Vulvodynia
Conditions
Keywords
Vulvodynia
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.
Interventions
DRUGPlacebo oral capsule
Placebo 2 capsules am and 3 capsules pm
DRUGGabapentin
Gabapentin 1200 mg am and 1800 mg pm
Sponsors
University of Tennessee
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tampon Test Pain Intensity | Week 6 for each treatment arm | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Coital Pain | Week 6 of each treatment arm | 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. |
| Vulvodynia Pain | Week 6 for each treatment arm | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited between August 8, 2012 and January 19, 2016 from three academic centers.
Pre-assignment details
230 women were screened, 89 met entry criteria and 66 completed the trial. Of the 141 patients who were excluded prior to randomization, 16 decided not to participate in the trial,101 did not meet inclusion criteria, and 24 did not return for randomization.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants 44 subjects were randomized to Placebo First and 45 subjects were randomized to Gabapentin First | 89 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 5 | 0 |
| First Intervention | Lost to Follow-up | 4 | 4 |
| First Intervention | Protocol Violation | 0 | 1 |
| First Intervention | Withdrawal by Subject | 1 | 4 |
| Second Intervention | Adverse Event | 2 | 0 |
| Second Intervention | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 36.54 years STANDARD_DEVIATION 2.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 58 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 89 participants |
| Sex/Gender, Customized Female | 89 Participants |
| Sex/Gender, Customized Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 89 | 0 / 89 |
| other Total, other adverse events | 20 / 89 | 31 / 89 |
| serious Total, serious adverse events | 1 / 89 | 0 / 89 |
Outcome results
Primary
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).
Time frame: Week 6 for each treatment arm
Population: Intention to Treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Tampon Test Pain Intensity | 4.29 units on a scale |
| Gabapentin | Tampon Test Pain Intensity | 3.96 units on a scale |
p-value: 0.0795% CI: [-0.7, 0]Mixed Models Analysis
Secondary
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.
Time frame: Week 6 of each treatment arm
Population: Intent to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Coital Pain | 3.97 units on a scale |
| Gabapentin | Coital Pain | 3.85 units on a scale |
p-value: 0.7695% CI: [-0.9, 0.6]Mixed Models Analysis
Secondary
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.
Time frame: Week 6 for each treatment arm
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Vulvodynia Pain | 2.88 units on a scale |
| Gabapentin | Vulvodynia Pain | 2.71 units on a scale |
p-value: 0.3695% CI: [-0.5, 0.2]Mixed Models Analysis