<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/NCT04493333</url>
  </required_header>
  <id_info>
    <org_study_id>239531</org_study_id>
    <nct_id>NCT04493333</nct_id>
  </id_info>
  <brief_title>Vaginal Dehydroepiandrosterone (DHEA) in Postmenopausal Breast Cancer Survivors on Aromatase Inhibitors</brief_title>
  <official_title>Comparison of Vaginal Dehydroepiandrosterone (DHEA) to Control for Treatment of Vaginal Symptoms in Postmenopausal Breast Cancer Survivors on Aromatase Inhibitors: A Phase II Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arkansas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AMAG Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Arkansas</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research is to gather information on the safety and effectiveness of&#xD;
      Intrarosa®, also known as Dehydroepiandrosterone (DHEA), and prasterone. By doing this study,&#xD;
      the investigators hope to learn if Intrarosa® can improve vaginal discomfort. Participants&#xD;
      will be assigned to one of two groups. One group will use Intrarosa® once a day. The other&#xD;
      group will use Replens™ two times a week.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be a two-armed, randomized Phase II trial. All study subjects will be asked to fill&#xD;
      out a simple 5-question sexual functioning survey. If any concern about sexual functioning is&#xD;
      noted, the subject will also be asked to fill out a more extensive Sexual functioning tool,&#xD;
      to help determine which domain of sexual functioning is the most bothersome.&#xD;
&#xD;
      Subjects who complete the initial screening will be randomly assigned to the Intrarosa® or&#xD;
      Replens™ arm by a 1:1 ratio. Subjects randomized to the Intrarosa® arm will use 6.5 mg daily&#xD;
      for 12 weeks (±1 week). Subjects randomized to the Replens™ arm will use a vaginal applicator&#xD;
      two times per week for 12 weeks.&#xD;
&#xD;
      At baseline and at 12 weeks, subjects will undergo a physical exam including clinical breast&#xD;
      and gynecological exam. During gynecologic exams, the vaginal Potential of Hydrogen (pH) will&#xD;
      be determined and a swab of vaginal epithelium sent for determination of the Vaginal&#xD;
      Maturation Index (VMI) and Maturation Value (MV). These will be used as objective physiologic&#xD;
      markers to determine the improvement in vaginal atrophy. The cytologist's reading specimens&#xD;
      will be blinded.&#xD;
&#xD;
      Additionally, all study subjects will be asked to fill out questionnaires at baseline and&#xD;
      again in 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 7, 2021</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 2</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>Subjects are randomly assigned to the Intrarosa® or Replens™ arm by a 1:1 ratio. Subjects randomized to the Intrarosa® arm will use 6.5 mg daily for 12 weeks (±1 week). Subjects randomized to the Replens™ arm will use a vaginal applicator two times per week for 12 weeks.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The cytologist's reading specimens will be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in vaginal atrophy</measure>
    <time_frame>12 weeks</time_frame>
    <description>Improvement of the vaginal maturation index (VMI) calculated based on the decrease of the percentage of the parabasal cells and the increase of the sum of the percentages of the intermediate and superficial cells</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Vaginal Atrophy</condition>
  <condition>Postmenopausal Symptoms</condition>
  <condition>Breast Cancer Female</condition>
  <condition>Long-term Survivors</condition>
  <arm_group>
    <arm_group_label>Vaginal DHEA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vaginal insert with 6.5 mg vaginal DHEA self-administered once daily at bedtime for 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vaginal Polycarbophil Moisturizer</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Prefilled vaginal applicator with 2.5 g of polycarbophil vaginal moisturizing gel, self-administered two times per week at night for 12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaginal Dehydroepiandrosterone</intervention_name>
    <description>This is a vaginally administered suppository steroid indicated for the treatment of moderate to severe dyspareunia, a frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause.</description>
    <arm_group_label>Vaginal DHEA</arm_group_label>
    <other_name>Intrarosa®</other_name>
    <other_name>Vaginal DHEA</other_name>
    <other_name>Prasterone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Vaginal Polycarbophil Moisturizer</intervention_name>
    <description>This is an FDA cleared, over-the-counter personal lubricant for vaginal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity and supplement the body's natural lubrication. It is non-sterile, water-based, non-irritating, non-greasy, non-staining vaginal gel delivered as a long-lasting moisturizer for vaginal dryness.</description>
    <arm_group_label>Vaginal Polycarbophil Moisturizer</arm_group_label>
    <other_name>Replens™</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postmenopausal patients with a history of breast cancer who have completed primary&#xD;
             treatment with curative intent, who have been on an aromatase inhibitors (AI) for at&#xD;
             least 6 months&#xD;
&#xD;
          -  Stage I-III, hormone receptor positive breast cancer regardless of human epidermal&#xD;
             growth factor receptor 2 (HER2) status&#xD;
&#xD;
          -  Postmenopause defined as 12 months of spontaneous amenorrhea, or 6 months of&#xD;
             spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) levels &gt; 40&#xD;
             mIU/mL (milli-international units per milliliter), or 6 weeks postsurgical bilateral&#xD;
             oophorectomy with or without hysterectomy. FSH level will be documented on all&#xD;
             subjects.&#xD;
&#xD;
          -  Patients reporting any symptoms of vaginal dryness or dyspareunia as assessed by the&#xD;
             Brief Sexual Symptom Checklist for Women (BSSC-W) or the Female Sexual Function Index&#xD;
             (FSFI)&#xD;
&#xD;
          -  No evidence of active malignant breast or gynecologic disease&#xD;
&#xD;
          -  Absence of undiagnosed, persistent or recurring genital bleeding that has not been&#xD;
             evaluated to determine the cause [6]&#xD;
&#xD;
          -  No planned changes in AI during the study period&#xD;
&#xD;
          -  Mammogram (if appropriate, as determined by the treating physician and will be&#xD;
             documented) within 12 months of study entry&#xD;
&#xD;
          -  Patients with documented normal Pap within 12 months of study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of any estrogen or progesterone depot-preparation drug or progestin implant in the&#xD;
             last 6 months before study entry&#xD;
&#xD;
          -  Use of any androgen or anabolic steroids in the last 6 months before study entry&#xD;
&#xD;
          -  Use of any oral or transdermal hormonal products (estrogen, progestin, or DHEA) within&#xD;
             the last 8 weeks prior to study entry; however, a subject can elect to wait for an&#xD;
             8-week washout period before study entry.&#xD;
&#xD;
          -  Use of any vaginal or intrauterine hormonal products in the last 8 weeks; however, a&#xD;
             subject can elect to wait for an 8-week washout before study entry.&#xD;
&#xD;
          -  Use of any natural over the counter estrogenic products in the last 6 months; however,&#xD;
             a subject can elect to wait for a 6-month washout before study entry.&#xD;
&#xD;
          -  Concomitant vulvar and vaginal surgical or laser treatments&#xD;
&#xD;
          -  Vaginal infection or confounding vulvar or active vaginal disease process&#xD;
&#xD;
          -  Prior radiation to the pelvis or history of gynecologic cancer&#xD;
&#xD;
          -  Inability to tolerate a vaginal/speculum exam&#xD;
&#xD;
          -  Undiagnosed, persistent or recurring genital bleeding or other indication of active&#xD;
             pelvic disease process that has not been evaluated [6]&#xD;
&#xD;
          -  Clinically significant uncontrolled depression or severe psychiatric symptoms&#xD;
&#xD;
          -  If subject has an established routine of inert vaginal lubricant use for routine or&#xD;
             occasional relief of vulvar or vaginal symptoms prior to the study period, it may be&#xD;
             continued during the study period along with the study drug.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gloria Richard-Davis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arkansas</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Joseph A Holley</last_name>
    <phone>501-686-8274</phone>
    <email>JAHolley@uams.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Arkansas for Medical Sciences</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matthew Kovak, MS</last_name>
      <phone>501-686-8274</phone>
      <email>mrkovak@uams.edu</email>
    </contact>
    <investigator>
      <last_name>Gloria Richard-Davis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>May 11, 2023</last_update_submitted>
  <last_update_submitted_qc>May 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Postmenopausal</keyword>
  <keyword>Breast Cancer Survivor</keyword>
  <keyword>Vaginal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcium polycarbophil</mesh_term>
    <mesh_term>Psyllium</mesh_term>
    <mesh_term>Dehydroepiandrosterone</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/NCT04493333
org study id: 239531
nct id: NCT04493333
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research is to gather information on the safety and effectiveness of
      Intrarosa®, also known as Dehydroepiandrosterone (DHEA), and prasterone. By doing this study,
      the investigators hope to learn if Intrarosa® can improve vaginal discomfort. Participants
      will be assigned to one of two groups. One group will use Intrarosa® once a day. The other
      group will use Replens™ two times a week.
This will be a two-armed, randomized Phase II trial. All study subjects will be asked to fill
      out a simple 5-question sexual functioning survey. If any concern about sexual functioning is
      noted, the subject will also be asked to fill out a more extensive Sexual functioning tool,
      to help determine which domain of sexual functioning is the most bothersome.

      Subjects who complete the initial screening will be randomly assigned to the Intrarosa® or
      Replens™ arm by a 1:1 ratio. Subjects randomized to the Intrarosa® arm will use 6.5 mg daily
      for 12 weeks (±1 week). Subjects randomized to the Replens™ arm will use a vaginal applicator
      two times per week for 12 weeks.

      At baseline and at 12 weeks, subjects will undergo a physical exam including clinical breast
      and gynecological exam. During gynecologic exams, the vaginal Potential of Hydrogen (pH) will
      be determined and a swab of vaginal epithelium sent for determination of the Vaginal
      Maturation Index (VMI) and Maturation Value (MV). These will be used as objective physiologic
      markers to determine the improvement in vaginal atrophy. The cytologist's reading specimens
      will be blinded.

      Additionally, all study subjects will be asked to fill out questionnaires at baseline and
      again in 12 weeks.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects are randomly assigned to the Intrarosa® or Replens™ arm by a 1:1 ratio. Subjects randomized to the Intrarosa® arm will use 6.5 mg daily for 12 weeks (±1 week). Subjects randomized to the Replens™ arm will use a vaginal applicator two times per week for 12 weeks.
primary purpose: Supportive Care
masking: Single (Outcomes Assessor)
masking description: The cytologist's reading specimens will be blinded.
measure: Change in vaginal atrophy
time frame: 12 weeks
description: Improvement of the vaginal maturation index (VMI) calculated based on the decrease of the percentage of the parabasal cells and the increase of the sum of the percentages of the intermediate and superficial cells
arm group label: Vaginal DHEA
arm group type: Experimental
description: Vaginal insert with 6.5 mg vaginal DHEA self-administered once daily at bedtime for 12 weeks
arm group label: Vaginal Polycarbophil Moisturizer
arm group type: Active Comparator
description: Prefilled vaginal applicator with 2.5 g of polycarbophil vaginal moisturizing gel, self-administered two times per week at night for 12 weeks
intervention type: Drug
intervention name: Vaginal Dehydroepiandrosterone
description: This is a vaginally administered suppository steroid indicated for the treatment of moderate to severe dyspareunia, a frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause.
arm group label: Vaginal DHEA
other name: Intrarosa®
other name: Vaginal DHEA
other name: Prasterone
intervention type: Combination Product
intervention name: Vaginal Polycarbophil Moisturizer
description: This is an FDA cleared, over-the-counter personal lubricant for vaginal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity and supplement the body's natural lubrication. It is non-sterile, water-based, non-irritating, non-greasy, non-staining vaginal gel delivered as a long-lasting moisturizer for vaginal dryness.
arm group label: Vaginal Polycarbophil Moisturizer
other name: Replens™
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Gloria Richard-Davis, MD
role: Principal Investigator
affiliation: University of Arkansas
last name: Joseph A Holley
phone: 501-686-8274
email: JAHolley@uams.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Calcium polycarbophil
mesh term: Psyllium
mesh term: Dehydroepiandrosterone