<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/NCT04499131</url>
  </required_header>
  <id_info>
    <org_study_id>1901-VLC-014-EL</org_study_id>
    <nct_id>NCT04499131</nct_id>
  </id_info>
  <brief_title>Impact of Different Doses and Routes of Exogenous Progesterone Administration on Endometrial Receptivity Parameters</brief_title>
  <acronym>PROGENDO</acronym>
  <official_title>Exploratory Study on the Impact of Different Doses and Route of Administration of Exogenous Progesterone in Artificial Endometrial Preparation Cycles on Endometrial Structure and Function</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Valenciano de Infertilidad, IVI VALENCIA</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto Valenciano de Infertilidad, IVI VALENCIA</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>
      After so many years conducting artificial endometrial preparation cycles for embryo transfer,&#xD;
      there is no clear indication about which is the optimal dose of exogenous progesterone in&#xD;
      this scenario to optimize the outcome. Taking into account that the luteal phase can be&#xD;
      controlled by measuring serum P levels (not done until now), the next step is to find out&#xD;
      which is the best dose and route of administration of exogenous progesterone for luteal phase&#xD;
      in artificial cycles.&#xD;
&#xD;
      Therefore, the aim of this experimental study is to compare the endometrial function and&#xD;
      structure, as well as the serum P levels according to the use of different types of exogenous&#xD;
      progesterone available on the market depending on their doses and route of administration&#xD;
      (vaginal, subcutaneous or intramuscular). The endometrial receptivity status will be compared&#xD;
      in the different artificial cycles with the one observed in a natural cycle, without&#xD;
      exogenous progesterone (only the endogenous one) as a control group.&#xD;
&#xD;
      Endometrial receptivity will be analysed by means of endometrial function and structure, but&#xD;
      not by pregnancy outcome as in this study an embryo cannot be replaced in the uterus because&#xD;
      an endometrial biopsy needs to be done to do this type of research.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 9, 2021</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Exploratory, unicentric, with blind evaluators, randomized to six parallel arms in ratio 1:1:1:1:1:1 clinical trial conducted in healthy volunteers under an artificial endometrial preparation cycle and luteal phase support with exogenous progesterone administered by different doses and routes or natural menstrual cycles.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Patients will be evaluated by blinded gynecologist in order to prevent the application of personal criteria and protect the consistence of the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Endometrial gene expression profile</measure>
    <time_frame>12 months</time_frame>
    <description>Determination of gene expression</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Histological dating of endometrial biopsies</measure>
    <time_frame>12 months</time_frame>
    <description>Endometrial classification using Noyes criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histological analysis of the endometrial tissue using electron microscopy</measure>
    <time_frame>12 months</time_frame>
    <description>Presence or Absence of Pinopodes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progesterone concentration in the endometrium</measure>
    <time_frame>12 months</time_frame>
    <description>Endometrial progesterone values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Progesterone concentrations</measure>
    <time_frame>12 months</time_frame>
    <description>Blood serum progesterone values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between progesterone levels in blood and uterus.</measure>
    <time_frame>12 months</time_frame>
    <description>Presence or Absence of correlation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between serum and uterine levels with endometrial transcriptome and histological dating</measure>
    <time_frame>12 months</time_frame>
    <description>Presence or Absence of correlation</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Infertility, Female</condition>
  <condition>ENDOMETRIAL RECEPTIVITY</condition>
  <arm_group>
    <arm_group_label>I: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Artificial endometrial preparation cycle with estrogens and vaginal natural micronized progesterone 400mg/12h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>II: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/24h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>III: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/12h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IV: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Artificial endometrial preparation cycle with estrogens and a combination of subcutaneous natural progesterone 25mg/24h + vaginal natural micronized progesterone 400mg/24h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>V: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Artificial endometrial preparation cycle with estrogens and intramuscular natural progesterone 50mg/24h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Natural menstrual cycle</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Natural menstrual cycle (without any exogenous steroid hormone Treatment)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Progesterone</intervention_name>
    <description>Subjects will undergo an artificial cycle with hormone replacement therapy (HRT) with the aim of comparing the endometrial gene expression profile in the different types of exogenous progesterone with different doses and routes of administration.</description>
    <arm_group_label>I: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_label>II: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_label>III: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_label>IV: Artificial endometrial preparation cycle</arm_group_label>
    <arm_group_label>V: Artificial endometrial preparation cycle</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Artificial Cycle (no intervention)</intervention_name>
    <description>Control group of 15 subjects in the context of a natural cycle with only endogenous progesterone present</description>
    <arm_group_label>Natural menstrual cycle</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        All women with no history of infertility who agree to participate in the study:&#xD;
&#xD;
          1. Age: 18-35 years old, both inclusive&#xD;
&#xD;
          2. Regular menstrual cycles&#xD;
&#xD;
          3. In good health and not suffering from any mental or medical condition(s) that would&#xD;
             preclude participation in the study.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Subjects who meet one or more of the following will not be considered eligible to&#xD;
        participate in the pilot study:&#xD;
&#xD;
          1. Simultaneous participation in other clinical studies that, at the researcher's&#xD;
             criteria, could interfere with the results of this study.&#xD;
&#xD;
          2. Taking oral contraceptives in the three months prior to signing informed consent.&#xD;
&#xD;
          3. Presence of uterine pathology (submucosal or intramural myomas &gt;4 cm deforming cavity,&#xD;
             endometrial polyps or müllerian anomalies) or adnexal pathology (communicating&#xD;
             hydrosalpinx).&#xD;
&#xD;
          4. Background of thrombosis, breast cancer, systemic diseases.&#xD;
&#xD;
          5. Those unable to comprehend the investigational nature of the proposed study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>LAURA CARACENA</last_name>
    <phone>963050999</phone>
    <phone_ext>11054</phone_ext>
    <email>Laura.Caracena@ivirma.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Instituto Valenciano de Infertilidad Spain</name>
      <address>
        <city>Valencia</city>
        <zip>46015</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>ELENA LABARTA, MD</last_name>
      <phone>34 96 3050900</phone>
      <email>elabarta@ivirma.com</email>
    </contact>
    <investigator>
      <last_name>Ernesto Bosch, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elena Labarta, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Pilar Alama, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Josep Lluis Romero, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patricia Diaz-Gimeno, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patricia Sebastian, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Cristina Rodríguez</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>February 20, 2023</last_update_submitted>
  <last_update_submitted_qc>February 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Luteal phase</keyword>
  <keyword>Artificial endometrial preparation cycle</keyword>
  <keyword>Progesterone</keyword>
  <keyword>Endometrial gene expression</keyword>
  <keyword>Endometrial receptivity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infertility</mesh_term>
    <mesh_term>Infertility, Female</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Progesterone</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/NCT04499131
org study id: 1901-VLC-014-EL
nct id: NCT04499131
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
After so many years conducting artificial endometrial preparation cycles for embryo transfer,
      there is no clear indication about which is the optimal dose of exogenous progesterone in
      this scenario to optimize the outcome. Taking into account that the luteal phase can be
      controlled by measuring serum P levels (not done until now), the next step is to find out
      which is the best dose and route of administration of exogenous progesterone for luteal phase
      in artificial cycles.

      Therefore, the aim of this experimental study is to compare the endometrial function and
      structure, as well as the serum P levels according to the use of different types of exogenous
      progesterone available on the market depending on their doses and route of administration
      (vaginal, subcutaneous or intramuscular). The endometrial receptivity status will be compared
      in the different artificial cycles with the one observed in a natural cycle, without
      exogenous progesterone (only the endogenous one) as a control group.

      Endometrial receptivity will be analysed by means of endometrial function and structure, but
      not by pregnancy outcome as in this study an embryo cannot be replaced in the uterus because
      an endometrial biopsy needs to be done to do this type of research.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Exploratory, unicentric, with blind evaluators, randomized to six parallel arms in ratio 1:1:1:1:1:1 clinical trial conducted in healthy volunteers under an artificial endometrial preparation cycle and luteal phase support with exogenous progesterone administered by different doses and routes or natural menstrual cycles.
primary purpose: Treatment
masking: Single (Investigator)
masking description: Patients will be evaluated by blinded gynecologist in order to prevent the application of personal criteria and protect the consistence of the study.
measure: Endometrial gene expression profile
time frame: 12 months
description: Determination of gene expression
measure: Histological dating of endometrial biopsies
time frame: 12 months
description: Endometrial classification using Noyes criteria
measure: Histological analysis of the endometrial tissue using electron microscopy
time frame: 12 months
description: Presence or Absence of Pinopodes
measure: Progesterone concentration in the endometrium
time frame: 12 months
description: Endometrial progesterone values
measure: Serum Progesterone concentrations
time frame: 12 months
description: Blood serum progesterone values
measure: Correlation between progesterone levels in blood and uterus.
time frame: 12 months
description: Presence or Absence of correlation
measure: Correlation between serum and uterine levels with endometrial transcriptome and histological dating
time frame: 12 months
description: Presence or Absence of correlation
arm group label: I: Artificial endometrial preparation cycle
arm group type: Experimental
description: Artificial endometrial preparation cycle with estrogens and vaginal natural micronized progesterone 400mg/12h
arm group label: II: Artificial endometrial preparation cycle
arm group type: Experimental
description: Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/24h
arm group label: III: Artificial endometrial preparation cycle
arm group type: Experimental
description: Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/12h
arm group label: IV: Artificial endometrial preparation cycle
arm group type: Experimental
description: Artificial endometrial preparation cycle with estrogens and a combination of subcutaneous natural progesterone 25mg/24h + vaginal natural micronized progesterone 400mg/24h
arm group label: V: Artificial endometrial preparation cycle
arm group type: Experimental
description: Artificial endometrial preparation cycle with estrogens and intramuscular natural progesterone 50mg/24h
arm group label: Natural menstrual cycle
arm group type: Active Comparator
description: Natural menstrual cycle (without any exogenous steroid hormone Treatment)
intervention type: Drug
intervention name: Progesterone
description: Subjects will undergo an artificial cycle with hormone replacement therapy (HRT) with the aim of comparing the endometrial gene expression profile in the different types of exogenous progesterone with different doses and routes of administration.
arm group label: I: Artificial endometrial preparation cycle
arm group label: II: Artificial endometrial preparation cycle
arm group label: III: Artificial endometrial preparation cycle
arm group label: IV: Artificial endometrial preparation cycle
arm group label: V: Artificial endometrial preparation cycle
intervention type: Other
intervention name: Artificial Cycle (no intervention)
description: Control group of 15 subjects in the context of a natural cycle with only endogenous progesterone present
arm group label: Natural menstrual cycle
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: LAURA CARACENA
phone: 963050999
phone ext: 11054
email: Laura.Caracena@ivirma.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Spain
responsible party type: Sponsor
mesh term: Infertility
mesh term: Infertility, Female
mesh term: Progesterone
sharing ipd: Undecided