Clinical trial NCT05010421: Laser Vs Clobetasol for Lichen Sclerosus
Official title: CO2 Non-ablative Laser Versus Topical Clobetasol for Lichen Sclerosus: a Prospective, Open-label, Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lichen Sclerosus
Keywords: Lichen Sclerosus
Laser
Clobetasol
Corticosteroids
Lead sponsor: Ruhr University of Bochum
Sponsor class: OTHER
First posted: 2021-08-18
Enrollment: 198
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized open single center study
Primary purpose: TREATMENT

Brief summary: Lichen sclerosus (LS) is a common autoimmune disease of the genital skin. It affects 1/900 women with an age peak in the sixth decade of life and is manifested by chronic inflammation of the genital, perineal, and perianal areas associated with itching, burning, pain, and soreness. In addition, LS is associated with an increased risk of vulvar cancer.

Treatment options for LS include topical steroids such as clobetasol, immunomodulators such as tacrolimus, and non-ablative laser treatment. Although both treatments are well documented and used in clinical practice, direct comparative studies of the efficacy of topical corticosteroids versus laser treatment in women with LS are rare. For example, a PubMed literature search (search date 2021-03-14; search terms: lichen sclerosus, laser, corticosteroids, steroids, clobetasol, randomized) identified only a single randomized trial with limited power.

Given the available evidence, further high-quality studies are needed to define the superiority/inferiority of the different available treatment options such as nonablative lasers and topical corticosteroids.

Therefore, in this prospective, randomized, open-label, comparative study, treatment success after 3 courses of non-ablative treatment with CO2 laser every 14 days will be compared with treatment success after topical application of clobetasol 0.05% over 3 months (daily in the first month, every other day in month 2, and 3 times/week during month 3) at the time point 3 months after treatment initiation.

Detailed description: Lichen sclerosus (LS) is a common autoimmune disorder of the genital skin. It affects 1/900 women with an age peak in the sixth decade of life. LS is a chronic inflammatory condition affecting the genital, perineal, and perianal areas and causes itching, burning, pain, and soreness. Histologically, LS is characterized by epidermal atrophy, hyperkeratosis, follicular plugging, degeneration of the basal layer, and subepidermal hyalinization of collagen in the papillary dermis with a lymphocytic infiltrate. Affected women typically suffer significant long-term genital damage including scarring, fusion of the vulval labia, narrowing of the vaginal opening, dyspareunia, and burying of the clitoris. In addition, LS is associated with an increased risk of vulvar cancer.

Treatment options of LS include topical steroids such as clobetasol, topical immunomodulators such as tacrolimus, and non-ablative laser treatment. In a systematic review of the literature with 7 studies and 249 participants, clobetasol achieved improvement rates and remission rates of 70% to 89% and 20% to 35%, respectively. In comparison, non-ablative laser treatment leads to significant improvements in vulvar itching, dryness, pain, and dyspareunia in 50% to 85% of women with remission rates of up to 80% after 14 years of follow-up. Although both treatments are well documented and used in clinical practice, direct comparative studies assessing the efficacy of topical corticosteroids versus laser treatment in women with LS are rare. For example, in a PubMed literature search (search date 2021-03-14; search terms: lichen sclerosus, laser, corticosteroids, steroids, clobetasol, randomized) only one randomized trial was identified. In this study, the authors included 40 women with LS and compared 3 applications of non-ablative laser 2 weeks apart with 4 weeks of twice daily (2 weeks), once daily (1 week), and every other day (1 week) of topical clobetasol 0.05% cream. After 3 months of treatment laser-treated women had a significantly higher sum score (including burning, itching, and pain) measured on an 11-step visual analogue scale (VAS). Both treatments demonstrated histological improvement with reductions of inflammatory hallmarks in skin biopsies.

Given this body of evidence, more high-quality studies are needed to define the superiority/inferiority of the different available treatment options such as non-ablative laser and topical corticosteroids. Therefore, a prospective, randomized trial comparing non-ablative CO2 laser treatment and topical clobetasol 0.05% will be conducted. The aim of this prospective, randomized, open-label, comparative trial is to establish or refute the superiority of 3 courses of non-ablative treatment by CO2 laser every 14 days compared to topical clobetasol 0.05% (daily in month 1, every other day in month 2, and 3 times/week in month 3) for 3 months. The primary endpoint of this study is a sum score including the pathognomonic symptoms of LS, namely vulvar burning, itching, and pain, each measured on an 11-step VAS. Secondary endpoints will include the physician-scored rate of visual improvement (measured on an 11-item VAS), side effects, and patient-reported outcomes such as subjective overall improvement, general satisfaction, and quality of life (measured by a validated questionnaire for vulval disorders; i.e. the VDQI (Vulval Disease Quality of Life Index).

Eligibility criteria: Inclusion Criteria:

* Women, age ≥ 18 years
* Established diagnosis of LS (vulva and/or perineum and/or perianal region)
* Willingness to comply with study requirements
* No significant language barrier

Exclusion Criteria:

* Concurrent immunosuppressive treatment
* A history of vulvar cancer and/or vulvar dysplasia
* A history of vulvar surgery
* A contraindication against clobetasol treatment
* A known sun light allergy
* A known skin condition interfering with local ablative treatment such as neurodermatitis or bullous pemphigoid

Primary outcomes:
measure: Vulvar burning, itching, and pain
timeFrame: from date of randomization until 12 weeks
Secondary outcomes:
measure: Efficacy - Physician-scored rate of visual improvement (0-10)
timeFrame: 3 months after treatment start
measure: Safety - Number and severity of side effects
timeFrame: 0-7 days after laser treatment (laser group); as well as throughout study duration (3 months; both groups)
measure: Subjective overall improvement (0-10)
timeFrame: 3 months after treatment start
measure: Vulval Disease Quality of life Index (0-45)
timeFrame: Throughout study completion (3 months; for a total of 4 or 5 assessments, depending on group assignment)
Other outcomes:
Locations:
city: Herne
country: Germany
facility: Marien Hospital Herne
state: NRW
Study officials:
affiliation: Ruhr-Universität Bochum / Marien Hospital Herne
name: Clemens B Tempfer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bizjak Ogrinc U, Sencar S, Luzar B, Lukanovic A. Efficacy of Non-ablative Laser Therapy for Lichen Sclerosus: A Randomized Controlled Trial. J Obstet Gynaecol Can. 2019 Dec;41(12):1717-1725. doi: 10.1016/j.jogc.2019.01.023. Epub 2019 Apr 11.
citation: Felmingham C, Chan L, Doyle LW, Veysey E. The Vulval Disease Quality of Life Index in women with vulval lichen sclerosus correlates with clinician and symptom scores. Australas J Dermatol. 2020 May;61(2):110-118. doi: 10.1111/ajd.13197. Epub 2019 Nov 14.
citation: Murphy R. Lichen sclerosus. Dermatol Clin. 2010 Oct;28(4):707-15. doi: 10.1016/j.det.2010.07.006.
citation: Renaud-Vilmer C, Cavelier-Balloy B, Porcher R, Dubertret L. Vulvar lichen sclerosus: effect of long-term topical application of a potent steroid on the course of the disease. Arch Dermatol. 2004 Jun;140(6):709-12. doi: 10.1001/archderm.140.6.709.
citation: Chi CC, Kirtschig G, Baldo M, Lewis F, Wang SH, Wojnarowska F. Systematic review and meta-analysis of randomized controlled trials on topical interventions for genital lichen sclerosus. J Am Acad Dermatol. 2012 Aug;67(2):305-12. doi: 10.1016/j.jaad.2012.02.044. Epub 2012 Apr 6.
citation: Pagano T, Conforti A, Buonfantino C, Schettini F, Vallone R, Gallo A, Avino L, Alviggi C, De Placido G, Sopracordevole F. Effect of rescue fractional microablative CO2 laser on symptoms and sexual dysfunction in women affected by vulvar lichen sclerosus resistant to long-term use of topic corticosteroid: a prospective longitudinal study. Menopause. 2020 Apr;27(4):418-422. doi: 10.1097/GME.0000000000001482.