<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/NCT03039868</url>
  </required_header>
  <id_info>
    <org_study_id>L17-030</org_study_id>
    <nct_id>NCT03039868</nct_id>
  </id_info>
  <brief_title>Use of Pap Smear Derived Cells to Analyze the Expression of SLC6A14 and GPR81 Genes</brief_title>
  <official_title>Use of Pap Smear Derived Cells to Analyze the Expression of SLC6A14 and GPR81 Genes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas Tech University Health Sciences Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Texas Tech University Health Sciences Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      SLC6A14 may serve as a biomarker for cervical dysplasia or cervical cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      SLC6A14 amino acid transporter Previous research has shown that the expression of the amino&#xD;
      acid transporter SLC6A14 is up-regulated in cervical cancer1. Studies on breast, colon and&#xD;
      pancreatic cancer cells have shown that SLC6A14 amino acid transporter serves the role of&#xD;
      supporting amino acid nutrition to these cancer cells2,3,4. It has also been shown that&#xD;
      genetic deletion or pharmacologic blockade of the above transporter will suppress the growth&#xD;
      of the tumor cells both in vitro and in vivo4,5,6.&#xD;
&#xD;
      We are interested in exploring the expression of SLC6A14 transporter in normal cervical&#xD;
      epithelial cells, in cervical dysplasia and cervical cancer; and to see if expression of this&#xD;
      transporter has any correlation to presence/severity of cervical dysplasia/cancer, and also&#xD;
      to see if this may serve as a biomarker to predict or diagnose the presence of cervical&#xD;
      dysplasia and cervical cancer.&#xD;
&#xD;
      GPR81, a G-protein coupled receptor for lactate Human vagina is predominantly colonized by&#xD;
      Lactobacilli, which convert glycogen in the vaginal epithelial cells to lactic acid. Some&#xD;
      species of Lactobacilli also produce hydrogen peroxide. Both lactate and H2O2 help to keep&#xD;
      the vaginal pH low (acidic &lt;4.5) and also help in preventing colonization of the vagina by&#xD;
      pathogenic bacteria. When the levels of Lactobacilli in the vaginal micro environment change&#xD;
      (as with certain vaginal infections, decline in estrogen levels etc), levels of lactate&#xD;
      decline and H2O2 decline-thus predisposing women to vaginal infections.&#xD;
&#xD;
      Vaginal and cervical fluids contain lactate in millimolar concentrations. Recent studies have&#xD;
      identified a G-protein-coupled cell-surface receptor for lactate,-called GPR81. Studies from&#xD;
      Dr. Ganapathy's lab have shown that activation of the receptor GPR81 in B lymphocytes&#xD;
      enhances the production of IgA antibody, which plays a role in defense mechanisms of mucosal&#xD;
      surfaces. IgA antibodies are seen in high levels in the intestinal, colonic, lung mucosa as&#xD;
      well as vaginal epithelial surfaces. These IgA antibodies protect the colonization of mucosal&#xD;
      surfaces by pathogenic bacteria. Thus GPR 81 is an anti-inflammatory molecule. Hence it may&#xD;
      inversely correlate with cervical dysplasia. We propose to investigate if the vaginal and&#xD;
      cervical epithelial cells express this GPR81, whether GPR81 expression correlates to cervical&#xD;
      dysplasia.&#xD;
&#xD;
      If a correlation exists between lactate levels and GPR81 expression, declining Lactobacilli&#xD;
      levels with associated decline in lactate levels, could lead to decreased GPR81 expression on&#xD;
      epithelial cells, and thus decline in IgA antibody secretion. This could be the reason for&#xD;
      vaginal infections with decreased Lactobacilli. If infection with HPV virus occurs, this will&#xD;
      lead to abnormalities in the Pap smear and potential cervical dysplasia in the future.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    results were not as hypothesized&#xD;
  </why_stopped>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">May 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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Expression of SLC6A14 and GPR81 transporter in cervical epithelial cells measured as &quot;delta Ct&quot; to correlate expression levels to cervical dysplasia and cervical cancer</measure>
    <time_frame>Prospective study over a period of 3 years.</time_frame>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">180</enrollment>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>Normal Pap smears</arm_group_label>
    <description>This is the control group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Abnormal Pap smears</arm_group_label>
    <description>This is the case group.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      RNA will be extracted from Pap smear cells for further analysis.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This study will enroll a minimum of 150 and a maximum of 400 subjects. The subjects will&#xD;
        all be women who present to the Texas Tech Obstetrics and Gynecology Clinics for exams and&#xD;
        are having cervical Pap smear collected as part of their exams. The study subjects will be&#xD;
        recruited after informed consent is obtained and they agree to the collection of 1-2&#xD;
        additional cervical Pap smear specimens to be used for the research study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women who present to the TTUHSC Lubbock OBGYN Clinics for exams and are having&#xD;
             cervical Pap smear collected as part of the evaluations.&#xD;
&#xD;
          2. Women who have vaginal discharge will be also included in the study if they are having&#xD;
             cervical Pap smear collected as part of their exam.&#xD;
&#xD;
          3. Age criteria 21yr- 65yrs or more -per ASCCP guidelines for Pap smears.&#xD;
&#xD;
          4. Patients on any medications will also be included- medications have no effect on Pap&#xD;
             smear results.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who have had a hysterectomy.&#xD;
&#xD;
          2. Women having vaginal Pap smears.&#xD;
&#xD;
          3. Women with known HIV.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>January 30, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>November 11, 2019</last_update_submitted>
  <last_update_submitted_qc>November 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</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/NCT03039868
org study id: L17-030
nct id: NCT03039868
lead sponsor: 
has dmc: No
SLC6A14 may serve as a biomarker for cervical dysplasia or cervical cancer.
SLC6A14 amino acid transporter Previous research has shown that the expression of the amino
      acid transporter SLC6A14 is up-regulated in cervical cancer1. Studies on breast, colon and
      pancreatic cancer cells have shown that SLC6A14 amino acid transporter serves the role of
      supporting amino acid nutrition to these cancer cells2,3,4. It has also been shown that
      genetic deletion or pharmacologic blockade of the above transporter will suppress the growth
      of the tumor cells both in vitro and in vivo4,5,6.

      We are interested in exploring the expression of SLC6A14 transporter in normal cervical
      epithelial cells, in cervical dysplasia and cervical cancer; and to see if expression of this
      transporter has any correlation to presence/severity of cervical dysplasia/cancer, and also
      to see if this may serve as a biomarker to predict or diagnose the presence of cervical
      dysplasia and cervical cancer.

      GPR81, a G-protein coupled receptor for lactate Human vagina is predominantly colonized by
      Lactobacilli, which convert glycogen in the vaginal epithelial cells to lactic acid. Some
      species of Lactobacilli also produce hydrogen peroxide. Both lactate and H2O2 help to keep
      the vaginal pH low (acidic <4.5) and also help in preventing colonization of the vagina by
      pathogenic bacteria. When the levels of Lactobacilli in the vaginal micro environment change
      (as with certain vaginal infections, decline in estrogen levels etc), levels of lactate
      decline and H2O2 decline-thus predisposing women to vaginal infections.

      Vaginal and cervical fluids contain lactate in millimolar concentrations. Recent studies have
      identified a G-protein-coupled cell-surface receptor for lactate,-called GPR81. Studies from
      Dr. Ganapathy's lab have shown that activation of the receptor GPR81 in B lymphocytes
      enhances the production of IgA antibody, which plays a role in defense mechanisms of mucosal
      surfaces. IgA antibodies are seen in high levels in the intestinal, colonic, lung mucosa as
      well as vaginal epithelial surfaces. These IgA antibodies protect the colonization of mucosal
      surfaces by pathogenic bacteria. Thus GPR 81 is an anti-inflammatory molecule. Hence it may
      inversely correlate with cervical dysplasia. We propose to investigate if the vaginal and
      cervical epithelial cells express this GPR81, whether GPR81 expression correlates to cervical
      dysplasia.

      If a correlation exists between lactate levels and GPR81 expression, declining Lactobacilli
      levels with associated decline in lactate levels, could lead to decreased GPR81 expression on
      epithelial cells, and thus decline in IgA antibody secretion. This could be the reason for
      vaginal infections with decreased Lactobacilli. If infection with HPV virus occurs, this will
      lead to abnormalities in the Pap smear and potential cervical dysplasia in the future.
observational model: Case-Control
time perspective: Prospective
measure: Expression of SLC6A14 and GPR81 transporter in cervical epithelial cells measured as "delta Ct" to correlate expression levels to cervical dysplasia and cervical cancer
time frame: Prospective study over a period of 3 years.
arm group label: Normal Pap smears
description: This is the control group.
arm group label: Abnormal Pap smears
description: This is the case group.
RNA will be extracted from Pap smear cells for further analysis.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
minimum age: 21 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
sharing ipd: No