<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/NCT04475744</url>
  </required_header>
  <id_info>
    <org_study_id>1912-FIVI-113-SH</org_study_id>
    <nct_id>NCT04475744</nct_id>
  </id_info>
  <brief_title>4-step ASCOT in POI Women to Promote Follicular Rescue</brief_title>
  <official_title>4-step ASCOT in POI Women to Promote Follicular Rescue</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación IVI</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Instituto Valenciano de Infertilidad, IVI VALENCIA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>IVI Madrid</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Universitario La Fe</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundación IVI</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>
      To promote follicular development in POI women, G-CSF mobilized activated platelet rich&#xD;
      plasma will be directly injected into the ovarian medulla.&#xD;
&#xD;
      This is a prospective, observational, multicentric, open, pilot-controlled randomized trial&#xD;
      which seeks to evaluate the impact of the 4-step ASCOT technique on the ovarian reserve and&#xD;
      reproductive outcomes of POI patients. The study will be developed in two phases.&#xD;
&#xD;
      In a first step, POI women will randomized to control or undergo the 4-step ASCOT technique&#xD;
      based on the direct ovarian injection of G-CSF mobilized and activated PRP. Follow up (AFC,&#xD;
      AMH, FSH and E2 determinations) will be developed for 3 month in the controls and for 6&#xD;
      months in the treated and COS initiated if growing antral follicles detected. In the second&#xD;
      phase, POI women allocated to control group after completed the follow up period will undergo&#xD;
      the 4-step ASCOT technique, as described in the previous phase but only one ovary will be&#xD;
      injected, then they will undergo a 6-month follow up period as described above.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 5, 2021</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AFC</measure>
    <time_frame>6-month</time_frame>
    <description>Follicular development assessed by antral follicular count between controls and treated patients after the 4-step ASCOT technique during the follow up period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>FSH, AMH and E2 levels</measure>
    <time_frame>6-month</time_frame>
    <description>hormone levels in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of COS and IVF cycle parameters for each patient, initiated before and after treatment.</measure>
    <time_frame>6-month</time_frame>
    <description>COS and IVF cycle variables will be recorded if COS initiated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Menses recovery (YES/NO)</measure>
    <time_frame>6-12 months</time_frame>
    <description>If menses recovery is noted by patients should be informed and recorded</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ovarian function (YES/NO)</measure>
    <time_frame>6-12 months</time_frame>
    <description>Antral follicles detected by untrasound, menses recover and decrease in FSH levels will be considered as positive ovarian function</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Premature Ovarian Insufficiency</condition>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>POI women radomized to control arm will undergo a 3-month follow up for: AFC, AMH, FSH and E2 determinations.COS will be initiated if growing antral follicles detected. In the second phase, POI women allocated to control group after completed the follow up period will undergo the 4-step ASCOT technique, as described in the previous phase but only one ovary will be injected, then they will undergo a 6-month follow up period as described above.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4-step ASCOT arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>POI women randomized to the 4-step ASCOT technique will receive a direct ovarian injection of G-CSF mobilized and activated PRP. For each patient, both ovaries will be directly injected with the G-CFS activated PRP (4-step ASCOT). Follow up (AFC, AMH, FSH and E2 determinations) will be developed for 6 months and COS initiated if growing antral follicles detected.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>G-CSF treatment for Bone marrow derived stem cell Mobilization</intervention_name>
    <description>Mobilization treatment. On the fifth day, collection will be started.</description>
    <arm_group_label>4-step ASCOT arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Platelet Rich Plasma ovarian injection</intervention_name>
    <description>Mobilized peripheral blood will be obtained to prepare the PRP for injection. Both ovaries will be injected when proper anatomical access can be assessed.</description>
    <arm_group_label>4-step ASCOT arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who meet the following will be considered eligible to participate in the&#xD;
             clinical trial:&#xD;
&#xD;
               1. Informed consent form dated and signed.&#xD;
&#xD;
               2. Age between 18 and 38 (both inclusive)&#xD;
&#xD;
               3. Women who meet the ESHRE criteria for POI [41]&#xD;
&#xD;
                    -  presence of menstrual disturbance defined as oligo/amenorrhea for at least 4&#xD;
                       months&#xD;
&#xD;
                    -  biochemical confirmation as evidenced by an elevated FSH level &gt;25IU/L on&#xD;
                       two occasions &gt; 4 weeks apart&#xD;
&#xD;
                    -  Or fluctuating POI when one of the above criteria is missing.&#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 clinical trial:&#xD;
&#xD;
               1. Simultaneous participation in another clinical study that, at the researcher's&#xD;
                  criteria, could interfere with the results of this study.&#xD;
&#xD;
               2. Age ≥ 39&#xD;
&#xD;
               3. Autoimmune origin of POI&#xD;
&#xD;
               4. Genetic risk factors for POR (e.g. Turner Syndrome, FMR1 premutation, etc);&#xD;
&#xD;
               5. Acquired conditions associated with POR (e.g. Chemotherapy);&#xD;
&#xD;
               6. Clinical endometriosis&#xD;
&#xD;
               7. Previous ovarian surgery considered as a risk of POR&#xD;
&#xD;
               8. Previous gonadotoxic treatment&#xD;
&#xD;
               9. Known intolerance or allergic reactions to components of the study product, i.e.&#xD;
                  lactose&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>38 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>IVI Madrid</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IVI Valencia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>January 24, 2023</last_update_submitted>
  <last_update_submitted_qc>January 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Menopause, Premature</mesh_term>
    <mesh_term>Primary Ovarian Insufficiency</mesh_term>
  </condition_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/NCT04475744
org study id: 1912-FIVI-113-SH
nct id: NCT04475744
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
To promote follicular development in POI women, G-CSF mobilized activated platelet rich
      plasma will be directly injected into the ovarian medulla.

      This is a prospective, observational, multicentric, open, pilot-controlled randomized trial
      which seeks to evaluate the impact of the 4-step ASCOT technique on the ovarian reserve and
      reproductive outcomes of POI patients. The study will be developed in two phases.

      In a first step, POI women will randomized to control or undergo the 4-step ASCOT technique
      based on the direct ovarian injection of G-CSF mobilized and activated PRP. Follow up (AFC,
      AMH, FSH and E2 determinations) will be developed for 3 month in the controls and for 6
      months in the treated and COS initiated if growing antral follicles detected. In the second
      phase, POI women allocated to control group after completed the follow up period will undergo
      the 4-step ASCOT technique, as described in the previous phase but only one ovary will be
      injected, then they will undergo a 6-month follow up period as described above.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AFC
time frame: 6-month
description: Follicular development assessed by antral follicular count between controls and treated patients after the 4-step ASCOT technique during the follow up period.
measure: FSH, AMH and E2 levels
time frame: 6-month
description: hormone levels in plasma
measure: Number of COS and IVF cycle parameters for each patient, initiated before and after treatment.
time frame: 6-month
description: COS and IVF cycle variables will be recorded if COS initiated
measure: Menses recovery (YES/NO)
time frame: 6-12 months
description: If menses recovery is noted by patients should be informed and recorded
measure: Ovarian function (YES/NO)
time frame: 6-12 months
description: Antral follicles detected by untrasound, menses recover and decrease in FSH levels will be considered as positive ovarian function
arm group label: Control arm
arm group type: No Intervention
description: POI women radomized to control arm will undergo a 3-month follow up for: AFC, AMH, FSH and E2 determinations.COS will be initiated if growing antral follicles detected. In the second phase, POI women allocated to control group after completed the follow up period will undergo the 4-step ASCOT technique, as described in the previous phase but only one ovary will be injected, then they will undergo a 6-month follow up period as described above.
arm group label: 4-step ASCOT arm
arm group type: Experimental
description: POI women randomized to the 4-step ASCOT technique will receive a direct ovarian injection of G-CSF mobilized and activated PRP. For each patient, both ovaries will be directly injected with the G-CFS activated PRP (4-step ASCOT). Follow up (AFC, AMH, FSH and E2 determinations) will be developed for 6 months and COS initiated if growing antral follicles detected.
intervention type: Drug
intervention name: G-CSF treatment for Bone marrow derived stem cell Mobilization
description: Mobilization treatment. On the fifth day, collection will be started.
arm group label: 4-step ASCOT arm
intervention type: Procedure
intervention name: Platelet Rich Plasma ovarian injection
description: Mobilized peripheral blood will be obtained to prepare the PRP for injection. Both ovaries will be injected when proper anatomical access can be assessed.
arm group label: 4-step ASCOT arm
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 38 Years
healthy volunteers: No
facility: 
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Menopause, Premature
mesh term: Primary Ovarian Insufficiency