<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/NCT03770026</url>
  </required_header>
  <id_info>
    <org_study_id>181210</org_study_id>
    <nct_id>NCT03770026</nct_id>
  </id_info>
  <brief_title>Autologous Platelet-rich Plasma for Clomiphene Citrate-induced Thin Endometrium</brief_title>
  <official_title>Intrauterine Infusion of Autologous Platelet-rich Plasma to Prevent a Thin Endometrium in Infertile Women Undergoing Clomiphene Citrate Therapy: a Pilot Prospective Self-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Benha University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Benha 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>
      This is a prospective self-controlled clinical study. Women with clomiphene Citrate failure&#xD;
      with thin endometrium less than 7 millimeters for at least 3 cycles will be selected (N =&#xD;
      30). Patients will receive 2 ovarian stimulation cycles with Clomiphene citrate (CC) 100 mg/&#xD;
      day for 5 days from cycle day 3. A control cycle (CC only cycle) woman will continue on CC&#xD;
      alone plus cervical irrigation of cervix with 1 ml of 0.9% normal saline at cycle day 8 and&#xD;
      10 to assure patient-blinded method. The study group, the same will be done plus the&#xD;
      intrauterine infusion of Autologous platelet-rich plasma (PRP) in 8th and 10th days of the&#xD;
      cycle. In both groups, the endometrial thickness and Power Doppler evaluation of their&#xD;
      endometrial and sub-endometrial blood flow will be measured on the day of Human Chorionic&#xD;
      Gonadotropin (HCG) administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pilot prospective self-controlled clinical trial. Women with Clomiphene Citrate&#xD;
      failure with documented thin endometrium less than 7 millimeters for at least 3 stimulation&#xD;
      cycles will be chosen (N = 30). Patients will experience 2 ovarian stimulation cycles with&#xD;
      Clomiphene citrate (CC) in a dose of 100 mg/ day for 5 days starting from cycle day 3. A&#xD;
      control cycle (CC only cycle) woman will continue on Clomiphene Citrate alone plus cervical&#xD;
      irrigation of cervix with 1 ml of 0.9% normal saline at cycle day 8 and 10 to confirm&#xD;
      patient-blinded process.&#xD;
&#xD;
      The study group, the same will be done in addition to the intrauterine infusion of with&#xD;
      Autologous platelet-rich plasma (PRP) in 8th and 10th days of the cycle.&#xD;
&#xD;
      In both groups, the endometrial thickness and Power Doppler evaluation of their endometrial&#xD;
      and sub-endometrial blood flow will be measured on the day of HCG administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">January 1, 2020</completion_date>
  <primary_completion_date type="Actual">January 1, 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endometrial thickness</measure>
    <time_frame>1 day</time_frame>
    <description>Transvaginal sonographic estimation of maximal distance traversing endometrial- myometrial interphase on each endometrial stripe in a -midsagittal plane in the uterine fundus.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Power Doppler estimation of endometrial and sub-endometrial vascularity</measure>
    <time_frame>1 day</time_frame>
    <description>Endometrial and sub-endometrial vascularity signals will be evaluated using the power Doppler.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy rate</measure>
    <time_frame>At the end of a 28-day menstrual cycle.</time_frame>
    <description>Recognizing pregnancy through positive urinary HCG test plus sonographic detection of cardiac pulsations</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Infertility, Female, Associated With Anovulation</condition>
  <arm_group>
    <arm_group_label>Clomiphene citrate only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Infertile women (30 women) with prior clomiphene citrate failure (ovulation was documented without conception), with thin endometrium (&lt;7mm) in at least 3 cycles. Saline cervical flushing will be done at cycle day 8 and 10 to convince patient-blinded procedure.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Platelet-rich plasma plus Clomiphene</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Women who did not conceive on the Clomiphene citrate-only cycle will receive Clomiphene citrate 100 mg/ day starting from the third day of the cycle. Intrauterine Autologous platelet-rich plasma will be done on the cycle days 8 and 10.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>clomiphene citrate</intervention_name>
    <description>Clomiphene citrate-only arm: Patients will receive Clomiphene citrate induction (in a dose of 100 mg/day starting from day 3 of the cycle for 5 days). Sonographic assessment of endometrial thickness together with Power Doppler evaluation endometrial and sub-endometrial blood flow a will be done in the Day of HCG injection.</description>
    <arm_group_label>Clomiphene citrate only</arm_group_label>
    <arm_group_label>Platelet-rich plasma plus Clomiphene</arm_group_label>
    <other_name>Clomiphene</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline cervical flushing</intervention_name>
    <description>Cervical irrigation with 1 ml of 0.9% normal saline will be done at cycle day 8 and 10 to convince patient-blinded procedure.</description>
    <arm_group_label>Clomiphene citrate only</arm_group_label>
    <other_name>Saline</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Intrauterine Autologous platelet-rich plasma</intervention_name>
    <description>Under complete aseptic cares and ultrasound supervision, Autologous platelet-rich plasma (0.5 - 1 ml) was immediately injected into the uterine cavity using an intrauterine insemination catheter in the cycle days 8 and 10. The Autologous platelet-rich plasma is prepared in collaboration with the Department of Clinical Pathology, Faculty of Medicine, Benha University.</description>
    <arm_group_label>Platelet-rich plasma plus Clomiphene</arm_group_label>
    <other_name>Platelet-rich plasma</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women with clomiphene citrate failure (defined as at least previous 3 ovulatory cycles&#xD;
             with clomiphene citrate, with no pregnancy),&#xD;
&#xD;
          -  persistently thin endometrium (less than 7 millimeters in at least 3 cycles).&#xD;
&#xD;
          -  normal baseline Follicle Stimulating Hormone, Luteinizing Hormone, and free&#xD;
             testosterone levels, patent tubes by hysterosalpingography, and satisfactory male&#xD;
             semen analysis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous ovarian surgery;&#xD;
&#xD;
          -  endocrine disorders ;&#xD;
&#xD;
          -  pelvic pathologies;&#xD;
&#xD;
          -  chronic hepatic, cardiovascular, or renal disease;&#xD;
&#xD;
          -  other factors of infertility and&#xD;
&#xD;
          -  use of gonadotropins or hormonal contraception through the latest 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ahmed Walid A Morad</last_name>
    <role>Principal Investigator</role>
    <affiliation>Banha Faculty of Medicine, Banha Univerisity</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banha Faculty Hospital</name>
      <address>
        <city>Banha</city>
        <state>Alkalubia</state>
        <zip>13511</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>April 28, 2020</last_update_submitted>
  <last_update_submitted_qc>April 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Benha University</investigator_affiliation>
    <investigator_full_name>Ahmed Walid Anwar Murad</investigator_full_name>
    <investigator_title>Professor of Obestetrics and Gynecology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
    <mesh_term>Anovulation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clomiphene</mesh_term>
    <mesh_term>Enclomiphene</mesh_term>
    <mesh_term>Zuclomiphene</mesh_term>
  </intervention_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/NCT03770026
org study id: 181210
nct id: NCT03770026
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This is a prospective self-controlled clinical study. Women with clomiphene Citrate failure
      with thin endometrium less than 7 millimeters for at least 3 cycles will be selected (N =
      30). Patients will receive 2 ovarian stimulation cycles with Clomiphene citrate (CC) 100 mg/
      day for 5 days from cycle day 3. A control cycle (CC only cycle) woman will continue on CC
      alone plus cervical irrigation of cervix with 1 ml of 0.9% normal saline at cycle day 8 and
      10 to assure patient-blinded method. The study group, the same will be done plus the
      intrauterine infusion of Autologous platelet-rich plasma (PRP) in 8th and 10th days of the
      cycle. In both groups, the endometrial thickness and Power Doppler evaluation of their
      endometrial and sub-endometrial blood flow will be measured on the day of Human Chorionic
      Gonadotropin (HCG) administration.
This is a pilot prospective self-controlled clinical trial. Women with Clomiphene Citrate
      failure with documented thin endometrium less than 7 millimeters for at least 3 stimulation
      cycles will be chosen (N = 30). Patients will experience 2 ovarian stimulation cycles with
      Clomiphene citrate (CC) in a dose of 100 mg/ day for 5 days starting from cycle day 3. A
      control cycle (CC only cycle) woman will continue on Clomiphene Citrate alone plus cervical
      irrigation of cervix with 1 ml of 0.9% normal saline at cycle day 8 and 10 to confirm
      patient-blinded process.

      The study group, the same will be done in addition to the intrauterine infusion of with
      Autologous platelet-rich plasma (PRP) in 8th and 10th days of the cycle.

      In both groups, the endometrial thickness and Power Doppler evaluation of their endometrial
      and sub-endometrial blood flow will be measured on the day of HCG administration.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Endometrial thickness
time frame: 1 day
description: Transvaginal sonographic estimation of maximal distance traversing endometrial- myometrial interphase on each endometrial stripe in a -midsagittal plane in the uterine fundus.
measure: Power Doppler estimation of endometrial and sub-endometrial vascularity
time frame: 1 day
description: Endometrial and sub-endometrial vascularity signals will be evaluated using the power Doppler.
measure: Clinical pregnancy rate
time frame: At the end of a 28-day menstrual cycle.
description: Recognizing pregnancy through positive urinary HCG test plus sonographic detection of cardiac pulsations
arm group label: Clomiphene citrate only
arm group type: Active Comparator
description: Infertile women (30 women) with prior clomiphene citrate failure (ovulation was documented without conception), with thin endometrium (<7mm) in at least 3 cycles. Saline cervical flushing will be done at cycle day 8 and 10 to convince patient-blinded procedure.
arm group label: Platelet-rich plasma plus Clomiphene
arm group type: Experimental
description: Women who did not conceive on the Clomiphene citrate-only cycle will receive Clomiphene citrate 100 mg/ day starting from the third day of the cycle. Intrauterine Autologous platelet-rich plasma will be done on the cycle days 8 and 10.
intervention type: Drug
intervention name: clomiphene citrate
description: Clomiphene citrate-only arm: Patients will receive Clomiphene citrate induction (in a dose of 100 mg/day starting from day 3 of the cycle for 5 days). Sonographic assessment of endometrial thickness together with Power Doppler evaluation endometrial and sub-endometrial blood flow a will be done in the Day of HCG injection.
arm group label: Clomiphene citrate only
arm group label: Platelet-rich plasma plus Clomiphene
other name: Clomiphene
intervention type: Drug
intervention name: Saline cervical flushing
description: Cervical irrigation with 1 ml of 0.9% normal saline will be done at cycle day 8 and 10 to convince patient-blinded procedure.
arm group label: Clomiphene citrate only
other name: Saline
intervention type: Biological
intervention name: Intrauterine Autologous platelet-rich plasma
description: Under complete aseptic cares and ultrasound supervision, Autologous platelet-rich plasma (0.5 - 1 ml) was immediately injected into the uterine cavity using an intrauterine insemination catheter in the cycle days 8 and 10. The Autologous platelet-rich plasma is prepared in collaboration with the Department of Clinical Pathology, Faculty of Medicine, Benha University.
arm group label: Platelet-rich plasma plus Clomiphene
other name: Platelet-rich plasma
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: No
last name: Ahmed Walid A Morad
role: Principal Investigator
affiliation: Banha Faculty of Medicine, Banha Univerisity
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Benha University
investigator full name: Ahmed Walid Anwar Murad
investigator title: Professor of Obestetrics and Gynecology
mesh term: Infertility
mesh term: Infertility, Female
mesh term: Anovulation
mesh term: Clomiphene
mesh term: Enclomiphene
mesh term: Zuclomiphene