce&#xD;
      activation of stress mechanism during ultrasound-guided oocyte retrieval. It will be measured&#xD;
      the level of cortisone before and 15min after iv administration of fentanyl on blood and on&#xD;
      oocyte fluid.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 1, 2017</start_date>
  <completion_date type="Anticipated">October 10, 2018</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2018</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>fentanyl</measure>
    <time_frame>15 minutes</time_frame>
    <description>fentanyl on blood sample and oocyte fluid</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>cortisone</measure>
    <time_frame>15 min</time_frame>
    <description>cortisone on blood sample and oocyte fluid</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Stress Reaction</condition>
  <condition>Opioid Use</condition>
  <arm_group>
    <arm_group_label>Fentanyl citrate</arm_group_label>
    <description>Baseline blood sample and oocyte fluid will be collected under propofol anesthesia. Fifteen minutes after administration of 1γ/kgfentanyl, it will be collected again blood sample and oocyte fluid. Cortisone and fentanyl level will be measured in all samples.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl Citrate</intervention_name>
    <description>1γ/Kg fentanyl</description>
    <arm_group_label>Fentanyl citrate</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy volunteers oocyte donor&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  American Physical Status I-III, BMI&lt;30,&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Heart failure&#xD;
&#xD;
          -  hepatic failure, hepatitis,&#xD;
&#xD;
          -  drug abuse&#xD;
&#xD;
          -  receiving b blockers&#xD;
&#xD;
          -  receiving b agonists (even bronchodilators)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>32 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Irene Asouhidou, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assisting Nature</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Irene Asouhidou, MD, PhD</last_name>
    <phone>00302310999321</phone>
    <email>iasouh@aol.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Evaggelos Papanikolaou, MD, PhD</last_name>
    <phone>00302310424294</phone>
    <email>drvagpapanikolaou@yahoo.gr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Section of Anatomy, Aristotle University of Thessaloniki</name>
      <address>
        <city>Thessaloníki</city>
        <zip>54124</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Irene Asouhidou, MD, PhD</last_name>
      <phone>2310999321</phone>
      <email>iasouh@aol.com</email>
    </contact>
    <contact_backup>
      <last_name>Evaggelos Papanikolaou, MD, PhD</last_name>
      <phone>+302310424294</phone>
      <email>drvagpapanikolaou@yahoo.gr</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <reference>
    <citation>Bottcher B, Seeber B, Leyendecker G, Wildt L. Impact of the opioid system on the reproductive axis. Fertil Steril. 2017 Aug;108(2):207-213. doi: 10.1016/j.fertnstert.2017.06.009. Epub 2017 Jun 29.</citation>
    <PMID>28669481</PMID>
  </reference>
  <reference>
    <citation>Lunger F, Vehmas AP, Furnrohr BG, Sopper S, Wildt L, Seeber B. Opiate receptor blockade on human granulosa cells inhibits VEGF release. Reprod Biomed Online. 2016 Mar;32(3):316-22. doi: 10.1016/j.rbmo.2015.12.006. Epub 2016 Jan 6.</citation>
    <PMID>26803207</PMID>
  </reference>
  <reference>
    <citation>Kouvaras E, Asprodini EK, Asouchidou I, Vasilaki A, Kilindris T, Michaloudis D, Koukoutianou I, Papatheodoropoulos C, Kostopoulos G. Fentanyl treatment reduces GABAergic inhibition in the CA1 area of the hippocampus 24 h after acute exposure to the drug. Neuropharmacology. 2008 Dec;55(7):1172-82. doi: 10.1016/j.neuropharm.2008.07.025. Epub 2008 Jul 26.</citation>
    <PMID>18706433</PMID>
  </reference>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>August 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>December 13, 2017</last_update_submitted>
  <last_update_submitted_qc>December 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>George Papanicolaou Hospital</investigator_affiliation>
    <investigator_full_name>Asouhidou Irene</investigator_full_name>
    <investigator_title>Assisting Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Stress</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
  </intervention_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/NCT03248076
org study id: Opioids-OPU
nct id: NCT03248076
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Opioids is known that produce not only analgesia but also hyperalgesia through activation of
      central glutaminergic system-GABA. At the same time, recently it was found that the main
      opioid receptor (OPRM1) is present on human granulosa cells and exogenous opiates and their
      antagonists can influence granulosa cell vascular endothelial growth factor (VEGF) production
      via OPRM1, causing ovarian hyperstimulation syndrome.

      This study aims to investigate if a single exposure to opioids is enough to produce
      activation of stress mechanism during oocyte retrieval.
The main opioid receptor (OPRM1) is present on human granulosa cells and exogenous opiates
      and their antagonists can influence granulosa cell vascular endothelial growth factor (VEGF)
      production via OPRM1, causing ovarian hyperstimulation syndrome.

      This study aims to investigate if a single exposure to opioids is enough to produce
      activation of stress mechanism during ultrasound-guided oocyte retrieval. It will be measured
      the level of cortisone before and 15min after iv administration of fentanyl on blood and on
      oocyte fluid.
observational model: Case-Only
time perspective: Prospective
measure: fentanyl
time frame: 15 minutes
description: fentanyl on blood sample and oocyte fluid
measure: cortisone
time frame: 15 min
description: cortisone on blood sample and oocyte fluid
arm group label: Fentanyl citrate
description: Baseline blood sample and oocyte fluid will be collected under propofol anesthesia. Fifteen minutes after administration of 1γ/kgfentanyl, it will be collected again blood sample and oocyte fluid. Cortisone and fentanyl level will be measured in all samples.
intervention type: Drug
intervention name: Fentanyl Citrate
description: 1γ/Kg fentanyl
arm group label: Fentanyl citrate
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 32 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Irene Asouhidou, MD, PhD
role: Principal Investigator
affiliation: Assisting Nature
last name: Irene Asouhidou, MD, PhD
phone: 00302310999321
email: iasouh@aol.com
last name: Evaggelos Papanikolaou, MD, PhD
phone: 00302310424294
email: drvagpapanikolaou@yahoo.gr
facility: 
status: Recruiting
contact: 
contact backup: 
country: Greece
citation: Bottcher B, Seeber B, Leyendecker G, Wildt L. Impact of the opioid system on the reproductive axis. Fertil Steril. 2017 Aug;108(2):207-213. doi: 10.1016/j.fertnstert.2017.06.009. Epub 2017 Jun 29.
PMID: 28669481
citation: Lunger F, Vehmas AP, Furnrohr BG, Sopper S, Wildt L, Seeber B. Opiate receptor blockade on human granulosa cells inhibits VEGF release. Reprod Biomed Online. 2016 Mar;32(3):316-22. doi: 10.1016/j.rbmo.2015.12.006. Epub 2016 Jan 6.
PMID: 26803207
citation: Kouvaras E, Asprodini EK, Asouchidou I, Vasilaki A, Kilindris T, Michaloudis D, Koukoutianou I, Papatheodoropoulos C, Kostopoulos G. Fentanyl treatment reduces GABAergic inhibition in the CA1 area of the hippocampus 24 h after acute exposure to the drug. Neuropharmacology. 2008 Dec;55(7):1172-82. doi: 10.1016/j.neuropharm.2008.07.025. Epub 2008 Jul 26.
PMID: 18706433
responsible party type: Principal Investigator
investigator affiliation: George Papanicolaou Hospital
investigator full name: Asouhidou Irene
investigator title: Assisting Professor
mesh term: Fractures, Stress
mesh term: Fentanyl
sharing ipd: Undecided