The CO2RE® System for Vulvar Lichen Sclerosus

Clinical Study of the CO2RE® Laser Device for Treatment of Vulvar Lichen Sclerosus

Subjects with vulvar lichen sclerosus (VLS) will undergo fractional carbon dioxide (CO2) laser treatment to the vulvar area. Subjects will be evaluated for changes in clinical signs and architectural changes associated with VLS at designated follow-ups to 1-year post treatment series.

Study Overview

• Status: Completed
• Conditions: Vulvar Lichen Sclerosus
• Intervention / Treatment: Device: The CO2RE® System

Detailed Description

This study is a prospective, non-randomized, single-group assignment, interventional clinical trial. Female subjects with vulvar lichen sclerosus (VLS) supported by histologic findings on biopsy and/or clinical signs on physical examination and recalcitrant to mid- to high-potency steroid therapy, will undergo up to 5 monthly treatments to the vulva with a fractional CO2 laser.

Investigators will assess clinical signs and architectural changes associated with VLS. Baseline measurements will be compared to follow-up at 6 weeks, 3 months, 6 months and 12 months after the final treatment.

Subjects will self report sexual function using a validated FSFI Questionnaire at baseline and at the 3- and 6-month follow-ups.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Total Dermatology Care Center
    • Jacksonville, Florida, United States, 32207
      • Center for Modern Aesthetic Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • HERmd (formerly Somi Javaid M.D. & Associates)
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • Lumina Med Spa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Able to read, understand and sign informed consent for study participation;
2. Female subjects with age 18-80 years;
3. Biopsy demonstrates biopsy-proven lichen sclerosus and/or there are characteristic changes for vulvar lichen sclerosus on physical examination;
4. Treatment of LS has been recalcitrant to mid to high-potent topical corticosteroid treatment or subject refuses topical corticosteroid treatment. Recalcitrance to therapy is defined as no response to topical corticosteroids of an adequate potency (i.e. clobetasol propionate 0.05% ointment or other steroids) and a sufficient duration (12 weeks of use) or lack of symptomatic control of the disease with a maintenance therapy;
5. Topical corticosteroid treatment, if any, will be continued during the study period;
6. Exogenous hormone treatment, if any, will be continued during the study period (type and dose must stay consistent throughout the study);
7. One or more of the following symptoms: itch; pain unrelated to intercourse; pain, skin tearing or bleeding with intercourse; changes/decrease in sexual function;
8. No breaks, tears or lesions, malodorous discharge or strawberry cervix present on gynecological exam.

Exclusion Criteria:

1. Presence of clinically atypical appearing nevi in the area to be treated;
2. Unexplained vaginal bleeding;
3. Active infection, specifically: urinary tract infection, vulvar or vaginal infection (candidiasis, genital herpes/herpes simplex virus, bacterial vaginosis, trichomonas);
4. History of vulvar or any gynecological malignancy, as well as history of pelvic radiation therapy or stem cell transplant;
5. Pelvic organ prolapse > stage 2;
6. Pregnancy or planning pregnancy during the study;
7. Systemic treatment with immuno-modulatory drugs.
8. Use of vaginal dilators during study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CO2RE® Treatment; All eligible subjects will undergo up to 5 treatments at 4±1-week intervals to the vulva with a fractional CO2 laser.	Device: The CO2RE® System; The CO2RE® system is a fractional CO2 laser that is FDA-cleared under a 510(k) K181523 for laser incision, excision, ablation and/or vaporization and of soft tissue in gynecology (GYN) for the treatment of leukoplakia (vulvar dystrophies).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators	Each clinical sign of VLS (loss of elasticity, sclerosis, lichenification, whitening, parchment-like skin, fissures, extent of the disease, erosions, ulcerations, hyperkeratosis, excoriation, telangiectasia) was assessed separately by the investigator, using a 4-point scale (0=not present, 1=mild, 2=moderate or 3=severe) for each subject at baseline and follow-ups. For those clinical signs present at baseline (baseline score >0 on severity scale), an average severity grade was calculated at each endpoint to evaluate overall treatment outcome, as follows: Average severity grade = Sum of all severity grades (0, 1, 2, or 3) for each individual parameter of clinical signs present at baseline for each subject / Number of grades A lower average score means better outcome.	At Baseline, 3, 6 and 12 months after the final treatment
Average Scores for VLS Architectural Changes Present At Baseline and at 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators	Each architectural change of VLS (labial fusion, clitoral hood fusion, narrowing of the introitus, anterior changes, perianal involvement, formation of posterior commissure bands) was assessed separately by the investigator, using a 4-point scale (0=not present, 1=mild, 2=moderate or 3=severe) for each subject at baseline and follow-ups. For those architectural changes present at baseline (baseline score >0 on severity scale), an average severity grade was calculated at each endpoint to evaluate overall treatment outcome, as follows: Average severity grade = Sum of all severity grades (0, 1, 2, or 3) for each individual parameter of architectural changes present at baseline for each subject / Number of grades A lower average score means better outcome.	Baseline, 3 , 6 and 12 months after the final treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Sexual Function on the Female Sexual Function Index (FSFI) at 3 Months and 6 Months After the Final Treatment	Female Sexual Function Index (FSFI) is a validated, self-reported 19-item questionnaire that assesses domains of sexual function, including desire, arousal, lubrication, orgasm, satisfaction, and pain. The aggregated FSFI score is a sum of weighted answers for each of the 19 items in the questionnaire, with a maximum total score possible of 36.0 (high level of sexual functional) and minimum score of 2.0 (low level of sexual functional). Change = (Follow-up score - Baseline score). Mean change was calculated for all scores at the 3- and 6-month follow-ups.	Baseline and 3 months and 6 months after the final treatment
Subject Satisfaction At the 12-Month Follow-up	Evaluate Subject satisfaction at the 12 months post-last treatment visit, using a satisfaction scale [(-2) Very dissatisfied, (-1) Dissatisfied, (0) Uncertain, (1) Satisfied, (2) Very satisfied]. The analysis quantify the percentage of Subject satisfaction (score 1 or 2) at the 12-month follow-up.	12 months after the final treatment
Treatment Associated Pain Score	Subjects underwent 3-5 monthly treatments and reported discomfort associated with treatment on a 10-cm visual analogue scale (VAS) of 0 = no pain to 10 = worst possible pain, immediately after each treatment. The outcome presented here is the mean grade of discomfort/pain associated with all treatments. Lower value presents lower treatment-associated discomfort. Since patients received 3-5 monthly treatments these values were collected at each treatment over a period of 2 to 4 months for each patient.	Immediately after the 1st, 2nd, 3rd, 4th and 5th monthly treatments post baseline

Collaborators and Investigators

• Sponsor: Candela Corporation
• Investigators: Study Director: Konika P Schallen, MD, Candela Corporation

Publications and helpful links

General Publications

• Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D, D'Agostino R Jr. The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000 Apr-Jun;26(2):191-208. doi: 10.1080/009262300278597.
• Salvatore S, Leone Roberti Maggiore U, Athanasiou S, Origoni M, Candiani M, Calligaro A, Zerbinati N. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause. 2015 Aug;22(8):845-9. doi: 10.1097/GME.0000000000000401.
• Thorstensen KA, Birenbaum DL. Recognition and management of vulvar dermatologic conditions: lichen sclerosus, lichen planus, and lichen simplex chronicus. J Midwifery Womens Health. 2012 May-Jun;57(3):260-75. doi: 10.1111/j.1542-2011.2012.00175.x.
• Sheinis M, Selk A. Development of the Adult Vulvar Lichen Sclerosus Severity Scale-A Delphi Consensus Exercise for Item Generation. J Low Genit Tract Dis. 2018 Jan;22(1):66-73. doi: 10.1097/LGT.0000000000000361.
• Stewart K, Javaid S, Schallen KP, Bartlett S, Carlson NA. Fractional CO2 laser treatment as adjunctive therapy to topical steroids for managing vulvar lichen sclerosus. Lasers Surg Med. 2022 Jan;54(1):138-151. doi: 10.1002/lsm.23476. Epub 2021 Sep 20.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2018
• Primary Completion (Actual): July 30, 2020
• Study Completion (Actual): December 17, 2020

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: hyperkeratosis; sexual function; leukoplakia; vulvar dystrophy; vulvar atrophy; persistent itching
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Vulvar Diseases; Lichenoid Eruptions; Vulvar Lichen Sclerosus; Lichen Sclerosus et Atrophicus
• Other Study ID Numbers: DHF25211

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No