Clobetasol Propionate Versus Fractionated Carbon Dioxide Laser for the Treatment of Lichen Sclerosus

Phase 3

Completed

Conditions: Vulvar Lichen Sclerosus

Interventions: Device: Fractionated Carbon Dioxide Laser
Drug: Clobetasol Propionate 0.05% ointment

Registration Number: NCT02573883

Lead Sponsor: Medstar Health Research Institute

Brief Summary: This study is being done to compare the effects, good and bad, of fractionated CO2 laser treatment and clobetasol propionate .05% ointment on vulvar lichen sclerosus.

Detailed Description: Vulvar lichen sclerosus (LS) is a well-characterized dermatosis resulting in labial atrophy, synechiae and introital narrowing and can often cause dyspareunia, itching and co-existent vulvar pain. Biopsy is necessary to confirm the clinical diagnosis and the mainstay of treatment usually consists of topical steroid therapy (Chi). Clobetasol propionate and mometasone furoate are potent topical steroids that have long been considered gold-standard treatment for vulvar lichen sclerosus and work through anti-inflammatory, anti-mitotic, and immunosuppressive effects. One of the complications of long-term steroid use, however, is potential thinning of the vulvar skin, therefore limiting long-term use. Clobetasol propionate has a range of efficacy from 61-91% depending on the selected outcome criteria.

The vulvovaginal SmartXide -V2-LR laser system by DEKA (Calezano, Italy) is a fractionated C02 laser with maximum 40 Watt power and laser energy emission at 10,600 nanometer wavelength which is mainly absorbed by water in the underlying tissue (Salvatore). The SmartXide-V2-LR system was first introduced in 2009 with DOT therapy distributing fractioned CO2 laser in small spots of 200 microns to the vulvar skin or vaginal epithelium, resulting in a portion of the skin remaining intact with less tissue destruction and faster healing (Salvatore). The device is cleared by the US Food and Drug Administration (FDA) for incision, excision, ablation, and coagulation of gynecologic soft tissues. The fractioned therapy has been shown to stimulate fibroblastic growth through activation and biosynthesis of collagen and restoration of the extracellular matrix with collagen fibers.

Very little is known about long-term effects of fractionated C02 laser therapy use in the vulva or vagina, although the treatment is widely accepted in plastic and cosmetic surgery and dermatology. Increased marketing for laser vaginal rejuvenation has spawned a proprietary female genital cosmetic surgery industry in the US with very limited published outcome data. SmartXide -V2-LR has some established outcome data for treatment of genitourinary syndrome of menopause (GSM), also known as vulvovaginal atrophy (Salvatore).

The purpose of this study is to compare the safety and efficacy of clobetasol propionate .05% ointment to fractionated CO2 laser procedure for the treatment of vulvar lichen sclerosus. Women presenting to the urogynecology clinic will be screened for lichen sclerosus. Vulvar biopsy will be performed for confirmation, and, if eligible, the patient will be consented to undergo baseline questionnaires, photodocumentation of vulvar lesions and randomization. A minimum of 2 weeks are required from the time of biopsy to treatment. Patient will be randomized to monthly LASER treatment for 3 months or topical STEROID therapy (clobetasol propionate .05% ointment nightly for one month then three times weekly for 2 additional months) in a 1:1 ratio using a computer generated randomization schedule. Because of the nature of the treatment, it will not be possible to blind patients but the assessor will be blinded to the intervention. Patients may have used clobetasol propionate in past, but must complete 8 week wash out period.

Patient questionnaires include multiple validated scales and surveys to provided reproducible measures of vulvar symptoms as primary and secondary outcomes. Questionnaires will be completed at the intake visit, repeated at 6 month and one year follow up. The investigators expect improved subjective and objective results in the LASER group at 6 months compared with the STEROID group. At 6 months, participants are giving the option to crossover to receive the other treatment arm if desired due to continued symptoms. All groups are followed to 12 months for comparison.

Sample size calculations were conducted using the absolute change in the Skindex 29 as the primary end point. Out study will reach 80% power to detect a mean difference of 16 points on the Skindex 29 (sd=22 for both groups) between the study groups with 25 patients in each group, or 50 in total based on a one-sided two-sample t-test with alpha=0.05 (He). By accounting for 10% attrition, the investigators propose to recruit 56 patients to the study to be randomized with a 1:1 ratio to each group, with a blocked component for those who used tropical clobetasol in the past.

Data will be entered into a secure RedCAPS Database which provides complete auditing for data management processes. De-identified backup data will be kept in locked files at the participating site. Plans for publication will be handled by the investigators at MedStar Washington Hospital Center and will adhere to publication policies. All personnel with access to data collected have completed the Program for Ethics Education in Research training with the appropriate HIPAA certification.

Patients will not be compensated for travel and may be accountable for some medical bills for office visits. Study location is Medstar Lafayette Office 1133 21st St NW, Washington, DC 20036.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 52

Inclusion Criteria

Biopsy proven symptomatic vulvar lichen sclerosus
Ability to understand the study, accept randomization and logistically follow-up with scheduled visits
English Speaking

Exclusion Criteria

Known vulvar malignancy
Pregnancy or planning pregnancy or less than 3 months postpartum
Premenopausal
Current or prior diagnosis of any gynecologic malignancy
Previous pelvic radiation therapy
Allergy to topical steroid
Active Urinary Tract Infection (UTI), vulvar infection (candida, herpes, bacterial vaginosis, trichomoniasis or other infection)
Pelvic organ prolapse > than Stage 2
Treatment with systemic immunomodulators, topical calcineurin inhibitors (tacrolimus, pimecrolimus), or vaginal hormonal or vulvar topical steroid use within 2 months of enrollment
History of transvaginal mesh implant (excluding sling or sacrocolpopexy mesh)
IUD (Intrauterine Device)
Skindex-29 overall score <21, below mildly impaired health related quality of life threshold

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Prior Clobetasol Exposure	Fractionated Carbon Dioxide Laser	Patients with biopsy proven lichen sclerosus previously treated with clobetasol propionate
Prior Clobetasol Exposure	Clobetasol Propionate 0.05% ointment	Patients with biopsy proven lichen sclerosus previously treated with clobetasol propionate
No Prior Clobetasol Exposure	Fractionated Carbon Dioxide Laser	Patients with biopsy proven lichen sclerosus never previously treated with clobetasol propionate.
No Prior Clobetasol Exposure	Clobetasol Propionate 0.05% ointment	Patients with biopsy proven lichen sclerosus never previously treated with clobetasol propionate.

Primary Outcome Measures

Name	Time	Method
Change in SkinDEX-29 Score	Change from baseline score to score at six months	The Skindex-29 is a validated questionnaire for assessing acute dermatologic symptoms over a 4-week period. The Skindex-29 is a 29 question version of the original SkinDEX questionnaire. Total numeric score is reported ranging from 0-100. Scores reported as a change between six months and baseline with more negative scores indicating greater improvement in symptoms (better outcome).

Secondary Outcome Measures

Name	Time	Method
Change in Subjective Vulvovaginal Symptoms Questionnaire (VSQ)	Six month to one year after treatment	Subjective measure of vulvar symptoms of itching, burning, dyspareunia of Lichen Sclerosus. VSQ is a 21-item instrument and scores range from 0 to 20 with increased scores indicating increased vulvovaginal symptom bother. The change in VSQ is reported with more negative scores indicating greater improvement.
Number of Participants Considered Satisfied as Assessed by Health Related Quality of Life (HRQOL) Score	1 year from treatment	Patient global impression of satisfaction total score on visual analog scale (very satisfied or satisfied) ranging from 1-5 with higher scores indicating greater satisfaction.
Change Vaginal Health Index (VHI) Score	Six month to one year after treatment	The Vaginal Health Index is a five item scale with scores ranging from 5-25 with lower scores indicating greater urogenital atrophy. The change in VHI is express with more negative scores indicating greater improvement between study time points.
Change Vulvar Symptom Visual Analog Scale (VAS) Score	Six months to one year after treatment	Patient subjective scale of symptoms of Lichen Sclerosus. Each item scaled 0-10 with greater severity of symptoms indicated by higher score. Results expressed as change with more negative values indicating greater improvement in symptoms (better outcome).
Change SkinDEX-29 Score	Six months to one year from treatment	The Skindex-29 is a validated questionnaire for assessing acute dermatologic symptoms over a 4-week period. The Skindex-29 is a 29 question version of the original SkinDEX questionnaire. Total numeric score is reported ranging from 0-100. Scores reported as a change between six months and baseline with more negative scores indicating greater improvement.
Change Objective Provider VAS Visual Analog Scale	Six months to One Year from treatment	Provider scored objective appearance of vulvar Lichen Sclerosus. Each item scaled 0-10 with greater severity of appearance indicated by higher score. Results expressed as change with more negative values indicating greater improvement.
Number of Patients With Adverse Outcomes	12 Weeks from treatment	Total number for adverse outcomes (of any severity) to include description of pain, infection, de novo or worsening dyspareunia, contact dermatitis and burns from treatment.