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

NCT ID: NCT02573883

Last Updated: 2021-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2019-09-30

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.

Conditions

Vulvar Lichen Sclerosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Prior Clobetasol Exposure

Patients with biopsy proven lichen sclerosus previously treated with clobetasol propionate

Group Type: EXPERIMENTAL

Fractionated Carbon Dioxide Laser

Intervention Type: DEVICE

Vulvar lichen sclerosis will be treated except for the clitoris glans and clitoral hood which will be spared with at least 5mm margin. The procedure will be performed in the outpatient clinic at the National Center for Advanced Pelvic Surgery at MedStar Washington Hospital Center Lafayette Office, 1133 21st St NW, Washington, DC 20036, and include 3 sessions, 4 weeks apart.

Clobetasol Propionate 0.05% ointment

Intervention Type: DRUG

Topical Steroid therapy (Clobetasol propionate .05% ointment nightly for one month then three times weekly for 2 additional months) for a total of three months of treatment.

No Prior Clobetasol Exposure

Patients with biopsy proven lichen sclerosus never previously treated with clobetasol propionate.

Group Type: ACTIVE_COMPARATOR

Fractionated Carbon Dioxide Laser

Intervention Type: DEVICE

Vulvar lichen sclerosis will be treated except for the clitoris glans and clitoral hood which will be spared with at least 5mm margin. The procedure will be performed in the outpatient clinic at the National Center for Advanced Pelvic Surgery at MedStar Washington Hospital Center Lafayette Office, 1133 21st St NW, Washington, DC 20036, and include 3 sessions, 4 weeks apart.

Clobetasol Propionate 0.05% ointment

Intervention Type: DRUG

Topical Steroid therapy (Clobetasol propionate .05% ointment nightly for one month then three times weekly for 2 additional months) for a total of three months of treatment.

Interventions

Fractionated Carbon Dioxide Laser

Vulvar lichen sclerosis will be treated except for the clitoris glans and clitoral hood which will be spared with at least 5mm margin. The procedure will be performed in the outpatient clinic at the National Center for Advanced Pelvic Surgery at MedStar Washington Hospital Center Lafayette Office, 1133 21st St NW, Washington, DC 20036, and include 3 sessions, 4 weeks apart.

Intervention Type: DEVICE

Clobetasol Propionate 0.05% ointment

Topical Steroid therapy (Clobetasol propionate .05% ointment nightly for one month then three times weekly for 2 additional months) for a total of three months of treatment.

Intervention Type: DRUG

Other Intervention Names

SmartXide -V2-LR system; Mona Lisa Laser; Temovate Propionate 0.05% ointment

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Medstar Health Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cheryl Iglesia, MD

Role: PRINCIPAL_INVESTIGATOR

Medstar Health Research Institute

Locations

Medstar Washington Hospital Center Lafayette Office

Washington D.C., District of Columbia, United States

Countries

United States

References

Chi CC, Kirtschig G, Baldo M, Brackenbury F, Lewis F, Wojnarowska F. Topical interventions for genital lichen sclerosus. Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD008240. doi: 10.1002/14651858.CD008240.pub2.

Reference Type: BACKGROUND

PMID: 22161424 (View on PubMed)

Salvatore S, Nappi RE, Zerbinati N, Calligaro A, Ferrero S, Origoni M, Candiani M, Leone Roberti Maggiore U. A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric. 2014 Aug;17(4):363-9. doi: 10.3109/13697137.2014.899347. Epub 2014 Jun 5.

Reference Type: BACKGROUND

PMID: 24605832 (View on PubMed)

He Z, Lu C, Chren MM, Zhang Z, Li Y, Ni X, Buchtel V HA, Ryan PF, Li GZ. Development and psychometric validation of the Chinese version of Skindex-29 and Skindex-16. Health Qual Life Outcomes. 2014 Dec 24;12:190. doi: 10.1186/s12955-014-0190-4.

Reference Type: BACKGROUND

PMID: 25539748 (View on PubMed)

Burkett LS, Siddique M, Zeymo A, Brunn EA, Gutman RE, Park AJ, Iglesia CB. Clobetasol Compared With Fractionated Carbon Dioxide Laser for Lichen Sclerosus: A Randomized Controlled Trial. Obstet Gynecol. 2021 Jun 1;137(6):968-978. doi: 10.1097/AOG.0000000000004332.

Reference Type: DERIVED

PMID: 33957642 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2016-154

Identifier Type: -

Identifier Source: org_study_id