A Trial of Gabapentin in Vulvodynia: Biological Correlates of Response

Condition(s) targeted: Vulvodynia

Intervention: Gabapentin (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: University of Tennessee

Official(s) and/or principal investigator(s):
Candace S Brown, MSN, PharmD, Principal Investigator, Affiliation: University of Tennessee Health Science Center
David C Foster, M.D., Principal Investigator, Affiliation: University of Rochester School of Medicine and Dentistry
Gloria A Bachmann, M.D., Principal Investigator, Affiliation: University of Medicine and Dentistry New Jersey

Overall contact:
Leslie Rawlinson, Phone: 901-448-6693, Email: lrawlins@uthsc.edu

The Specific aims of this project are to (1) 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. Secondary outcome measures include intercourse pain and 24-hour pain and (2)perform a mechanism-based analysis of gabapentin effectiveness, and to gain insight into the underlying pathophysiology of subtypes of PVD that may lead to more specific treatment options.

Official title: A Controlled Trial of Gabapentin in Vulvodynia: Biological Correlates of Response

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: The primary outcome measure of this project are to test the prediction that pain from tampon insertion is lower in PVD patients when treated with gabapentin compared to when treated with placebo.

Secondary outcome: The secondary outcome measure is to perform a mechanism-based analysis of gabapentin effectiveness, and to gain insight into the underlying pathophysiology of subtypes of PVD that may lead to more specific treatment options.

Detailed description: This is a 16-week, randomized, double-blind, placebo-controlled, two-treatment, two-period crossover design, where 120 women between 18-50 years of age who report insertional dyspareunia, pain with tampon insertion, and tenderness localized to the vulvar vestibule will be enrolled in the study. 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. Biological measurements will include assessment of allodynia and hyperalgesia from capsaicin administration, muscle tension using a vaginal pressure algometer, number of tender points by clinical examination, and changes in blood pressure, pulse and heart rate variability. . The Long-range goals of this project are to explicate the underlying pathophysiologic mechanisms of PVD, and to use this knowledge to create evidence-based differential diagnoses of subtypes of PVD and to individualize treatments for each subtype. The immediate goal is to conduct a multicenter, randomized controlled trial (RCT) of gabapentin treatment for PVD, and which will also provide critical data on a new PVD-testing and response paradigm, as well as on characteristics that may define subtypes of PVD. Gabapentin, an anticonvulsant with analgesic, anxiolytic, and antispasmotic effects, was selected because of its efficacy in treating other neuropathic pain conditions.

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

1. women between 18-50 years of age,

2. 'Friedrich's Criteria' must be met (report greater than six continuous months of vulvar symptoms including insertional dyspareunia, pain with tampon insertion, or pain to touch, demonstrate on physical exam moderate to severe tenderness to light touch, localized to the vulvar vestibule [positive Cotton Swab Test, CST, Section k, Procedures], and demonstration of variable degrees of erythema of the vestibule), and

3. an average pain level of "4" or greater on the 11-point tampon test (0 = no pain at all; 10 = worse pain ever) during the 2-week screening period must be exhibited.

(One tampon will be inserted each week).

Exclusion Criteria:

1. Other vulvar conditions, including dermatoses, vulvitis, vulvar papillomatosis, or atrophic vaginitis (presence of a maturation index)

2. previous vestibulectomy

3. active vaginal infection (positive Affirm ™ VPIII microbial identification test)

4. pregnancy or at risk for pregnancy and not using a reliable birth control method for at least 3 months prior to entering the study

5. any unstable medical condition, including renal impairment (creatinine clearance of ≤60 mL/min, BUN > 30mg/dL, serum creatinine > 2 mg/dL), significant hematological disease (leukopenia [WBC < 3. 0 x 10-3µl, leukocytosis [WBC >20. 0 x 10-3μl], neutropenia [ABS < 1. 50 x 10-3 μl, <20%]), (thrombocytopia [platelets < 100,000 μl], anemia [HCT < 27%, Hbg <8 g/dL, RBC <3 x 10-6]), cardiovascular disease (cardiac conduction disturbance, CHF, hypertension [140/90]), hepatic insufficiency (serum AST, ALT, or ALP ≥ 3 times upper limit of normal), neurological disorder (seizures, syncopal episodes, peripheral neuropathy, severe pain other than that caused by vulvodynia), autoimmune disease, or respiratory illness

6. psychiatric disorder, including history of major depressive disorder or substance abuse disorder within the past 6 months, a score of > 8 on the depression subscale of the Hospital Anxiety and Depression Scale (HADS), indicting a major depressive episode (35,36), a serious risk of suicide, or lifetime history of psychosis, hypomania or mania

7. multiple allergies

8. use of centrally-acting agents, including benzodiazepines, opiates, muscle relaxants, and antidepressants(including SSRIs, SNRIs, and TCAs) within 2 weeks of randomization and during the study

9. use of certain herbal agents within 2 weeks of randomization and during the study, including ginkgo biloba, evening primrose, St. John's Wort, valerian, kava kava)

10. topical lidocaine use

11. Subjects, who are diagnosed with coexisting vaginismus, fibromyalgia and/or intercystitis, must have greater vulvar pain than their coexisting conditions or they will not be eligible for study participation

12. Subject who have previously taken gabapentin or Lyrica but discontinued the medication due to side effects are not eligible

13. Subjects with active infections (Candida, BV, trichomonas, chlamydia, GC and HSV via Affirm/culture) must be treated and re-screened to eligible for participation

14. Subjects with > 10% Parabasal cells and/or vaginal atrophy can be provided with topical hormone replacement for a minimum of 6 weeks and then must be re-screened to be eligible

15. Subjects who have had gastric bypass surgery are ineligible for study participation due to drug absorption problems

16. HPV/abnormal Pap is not exclusionary

17. Ongoing counseling and/or physical therapy is not exclusionary

18. Subjects who report signs of mixed Vulvodynia (spontaneous/provoked, localized, generalized) during prescreening will not be excluded

Leslie Rawlinson, Phone: 901-448-6693, Email: lrawlins@uthsc.edu

UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-1962, United States; Recruiting
Gloria A Bachmann, M.D., Phone: 732-235-7628, Email: bachmaga@umdnj.edu
Gloria A Bachmann, M.D., Principal Investigator

University of Rochester School of Medicine and Dentistry, Rochester, New York 14642-0002, United States; Recruiting
David C Foster, M.D., Phone: 585-273-3232, Email: David_Foster@URMC.Rochester.edu
David C Foster, M.D., Principal Investigator

Clinical Research Center, Memphis, Tennessee 38104, United States; Recruiting
Candace S Brown, MSN, PharmD, Phone: 901-448-6044, Email: csbrown@uthsc.edu
Leslie A Rawlinson, Phone: 901-448-6693, Email: lrawlins@uthsc.edu
Candace S Brown, MSN, PharmD, Principal Investigator

Web link for study information and Pre-screening questionnaire

Starting date: August 2012
Last updated: August 19, 2012