Clinical trial NCT01301001: A Trial of Gabapentin in Vulvodynia: Biological Correlates of Response
Official title: A Controlled Trial of Gabapentin in Vulvodynia: Biological Correlates of Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vulvodynia
Keywords: Vulvodynia
Lead sponsor: University of Tennessee
Sponsor class: OTHER
First posted: 2011-02-23
Enrollment: 230
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This is a 18-week, randomized, double-blind, placebo-controlled, two-treatment, two-period crossover design, where 120 women between 18 of age and older 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.

Eligibility criteria: Inclusion Criteria:

1. Women who are 18 years of age and older, as long as no vaginal atrophy is present. If vaginal atrophy is present, then topical hormone replacement can be provided for a minimum of 6 weeks and then she must be re-screened to be eligible,
2. Greater than 3 continuous months of insertional (entryway) dyspareunia, pain to touch, or both with tampon insertion (modified 'Friedrich's Criteria', 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). 4.) Must report pain with the "Tampon Insertion Pain" Test at visit 1

Exclusion Criteria:

1. Other vulvar conditions, including dermatoses, vulvitis, vulvar papillomatosis, or atrophic vaginitis (presence of a maturation index)
2. previous vestibulotomy
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 \[ABS \< 1.50 x 10-3 μl, \<20%\]), (thrombocytopenia \[platelets \< 100,000 μl\], 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 \> 12 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 benzodiazepines, opiates, muscle relaxants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs) or CNS stimulants (including methylphenidate, amphetamine dextroamphetamine) 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 interstitial cystitis, 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% or greater 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

Primary outcomes:
measure: Tampon Test Pain Intensity
timeFrame: Week 6 for each treatment arm
Secondary outcomes:
measure: Coital Pain
timeFrame: Week 6 of each treatment arm
measure: Vulvodynia Pain
timeFrame: Week 6 for each treatment arm
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Rutgers - Robert Wood Johnson Medical School
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester School of Medicine and Dentistry
state: New York
city: Memphis
country: United States
facility: Clinical Research Center
state: Tennessee
Study officials:
affiliation: University of Tennessee
name: Candace S Brown, MSN, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Rochester
name: David C Foster, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Rutgers Robert Wood Johnson Medical School
name: Gloria A Bachmann, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brown CS, Bachmann GA, Wan J, Foster DC; Gabapentin (GABA) Study Group. Gabapentin for the Treatment of Vulvodynia: A Randomized Controlled Trial. Obstet Gynecol. 2018 Jun;131(6):1000-1007. doi: 10.1097/AOG.0000000000002617.