A Trial of Gabapentin in Vulvodynia: Biological Correlates of Response | RxWiki

A Trial of Gabapentin in Vulvodynia: Biological Correlates of Response

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Vulvodynia
Intervention	Drug: Gabapentin extended-release
Phase	N/A
Sponsor	University of Tennessee
Responsible Party	University of Tennessee
ClinicalTrials.gov Identifier	NCT01301001
First Received	May 13, 2010
Last Updated	December 16, 2013
Last verified	December 2013

Tracking Information[ + expand ][ + ]

First Received Date	May 13, 2010
Last Updated Date	December 16, 2013
Start Date	August 2012
Estimated Primary Completion Date	March 2015
Current Primary Outcome Measures	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. [Time Frame: 4 years] [Designated as safety issue: No]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.
Current Secondary Outcome Measures	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. [Time Frame: 4 years] [Designated as safety issue: No]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.

Descriptive Information[ + expand ][ + ]

Brief Title	A Trial of Gabapentin in Vulvodynia: Biological Correlates of Response
Official Title	A Controlled Trial of Gabapentin in Vulvodynia: Biological Correlates of Response
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.
Study Type	Interventional
Study Phase	N/A
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Condition	Vulvodynia
Intervention	Drug: Gabapentin extended-release No. of tablets taken daily will increase over a 4 weeks in a step-up manner to a maximum total dose of 3000 mg/d, even if efficacy is achieved at a lower dose, or until the subject develops intolerable adverse effects. The titration schedule is as follows: Week 0: 600 mg pm; Week 1: 600 mg am/600 mg pm; Week 2: 600 mg am/1200 mg pm; Week 3: 600 mg am/1800 mg pm; Week 4: 1200 mg am/1800 mg pm. If side effects are intolerable or do not diminish within 3-4 days, the morning dose will be decreased by one level (600 mg), and an increase will be attempted one more time. If this next increase again results in intolerable side effects, the study drug will be decreased to the level of the previous dose (defined as the maximal tolerated dose) and continued for the remainder of the study (a minimal dose of 1200 mg/d will be permitted). Other Names: Gralise
Study Arm (s)	Active Comparator: gabapentin extended-release This is a 18-week, randomized, double-blind, placebo-controlled, two-treatment, two-period crossover design. A parallel group design was considered but excluded because a crossover design provides the ability to compare several treatment regimens in the same subject and allows for comparison at the individual rather than group level. During the first four weeks of each 8-week treatment period, the dose will be escalated toward a maximal tolerated dose or the target ceiling dose of 3600 mg/d, whichever is reached first. Placebo Comparator: Placebo (sugar pill) This is a 18-week, randomized, double-blind, placebo-controlled, two-treatment, two-period crossover design. A parallel group design was considered but excluded because a crossover design provides the ability to compare several treatment regimens in the same subject and allows for comparison at the individual rather than group level. During the first four weeks of each 8-week treatment period, the dose will be escalated toward a maximal tolerated dose or the target ceiling dose of 3600 mg/d, whichever is reached first. Matching placebo capsules will be similarly administered. An investigational new drug (IND) application will be filed with the FDA.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	120
Estimated Completion Date	March 2015
Estimated Primary Completion Date	March 2015
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). 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%]), (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 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 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
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	Accepts Healthy Volunteers
Contacts	Contact: Leslie Rawlinson 901-448-6693 lrawlins@uthsc.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01301001
Other Study ID Numbers	CSBrown Vulvodynia
Has Data Monitoring Committee	Yes
Information Provided By	University of Tennessee
Study Sponsor	University of Tennessee
Collaborators	University of Tennessee Health Science Center
Investigators	Principal Investigator: Candace S Brown, MSN, PharmD University of Tennessee Health Science CenterPrincipal Investigator: David C Foster, M.D. University of Rochester School of Medicine and DentistryPrincipal Investigator: Gloria A Bachmann, M.D. Rutgers - Robert Wood Johnson Medical School
Verification Date	December 2013

Locations[ + expand ][ + ]

Rutgers - Robert Wood Johnson Medical School	New Brunswick, New Jersey, United States, 08901-1962 Contact: Gloria A Bachmann, M.D. \| 732-235-7353 \| bachmaga@umdnj.edu Principal Investigator: Gloria A Bachmann, M.D. Recruiting
University of Rochester School of Medicine and Dentistry	Rochester, New York, United States, 14642-0002 Contact: David C Foster, M.D. \| 585-273-3232 \| David_Foster@URMC.Rochester.edu Principal Investigator: David C Foster, M.D. Recruiting
Clinical Research Center	Memphis, Tennessee, United States, 38104 Contact: Candace S Brown, MSN, PharmD \| 901-448-6044 \| csbrown@uthsc.edu Principal Investigator: Candace S Brown, MSN, PharmD Recruiting