Vulvodynia: Identification of Potential Relevant Biomarkers

Activation of the Sphingosine-1-phosphate (S1P) to S1P1 Receptor Subtype (S1PR1) Axis in Patients With Vulvodynia: Identification of Potential Relevant Biomarkers

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.

Study Overview

• Status: Completed
• Conditions: Vulvodynia

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63107
      • St. Lukes Doctors South Office building
    • Saint Louis, Missouri, United States, 63117
      • 1031 Bellevue office suite 200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

For patients with vulvodynia-related painwill be offered enrollment into the study. At their visit before treatment begins they will have:

blood drawn ,(about 10ml-two teaspoons) this is research related. The ISSVD (The International Society for the Study of Vulvovaginal Disease) classification and diagnostic criteria for vulvodynia will be used for inclusion in this study.

Vulvodynia - Vulvar pain of at least 3 months' duration,

Descriptors:

• Localized (e.g. vestibulodynia, clitorodynia) or Generalized or Mixed (localized and generalized)
• Provoked (e.g. insertional, contact) or Spontaneous or Mixed (provoked and spontaneous)
• Onset (primary or secondary)
• Temporal pattern (intermittent, persistent, constant, immediate, delayed)

Description

Inclusion Criteria:

• 18-70 years of age
• Vulvar pain of at least 3 months' duration
• Localized (e.g. vestibulodynia, clitorodynia) or Generalized or Mixed
• Provoked or Spontaneous or Mixed Onset
• Temporal pattern

Exclusion Criteria:

• <18 or >70 years of age
• pregnant
• Not able to provide consent
• Patients with active vulvar dystrophies.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
S1PR1 elevation	S1PR1 is elevated in the peripheral blood leukocytes (PBLs) of patients with vulvodyna-related pain.	up to one year

Collaborators and Investigators

• Sponsor: St. Louis University
• Investigators: Principal Investigator: Cherie LeFevre, MD, St. Louis University

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2019
• Primary Completion (Actual): June 10, 2020
• Study Completion (Actual): June 10, 2020

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: December 1, 2016
• First Posted (Estimate): December 5, 2016

Study Record Updates

• Last Update Posted (Actual): August 27, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vulvar Diseases; Vulvodynia
• Other Study ID Numbers: 27036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No