A Trial of Gabapentin in Vulvodynia: Biological Correlates of Response

Study Overview
=================
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.

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

Conditions
-----------------
Vulvodynia

Intervention / Treatment
-----------------
* Drug: Placebo oral capsule
* Drug: Gabapentin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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, Greater than 3 continuous months of insertional (entryway) dyspareunia, pain to touch, or both with tampon insertion (modified 'Friedrich's Criteria', and 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: Other vulvar conditions, including dermatoses, vulvitis, vulvar papillomatosis, or atrophic vaginitis (presence of a maturation index) previous vestibulotomy active vaginal infection (positive Affirm ™ VPIII microbial identification test) pregnancy or at risk for pregnancy and not using a reliable birth control method for at least 3 months prior to entering the study 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 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 multiple allergies 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 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) topical lidocaine use 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 Subject who have previously taken gabapentin or Lyrica but discontinued the medication due to side effects are not eligible Subjects with active infections (Candida, BV, trichomonas, chlamydia, GC and HSV via Affirm/culture) must be treated and re-screened to eligible for participation 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 Subjects who have had gastric bypass surgery are ineligible for study participation due to drug absorption problems HPV/abnormal Pap is not exclusionary Ongoing counseling and/or physical therapy is not exclusionary Subjects who report signs of mixed Vulvodynia (spontaneous/provoked, localized, generalized) during prescreening will not be excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo oral capsule<br>Placebo capsule daily in first intervention period and Gabapentin capsule 3000 mg daily in in second intervention (after washout period) | Drug: Placebo oral capsule<br>* Placebo 2 capsules am and 3 capsules pm<br>* Other names: Sugar pill;Drug: Gabapentin<br>* Gabapentin 1200 mg am and 1800 mg pm<br>* Other names: Gralise 600 mg capsule;|
| Active Comparator: Gabapentin<br>Gabapentin capsule 3000 mg daily in first intervention period and Placebo capsule in second intervention (after washout period) | Drug: Placebo oral capsule<br>* Placebo 2 capsules am and 3 capsules pm<br>* Other names: Sugar pill;Drug: Gabapentin<br>* Gabapentin 1200 mg am and 1800 mg pm<br>* Other names: Gralise 600 mg capsule;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tampon Test Pain Intensity | Tampon pain on a 11-point Numeric Rating Scale (0 = no pain at all; 10 = worse pain ever). One tampon was inserted each week. Tampon pain was assessed during last week of maintenance phase (7 days). | Week 6 for each treatment arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coital Pain | Coital pain on an 11-point Numeric Rating Scale (0 = no pain at all; 10 = worse pain ever), assessed after each sexual intercourse event. The number of sexual intercourse events was averaged during final week of each treatment arm. | Week 6 of each treatment arm | 
| Vulvodynia Pain | Overall vulvodynia pain on an 11-point Numeric Rating Scale (0 = no pain at all; 10 = worse pain ever). Pain was assessed daily during the last week of treatment. Daily scores were averaged. | Week 6 for each treatment arm | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vulvodynia