Clobetasol Propionate Versus Fractionated Carbon Dioxide Laser for the Treatment of Lichen Sclerosus (CuRLS)
Primary Purpose
Vulvar Lichen Sclerosus
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Fractionated Carbon Dioxide Laser
Clobetasol Propionate 0.05% ointment
Sponsored by
About this trial
This is an interventional treatment trial for Vulvar Lichen Sclerosus focused on measuring Vulva, Lichen Sclerosus, Fractionated Carbon Dioxide Laser, Mona Lisa Laser, Clobetasol Propionate, Vulvodynia
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
Sites / Locations
- Medstar Washington Hospital Center Lafayette Office
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Prior Clobetasol Exposure
No Prior Clobetasol Exposure
Arm Description
Patients with biopsy proven lichen sclerosus previously treated with clobetasol propionate
Patients with biopsy proven lichen sclerosus never previously treated with clobetasol propionate.
Outcomes
Primary Outcome Measures
Change in SkinDEX-29 Score
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
Change in Subjective Vulvovaginal Symptoms Questionnaire (VSQ)
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.
Change in Subjective Vulvovaginal Symptoms Questionnaire (VSQ)
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
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.
Number of Participants Considered Satisfied as Assessed by Health Related Quality of Life (HRQOL) Score
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
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 Vaginal Health Index (VHI) Score
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
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.
Change Vulvar Symptom Visual Analog Scale (VAS) Score
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
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
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.
Change Objective Provider VAS Visual Analog Scale
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
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
Number of Patients With Adverse Outcomes
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.
Number of Patients With Adverse Outcomes
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.
Full Information
NCT ID
NCT02573883
First Posted
October 7, 2015
Last Updated
October 6, 2021
Sponsor
Medstar Health Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT02573883
Brief Title
Clobetasol Propionate Versus Fractionated Carbon Dioxide Laser for the Treatment of Lichen Sclerosus
Acronym
CuRLS
Official Title
A Randomized Trial of Clobetasol Propionate Versus Fractionated CO2 Laser for the Treatment of Lichen Sclerosus (CuRLS)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
October 2015 (undefined)
Primary Completion Date
September 2019 (Actual)
Study Completion Date
September 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medstar Health Research Institute
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vulvar Lichen Sclerosus
Keywords
Vulva, Lichen Sclerosus, Fractionated Carbon Dioxide Laser, Mona Lisa Laser, Clobetasol Propionate, Vulvodynia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prior Clobetasol Exposure
Arm Type
Experimental
Arm Description
Patients with biopsy proven lichen sclerosus previously treated with clobetasol propionate
Arm Title
No Prior Clobetasol Exposure
Arm Type
Active Comparator
Arm Description
Patients with biopsy proven lichen sclerosus never previously treated with clobetasol propionate.
Intervention Type
Device
Intervention Name(s)
Fractionated Carbon Dioxide Laser
Other Intervention Name(s)
SmartXide -V2-LR system, Mona Lisa Laser
Intervention Description
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
Drug
Intervention Name(s)
Clobetasol Propionate 0.05% ointment
Other Intervention Name(s)
Temovate Propionate 0.05% ointment
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in SkinDEX-29 Score
Description
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).
Time Frame
Change from baseline score to score at six months
Secondary Outcome Measure Information:
Title
Change in Subjective Vulvovaginal Symptoms Questionnaire (VSQ)
Description
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.
Time Frame
Baseline to six months
Title
Change in Subjective Vulvovaginal Symptoms Questionnaire (VSQ)
Description
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.
Time Frame
Six month to one year after treatment
Title
Number of Participants Considered Satisfied as Assessed by Health Related Quality of Life (HRQOL) Score
Description
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.
Time Frame
Six months from treatment
Title
Number of Participants Considered Satisfied as Assessed by Health Related Quality of Life (HRQOL) Score
Description
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.
Time Frame
1 year from treatment
Title
Change Vaginal Health Index (VHI) Score
Description
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.
Time Frame
Baseline to 6 months after treatment
Title
Change Vaginal Health Index (VHI) Score
Description
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.
Time Frame
Six month to one year after treatment
Title
Change Vulvar Symptom Visual Analog Scale (VAS) Score
Description
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.
Time Frame
Baseline to 6 months after treatment
Title
Change Vulvar Symptom Visual Analog Scale (VAS) Score
Description
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).
Time Frame
Six months to one year after treatment
Title
Change SkinDEX-29 Score
Description
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.
Time Frame
Six months to one year from treatment
Title
Change Objective Provider VAS Visual Analog Scale
Description
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.
Time Frame
Baseline to Six months from treatment
Title
Change Objective Provider VAS Visual Analog Scale
Description
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.
Time Frame
Six months to One Year from treatment
Title
Number of Patients With Adverse Outcomes
Description
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
Time Frame
Six Month to One Year from treatment
Title
Number of Patients With Adverse Outcomes
Description
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.
Time Frame
12 Weeks to Six months from treatment
Title
Number of Patients With Adverse Outcomes
Description
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.
Time Frame
12 Weeks from treatment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cheryl Iglesia, MD
Organizational Affiliation
Medstar Health Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medstar Washington Hospital Center Lafayette Office
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22161424
Citation
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.
Results Reference
background
PubMed Identifier
24605832
Citation
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.
Results Reference
background
PubMed Identifier
25539748
Citation
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.
Results Reference
background
PubMed Identifier
33957642
Citation
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.
Results Reference
derived
Learn more about this trial
Clobetasol Propionate Versus Fractionated Carbon Dioxide Laser for the Treatment of Lichen Sclerosus
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