Approximately 14 million U.S. women have provoked vestibulodynia (PVD), a type of localized vulvar pain which causes major disruption in the everyday lives of up to 60% of affected women and negatively impacts sexual function in 45%. The financial burden imposed on the health care system is also significant, as these women visit multiple clinicians and specialists, and try numerous, unproven treatments. To date, few randomized controlled trials (RCTs) have been conducted to establish evidence based protocols for PVD management. The first immediate goal is to conduct a multicenter RCT of gabapentin treatment for PVD. Gabapentin was selected because of its efficacy in treating other neuropathic pain conditions and the promising, preliminary data on its use in PVD. This is a significant research project because PVD is a highly prevalent, chronic pain condition that is costly to the health care system and that currently has limited management options available to affected women. The second immediate goal is to define psychophysiologic measures of gabapentin response and to define mechanistically-based PVD subtypes, which may be related to abnormalities in central sensitization, muscle hypertonicity, and autonomic dysregulation. Identifying predictors of treatment response in PVD would have clinical applicability to other chronic pain syndromes, and is consistent with NIH's mission to investigate coexisting pain conditions in order to identify common etiological pathways and develop therapeutic targets.
The specific aims are (1): to test the prediction that pain from tampon insertion (primary outcome measure) is lower in PVD patients when treated with gabapentin compared to when treated with placebo. Additional outcome measures include reported intercourse pain and 24-hour pain, and (2) to test the prediction that gabapentin treatment will reduce mechanical allodynia, reduce area and duration of hypersensitivity induced by intradermal capsaicin, reduce vaginal muscle pain to palpation, decrease the number and intensity of somatic tender points, and increase cardiac beat-to-beat variability. This 16-week, randomized, double-blind, placebo-controlled, crossover study will enroll 120 women between 18-50 years of age who report tenderness localized to the vulvar vestibule, pain with tampon insertion, and, when sexually active, insertional dyspareunia. Electronically entered daily diaries will be used to determine if pain is lower in PVD subjects when treated with gabapentin (up to 3600 mg/d) compared to when treated with placebo. The approach is innovative because it focuses on an understudied condition, in a multicenter setting, using a novel outcome measure (the tampon test), and a newly developed web-based recruitment and patient-reporting tool. Data management will include a mechanism-based analysis of drug effectiveness. These study outcomes will ultimately lead to our long-range goal of identifying underlying pathophysiologic mechanisms of PVD in order to create evidence-based differential diagnoses of subtypes of PVD for more effective and cost-effective management options.

Public Health Relevance

The proposed research is relevant to public health because we will determine the efficacy of gabapentin in women with provoked vestibulodynia, a highly prevalent and distressful condition that causes severe pain in the outer vagina, and which consumes large amounts of health care resources and has few treatment options. We will also identify predictors of treatment response that will have clinical applicability to other chronic pain syndromes, and is relevant to NIH's mission to investigate coexisting pain conditions in order to identify common etiological pathways for developing therapeutic targets.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD065740-04
Application #
8627976
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Parrott, Estella C
Project Start
2011-03-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
4
Fiscal Year
2014
Total Cost
$535,667
Indirect Cost
$88,310
Name
University of Tennessee Health Science Center
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Wesselmann, Ursula; Bonham, Adrienne; Foster, David (2014) Vulvodynia: Current state of the biological science. Pain 155:1696-701
Balabathula, Pavan; Bhattacharjee, Himanshu; Thoma, Laura A et al. (2014) Potency and Stability of Intradermal Capsaicin: Implications for Use as a Human Model of Pain in Multicenter Clinical Trials. Clin Exp Pharmacol 4:142
Brown, Candace S; Bachmann, Gloria A; Foster, David C et al. (2013) Challenge of conducting a multicenter clinical trial: experience in commencing a vulvodynia research protocol. J Womens Health (Larchmt) 22:291-2
Brown, Candace S; Foster, David C; Wan, Jim Y et al. (2013) Rationale and design of a multicenter randomized clinical trial of extended release gabapentin in provoked vestibulodynia and biological correlates of response. Contemp Clin Trials 36:154-65