<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/NCT02981433</url>
  </required_header>
  <id_info>
    <org_study_id>27036</org_study_id>
    <nct_id>NCT02981433</nct_id>
  </id_info>
  <brief_title>Vulvodynia: Identification of Potential Relevant Biomarkers</brief_title>
  <official_title>Activation of the Sphingosine-1-phosphate (S1P) to S1P1 Receptor Subtype (S1PR1) Axis in Patients With Vulvodynia: Identification of Potential Relevant Biomarkers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Louis University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Louis University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vulvodynia is a syndrome of unexplained vulvar pain that is frequently accompanied by&#xD;
      physical disabilities, limitation of daily activities (such as sitting and walking), sexual&#xD;
      dysfunction and psychologic disability. Originally suggested by McKay, the term &quot;vulvodynia&quot;&#xD;
      has also been suggested by the International Society for the Study of Vulvar Disease Task&#xD;
      Force to describe any vulvar pain. The incidence and prevalence of vulvodynia have not been&#xD;
      well studied. Age distribution for the condition may range from the 20s to the 60s, and it is&#xD;
      limited almost exclusively to white women. Obstetric and gynecologic history is usually&#xD;
      unremarkable. Risk-taking sexual behavior is rare, and few patients have a history of&#xD;
      sexually transmitted diseases. Vulvar pain usually has an acute onset, at times associated&#xD;
      with episodes of vaginitis or certain therapeutic procedures of the vulva (cryotherapy or&#xD;
      laser therapy). In most cases, vulvodynia becomes a chronic problem lasting months to years.&#xD;
      Vulvar pain is frequently described as burning or stinging, or a feeling of rawness or&#xD;
      irritation.&#xD;
&#xD;
      Most patients consult several physicians before being diagnosed. Many are treated with&#xD;
      multiple topical or systemic medications, with minimal relief. In some cases, inappropriate&#xD;
      therapy may even make the symptoms worse. Since physical findings are few and cultures and&#xD;
      biopsies are frequently negative, patients may be told that the problem is primarily&#xD;
      psychologic, thus invalidating their pain and adding to their distress.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sphingosine-1-phosphate (S1P) is a potent anti-apoptotic sphingolipid with potent&#xD;
      pro-inflammatory actions which are driven in most part by activation of the S1P receptor&#xD;
      subtype S1PR158. Biologically active S1P is generated by the phosphorylation of sphingosine,&#xD;
      catalyzed by two sphingosine kinases (SphK1, SphK2). S1P levels are further regulated by its&#xD;
      dephosphorylation by two phosphatases (SGPP1 and SGPP2) and through degradation by one lyase&#xD;
      (SGPL1). Once released S1P initiates signaling through a family of five cognate G&#xD;
      protein-coupled receptors (S1PR1-5), leading to various cellular responses9. S1P signaling&#xD;
      has important roles in inflammation and cancer. S1P acting via the S1PR1 has been implicated&#xD;
      in the development of pain of several etiologies as discovered by Salvemini and coworkers and&#xD;
      subsequently extended by others. FTY720 (fingolimod/Gilenya®) is the first orally available&#xD;
      agent approved by the FDA for the treatment of relapsing-remitting multiple sclerosis (MS).&#xD;
      The work by Salvemini's group in providing a mechanistic basis for understanding chronic pain&#xD;
      through the S1P/S1PR1 axis, provides a promising therapeutic target for the use of agents&#xD;
      like FTY720 as a novel treatment for pain. Ongoing work by the Salvemini's lab suggests that&#xD;
      increased expression of S1PR1 in circulating peripheral blood leukocytes (PBLs) may provide a&#xD;
      relevant biomarker to predict severity and pain induction outcomes as well as predict patient&#xD;
      responses to anti-S1PR1 approaches.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 13, 2019</start_date>
  <completion_date type="Actual">June 10, 2020</completion_date>
  <primary_completion_date type="Actual">June 10, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>S1PR1 elevation</measure>
    <time_frame>up to one year</time_frame>
    <description>S1PR1 is elevated in the peripheral blood leukocytes (PBLs) of patients with vulvodyna-related pain.</description>
  </primary_outcome>
  <enrollment type="Actual">2</enrollment>
  <condition>Vulvodynia</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Peripheral blood leukocytes (PBLs) may provide a relevant biomarker to predict severity and&#xD;
      pain induction outcomes as well as predict patient responses to anti-S1PR1 approaches.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        For patients with vulvodynia-related painwill be offered enrollment into the study. At&#xD;
        their visit before treatment begins they will have:&#xD;
&#xD;
        blood drawn ,(about 10ml-two teaspoons) this is research related. The ISSVD (The&#xD;
        International Society for the Study of Vulvovaginal Disease) classification and diagnostic&#xD;
        criteria for vulvodynia will be used for inclusion in this study.&#xD;
&#xD;
        Vulvodynia - Vulvar pain of at least 3 months' duration,&#xD;
&#xD;
        Descriptors:&#xD;
&#xD;
          -  Localized (e.g. vestibulodynia, clitorodynia) or Generalized or Mixed (localized and&#xD;
             generalized)&#xD;
&#xD;
          -  Provoked (e.g. insertional, contact) or Spontaneous or Mixed (provoked and&#xD;
             spontaneous)&#xD;
&#xD;
          -  Onset (primary or secondary)&#xD;
&#xD;
          -  Temporal pattern (intermittent, persistent, constant, immediate, delayed)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-70 years of age&#xD;
&#xD;
          -  Vulvar pain of at least 3 months' duration&#xD;
&#xD;
          -  Localized (e.g. vestibulodynia, clitorodynia) or Generalized or Mixed&#xD;
&#xD;
          -  Provoked or Spontaneous or Mixed Onset&#xD;
&#xD;
          -  Temporal pattern&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &lt;18 or &gt;70 years of age&#xD;
&#xD;
          -  pregnant&#xD;
&#xD;
          -  Not able to provide consent&#xD;
&#xD;
          -  Patients with active vulvar dystrophies.&#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>Cherie LeFevre, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Louis University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Lukes Doctors South Office building</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1031 Bellevue office suite 200</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>August 26, 2020</last_update_submitted>
  <last_update_submitted_qc>August 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Louis University</investigator_affiliation>
    <investigator_full_name>Cherie LeFevre, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vulvodynia</mesh_term>
  </condition_browse>
  <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/NCT02981433
org study id: 27036
nct id: NCT02981433
lead sponsor: 
has dmc: No
Vulvodynia is a syndrome of unexplained vulvar pain that is frequently accompanied by
      physical disabilities, limitation of daily activities (such as sitting and walking), sexual
      dysfunction and psychologic disability. Originally suggested by McKay, the term "vulvodynia"
      has also been suggested by the International Society for the Study of Vulvar Disease Task
      Force to describe any vulvar pain. The incidence and prevalence of vulvodynia have not been
      well studied. Age distribution for the condition may range from the 20s to the 60s, and it is
      limited almost exclusively to white women. Obstetric and gynecologic history is usually
      unremarkable. Risk-taking sexual behavior is rare, and few patients have a history of
      sexually transmitted diseases. Vulvar pain usually has an acute onset, at times associated
      with episodes of vaginitis or certain therapeutic procedures of the vulva (cryotherapy or
      laser therapy). In most cases, vulvodynia becomes a chronic problem lasting months to years.
      Vulvar pain is frequently described as burning or stinging, or a feeling of rawness or
      irritation.

      Most patients consult several physicians before being diagnosed. Many are treated with
      multiple topical or systemic medications, with minimal relief. In some cases, inappropriate
      therapy may even make the symptoms worse. Since physical findings are few and cultures and
      biopsies are frequently negative, patients may be told that the problem is primarily
      psychologic, thus invalidating their pain and adding to their distress.
Sphingosine-1-phosphate (S1P) is a potent anti-apoptotic sphingolipid with potent
      pro-inflammatory actions which are driven in most part by activation of the S1P receptor
      subtype S1PR158. Biologically active S1P is generated by the phosphorylation of sphingosine,
      catalyzed by two sphingosine kinases (SphK1, SphK2). S1P levels are further regulated by its
      dephosphorylation by two phosphatases (SGPP1 and SGPP2) and through degradation by one lyase
      (SGPL1). Once released S1P initiates signaling through a family of five cognate G
      protein-coupled receptors (S1PR1-5), leading to various cellular responses9. S1P signaling
      has important roles in inflammation and cancer. S1P acting via the S1PR1 has been implicated
      in the development of pain of several etiologies as discovered by Salvemini and coworkers and
      subsequently extended by others. FTY720 (fingolimod/Gilenya®) is the first orally available
      agent approved by the FDA for the treatment of relapsing-remitting multiple sclerosis (MS).
      The work by Salvemini's group in providing a mechanistic basis for understanding chronic pain
      through the S1P/S1PR1 axis, provides a promising therapeutic target for the use of agents
      like FTY720 as a novel treatment for pain. Ongoing work by the Salvemini's lab suggests that
      increased expression of S1PR1 in circulating peripheral blood leukocytes (PBLs) may provide a
      relevant biomarker to predict severity and pain induction outcomes as well as predict patient
      responses to anti-S1PR1 approaches.
observational model: Case-Only
time perspective: Prospective
measure: S1PR1 elevation
time frame: up to one year
description: S1PR1 is elevated in the peripheral blood leukocytes (PBLs) of patients with vulvodyna-related pain.
Peripheral blood leukocytes (PBLs) may provide a relevant biomarker to predict severity and
      pain induction outcomes as well as predict patient responses to anti-S1PR1 approaches.
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Cherie LeFevre, MD
role: Principal Investigator
affiliation: St. Louis University
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: St. Louis University
investigator full name: Cherie LeFevre, MD
investigator title: Principal Investigator
mesh term: Vulvodynia
sharing ipd: No