<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/NCT03301480</url>
  </required_header>
  <id_info>
    <org_study_id>PRO17050002</org_study_id>
    <nct_id>NCT03301480</nct_id>
  </id_info>
  <brief_title>Contraceptive/HIV Affecting Risk in Adolescents</brief_title>
  <acronym>CHARA</acronym>
  <official_title>Contraceptive/HIV Affecting Risk in Adolescents</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</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>
      This study will evaluate the impact of hormonal contraceptives on HIV risk associated with&#xD;
      changes to the innate immunity in the female genital tract in a cross-sectional study. HIV&#xD;
      risk will be evaluated by the capacity of cervical tissue to replicate HIV when challenged ex&#xD;
      vivo and correlated to the number of CD4 T cells, DCs, and macrophages; the capacity of&#xD;
      cervicovaginal fluid to inhibit HIV will be correlated to soluble mucosal mediators, and the&#xD;
      vaginal microbiota. The lower genital tract samples will be collected from 120 adolescents&#xD;
      aged 18-19 (40 using no hormonal contraception, 40 using ENG-I, 40 using LNG-IUS). For&#xD;
      comparison, 90 adult women aged 25-45 will be equally distributed between the same groupings.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    An interim review of the data revealed that there was broad inter-participant variability.The&#xD;
    study was stopped due to futility.&#xD;
  </why_stopped>
  <start_date type="Actual">July 31, 2017</start_date>
  <completion_date type="Actual">September 17, 2018</completion_date>
  <primary_completion_date type="Actual">September 17, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>HIV replication in cervical tissue as measured by levels of HIV p24/viral transcripts</measure>
    <time_frame>baseline</time_frame>
    <description>cervical tissue testing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>number of immune cells in cervical tissue, including CD45, CD3, CD4, and CD8 and their expression of CCR5, CCR6 and CD69, and CD11c+ DCs and CD14+ macrophages</measure>
    <time_frame>baseline</time_frame>
    <description>cervical tissue testing</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Prevalence of bacterial vaginosis defined as a Nugent score ≥7 on a vaginal smear</measure>
    <time_frame>baseline</time_frame>
    <description>vaginal specimen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>prevalence and quantity of lactobacillus species and bacterial vaginosis associated bacteria as measured by traditional culture methods and quantitative PCR</measure>
    <time_frame>baseline</time_frame>
    <description>vaginal specimen</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV inhibitory activity in mucosal fluid; and soluble mucosal factors identified through pathway analyses and confirmed by targeted ELISA/multiplexing technology (proteases/ anti-proteases, keratin, IFNε, and other molecules)</measure>
    <time_frame>baseline</time_frame>
    <description>mucosal fluid</description>
  </secondary_outcome>
  <number_of_groups>6</number_of_groups>
  <enrollment type="Actual">120</enrollment>
  <condition>Contraception</condition>
  <condition>Hiv</condition>
  <arm_group>
    <arm_group_label>No contraception/18-19 years old</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Use of ENG-I/18 - 19 years old</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>LNG-IUS/18-19 years old</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>No Contraception/ 25 - 45 years old</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Use of ENG-I/25 - 45 years old</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>LNG-IUS/25-45 years old</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        non-pregnant, HIV negative, healthy 18-19 year old women and 25-45 year old women&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Meets one of the following age groups (at the time of sample collection):&#xD;
&#xD;
               1. Adolescent aged 18-19&#xD;
&#xD;
               2. Adult aged 25-45&#xD;
&#xD;
          2. Meets one of the following contraception groups:&#xD;
&#xD;
               1. Regular menstrual cycles by participant history (if not using hormonal&#xD;
                  contraception)&#xD;
&#xD;
               2. Use of ENG-I (i.e. Implanon/Nexplanon) for at least 30 days by participant&#xD;
                  history&#xD;
&#xD;
               3. Use of LNG-IUS (Mirena or Skyla) for at least 30 days by participant history&#xD;
&#xD;
          3. HIV uninfected Note: HIV testing will be done as part of screening. However, if a&#xD;
             woman participated in a recent research study and has an HIV test result available&#xD;
             from that study, this will suffice provided the date of the test is within 6 months of&#xD;
             the study visit.&#xD;
&#xD;
          4. Willing to undergo pelvic exam and collection of cervical biopsies&#xD;
&#xD;
          5. Willing to provided written informed consent&#xD;
&#xD;
          6. Agree to be sexually abstinent for 48 hours prior to the cervical biopsies and for one&#xD;
             week after the biopsies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Use of any other hormonal contraception other than ENG-I or LNG-IUS&#xD;
&#xD;
          2. Use of a diaphragm or spermicide for contraception&#xD;
&#xD;
          3. Pregnant or pregnancy within 90 days&#xD;
&#xD;
          4. Currently breastfeeding&#xD;
&#xD;
          5. Currently menstruating/bleeding (at time of specimen collection) Note: participant can&#xD;
             return after cessation of bleeding for specimen collection&#xD;
&#xD;
          6. Past participation in more than one study involving cervical biopsies per participant&#xD;
             report&#xD;
&#xD;
          7. Cervical biopsies within one month of specimen collection visit&#xD;
&#xD;
          8. Abnormal vaginal discharge or other genital tract symptoms at the time of specimen&#xD;
             collection&#xD;
&#xD;
          9. Pelvic findings on the day of specimen collection consistent with cervicitis (i.e.&#xD;
             MPC, erythema, edema) or anatomy making cervical biopsies difficult&#xD;
&#xD;
         10. Menopausal&#xD;
&#xD;
         11. Hysterectomy&#xD;
&#xD;
         12. History of malignancy of the genital tract (including cervix, uterus, vagina, and&#xD;
             vulva)&#xD;
&#xD;
         13. History of immunosuppression (including HIV infection, diabetes, and chronic steroid&#xD;
             use)&#xD;
&#xD;
         14. Known history of a platelet/bleeding/clotting disorder&#xD;
&#xD;
         15. Use of a systemic or vaginal antimicrobial agent within 7 days of specimen collection&#xD;
&#xD;
         16. Use of any vaginal product (i.e. douching, spermicide, lubricant) or device within 7&#xD;
             days of specimen collection Note: tampon use is acceptable&#xD;
&#xD;
         17. Any other condition that in the opinion of the Study Investigator would preclude&#xD;
             provision of informed consent or make study participation unsafe, complicate the&#xD;
             interpretation of study outcome data, or otherwise interfere with achieving the study&#xD;
             objectives.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>participants must have a cervix for participation</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Katherine Bunge, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Magee-Womens Hospital of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>September 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>February 5, 2019</last_update_submitted>
  <last_update_submitted_qc>February 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Katherine Bunge</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <!-- 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/NCT03301480
org study id: PRO17050002
nct id: NCT03301480
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will evaluate the impact of hormonal contraceptives on HIV risk associated with
      changes to the innate immunity in the female genital tract in a cross-sectional study. HIV
      risk will be evaluated by the capacity of cervical tissue to replicate HIV when challenged ex
      vivo and correlated to the number of CD4 T cells, DCs, and macrophages; the capacity of
      cervicovaginal fluid to inhibit HIV will be correlated to soluble mucosal mediators, and the
      vaginal microbiota. The lower genital tract samples will be collected from 120 adolescents
      aged 18-19 (40 using no hormonal contraception, 40 using ENG-I, 40 using LNG-IUS). For
      comparison, 90 adult women aged 25-45 will be equally distributed between the same groupings.
observational model: Case-Control
time perspective: Cross-Sectional
measure: HIV replication in cervical tissue as measured by levels of HIV p24/viral transcripts
time frame: baseline
description: cervical tissue testing
measure: number of immune cells in cervical tissue, including CD45, CD3, CD4, and CD8 and their expression of CCR5, CCR6 and CD69, and CD11c+ DCs and CD14+ macrophages
time frame: baseline
description: cervical tissue testing
measure: Prevalence of bacterial vaginosis defined as a Nugent score ≥7 on a vaginal smear
time frame: baseline
description: vaginal specimen
measure: prevalence and quantity of lactobacillus species and bacterial vaginosis associated bacteria as measured by traditional culture methods and quantitative PCR
time frame: baseline
description: vaginal specimen
measure: HIV inhibitory activity in mucosal fluid; and soluble mucosal factors identified through pathway analyses and confirmed by targeted ELISA/multiplexing technology (proteases/ anti-proteases, keratin, IFNε, and other molecules)
time frame: baseline
description: mucosal fluid
arm group label: No contraception/18-19 years old
arm group label: Use of ENG-I/18 - 19 years old
arm group label: LNG-IUS/18-19 years old
arm group label: No Contraception/ 25 - 45 years old
arm group label: Use of ENG-I/25 - 45 years old
arm group label: LNG-IUS/25-45 years old
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: participants must have a cervix for participation
minimum age: 18 Years
maximum age: 45 Years
last name: Katherine Bunge, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Katherine Bunge
investigator title: Assistant Professor