Fractionated CO2 Laser With and Without Clobetasol for Treatment of Vulvar Lichen Sclerosus

Study Overview
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Brief Summary
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This is a randomized placebo-controlled trial design to determine whether combining FxCO2-laser with the traditional therapy of clobetasol propionate 0.05% ointment (combined treatment) as compared to FxCO2-laser and placebo ointment (FxCO2-laser only) will improve treatment response in women undergoing FxCO2-laser for vulvar lichen sclerosus. Primary objective: To evaluate if women with LS who undergo FxCO2 laser therapy and concomitant TCS (clobetasol group) have higher treatment success (defined as a MCID of a ≥16 point improvement in Skindex-29 questionnaire) than those who undergo FxCO2 laser and placebo ointment (placebo group). Hypothesis: A higher proportion of women randomized to clobetasol will achieve treatment success as compared to those randomized to placebo. Approach: The proportion of women in each cohort who obtain a ≥16 point improvement in Skindex-29 validated questionnaire score from baseline to final visit will be compared. Secondary objectives: To compare change in pre- and post-treatment scores on validated questionnaires measuring vulvovaginal symptoms, sexual function, lower urinary tract function, and genital self-image between the clobetasol group compared to the placebo group. Hypothesis: Women randomized to clobetasol will demonstrate an equal or greater improvement on validated quality of life questionnaires measuring vulvovaginal symptoms, sexual function, lower urinary tract function, and genital self-image as compared to women randomized to placebo. Approach: Change scores will be calculated to determine change per participant over the treatment period and mean change scores will be compared between cohorts.

Official Title
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A Randomized Controlled Trial of Vulvar Fractionated CO2-Laser Therapy With and Without Concomitant Topical Clobetasol Propionate 0.05% Ointment for Treatment of Vulvar Lichen Sclerosus

Conditions
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Vulvar Lichen Sclerosus

Intervention / Treatment
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* Device: Fractionated CO2-laser
* Drug: Clobetasol Propionate 0.05% Ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥ 18 years old with biopsy confirmed or clinically diagnosed+ LS English-speaking or Spanish-speaking Electing to undergo Fractionated CO2-laser therapy Willing and able to undergo concomitant 0.05% clobetasol propionate treatment Exclusion Criteria: Prior surgery with placement vaginal mesh for repair of pelvic organ prolapse (does not include vaginal mesh for anti-incontinence procedure sling or prior mesh sacrocolpopexy) Prior laser, topical immunomodulators or systemic therapy for LS Active genital infection^ Suspicious vulvar lesion that has not been evaluated Known vulvar or vaginal malignancy or active treatment for other malignancy Planning pregnancy or pregnant Prior pelvic radiation therapy Topical corticosteroid use on the vulvovaginal tissues in the past 2 weeks* Contraindication or allergy to clobetasol propionate 0.05% Currently breast-feeding or lactating History of poor wound healing, keloids or hypertrophic scarring History of a skin condition that could interfere with evaluation of efficacy and safety Eligible for inclusion after washout period of 2 weeks ^Eligible for inclusion after treatment. For patients with known genital HSV we will instruct them to remain on suppression for the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clobetasol Group<br>Clobetasol propionate 0.05% ointment is the active treatment arm that will be use in women with lichen sclerosus in the study per standard clinical recommendations. Participants will be instructed to apply 0.25-0.5g of the ointment to the affected tissues nightly for 4 weeks starting after the initial FxCO2 laser treatment, then 2 times a week for the remainder of the study (until final study visit). | Device: Fractionated CO2-laser<br>* All women will be undergoing FxCO2-laser therapy as this treatment is a criterion for enrollment.<br>Drug: Clobetasol Propionate 0.05% Ointment<br>* Clobetasol propionate 0.05% ointment obtained from a commercial manufacturer<br>* Other names: Clobetasol;|
| Placebo Comparator: Placebo Group<br>Placebo ointment is the control treatment arm. Participants will be instructed to apply 0.25-0.5g of the ointment to the affected tissues nightly for 4 weeks starting after the initial FxCO2 laser treatment, then 2 times a week for the remainder of the study (until final study visit). | Device: Fractionated CO2-laser<br>* All women will be undergoing FxCO2-laser therapy as this treatment is a criterion for enrollment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment success | Minimally clinically important difference of a ≥16 point improvement in Skindex-29 validated questionnaire score. Skindex-29 responses are transformed to a linear scale from 0 (no effect) to 100 (effect experienced all the time), and are reported as three scale scores, corresponding to three domains (symptoms, emotions, and functioning). A reduction in Skindex-29 score of 16 points or more has been shown to indicate what is considered a clinically meaningful improvement. | About 5 months (baseline to final visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response - vulvovaginal symptoms | Treatment response - vulvovaginal symptoms will be measured by pre- and post-treatment scores on the vulvovaginal Symptoms Questionnaire, a 21-item survey measuring vulvovaginal symptoms in postmenopausal women. | About 5 months (baseline to final visit) | 
| Treatment response - sexual function | Treatment response - sexual function will be measured by pre- and post-treatment scores on the Female Sexual Function Index, a validated questionnaire to assess sexual function. | About 5 months (baseline to final visit) | 
| Treatment response - genital self image | Treatment response - genital self image will be measured by pre- and post-treatment scores on the Female Genital Self Image Scale, a validated survey with scores ranging from 7-28 with higher scores indicate a more positive genital self-image. | About 5 months (baseline to final visit) | 
| Treatment response - lower urinary tract function | Treatment response - lower urinary tract function will be measured by pre- and post-treatment scores on the LURN SI-10, a 10-item questionnaire with scores ranging from 0 to 38 (higher scores = worse symptoms/bother). | About 5 months (baseline to final visit) | 
| Participant-perceived improvement | Patient Global Impression of Improvement (PGI-I): a one single item question that will ask participants to rate their improvement after undergoing treatment on a 7-point Likert scale ranging from very much worse to very much better. | Final study visit at 4-6 weeks after third Fractionated CO2 laser treatment - one time question | 
| Participant-perceived treatment satisfaction | Level of satisfaction with treatment: a one single item question that will ask participants to rate their level of satisfaction with treatment on a 5-point Likert scale from very dissatisfied to very satisfied. | Final study visit at 4-6 weeks after third Fractionated CO2 laser treatment - one time question | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clobetasol propionate, Fractionated CO2-laser