Vulvar Lichen Sclerosus
Conditions
Keywords
vulvar dystrophy, vulvar atrophy, persistent itching, leukoplakia, hyperkeratosis, sexual function
Brief summary
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.
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.
Interventions
DEVICEThe 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).
Sponsors
Candela Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single Group Assignment
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators | At Baseline, 3, 6 and 12 months after the final treatment | 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. |
| 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 | Baseline, 3 , 6 and 12 months after the final treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Sexual Function on the Female Sexual Function Index (FSFI) at 3 Months and 6 Months After the Final Treatment | Baseline and 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. |
| Subject Satisfaction At the 12-Month Follow-up | 12 months after the final treatment | 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. |
| Treatment Associated Pain Score | Immediately after the 1st, 2nd, 3rd, 4th and 5th monthly treatments post baseline | 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. |
Countries
United States
Participant flow
Pre-assignment details
Although 14 subjects enrolled, 1 subject was withdrawn from the study due to a protocol violation and 1 subject was found to be not eligible prior to her first treatment. Therefore, 12 subjects are included in this analysis.
Participants by arm
| Arm | Count |
|---|---|
| CO2RE® Treatment All eligible subjects that underwent up to 5 treatments at 4±1-week intervals to the vulva with a fractional CO2 laser and maintained the protocol regimen.
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 treatment of leukoplakia (vulvar dystrophies). | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | CO2RE® Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 56.6 Years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| FSFI | 13.9 score on a scale STANDARD_DEVIATION 10.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline, 3 , 6 and 12 months after the final treatment
Population: At Baseline, 12 patients had 55 architectural changes present (score \>0). One subject missed the 12-month follow-up, one subject missed the 3- and 12-month follow-ups and one subject missed the 6-month follow-up. Hence, at the 3- and 6-month follow-ups, 11 subjects were assessed (with 51 architectural changes averaged for each visit) and at the 12-month follow-up 10 subjects were assessed (with 49 architectural changes averaged).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CO2RE® 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 | Average score of architectural changes at Baseline | 2.18 score on a scale | Standard Deviation 0.72 |
| CO2RE® 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 | Average score of architectural changes at 3-month follow-up | 1.10 score on a scale | Standard Deviation 0.9 |
| CO2RE® 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 | Average score of architectural changes at 6-month follow-up | 1.04 score on a scale | Standard Deviation 0.87 |
| CO2RE® 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 | Average score of architectural changes at 12-month follow-up | 1.08 score on a scale | Standard Deviation 0.91 |
Primary
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.
Time frame: At Baseline, 3, 6 and 12 months after the final treatment
Population: At Baseline, 12 subjects had 96 clinical signs present (score \>0). One subject missed the 12-month follow-up, one subject missed the 3- and 12-month follow-ups and one subject missed the 6-month follow-up. Hence, at 3- and 6-month follow-up visits 11 subjects were assessed (with 89 clinical signs averaged for each visit) and at the 12-month follow-up visit 10 subjects were assessed (with 79 clinical signs averaged).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CO2RE® Treatment | Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators | Average score of clinical signs at Baseline | 1.85 score on a scale | Standard Deviation 0.73 |
| CO2RE® Treatment | Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators | Average score of clinical signs at 3-months follow-up visit | 0.65 score on a scale | Standard Deviation 0.74 |
| CO2RE® Treatment | Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators | Average score of clinical signs at 6-months follow-up visit | 0.65 score on a scale | Standard Deviation 0.76 |
| CO2RE® Treatment | Average Scores for VLS Clinical Signs Present At Baseline, 3, 6 and 12 Months After the Last Treatment as Assessed by the Investigators | Average score of clinical signs at 12-months follow-up visits | 0.73 score on a scale | Standard Deviation 0.83 |
Secondary
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.
Time frame: Baseline and 3 months and 6 months after the final treatment
Population: At Baseline, 12 patients completed FSFI questionnaires. At the 3-month visit, 11 subjects completed the FSFI (one subject missed the visit). At the 6-month follow-up, 12 subjects completed the FSFI (one subject missed her visit but provided her self-assessments remotely).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CO2RE® Treatment | Change From Baseline in Sexual Function on the Female Sexual Function Index (FSFI) at 3 Months and 6 Months After the Final Treatment | Mean Change in FSFI At the 3-Month Follow-up | 4.06 units on a scale | Standard Error 2.25 |
| CO2RE® Treatment | Change From Baseline in Sexual Function on the Female Sexual Function Index (FSFI) at 3 Months and 6 Months After the Final Treatment | Mean Change in FSFI At the 6-Month Follow-up | 4.53 units on a scale | Standard Error 2.41 |
Secondary
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.
Time frame: 12 months after the final treatment
Population: Two subjects missed the 12-month follow-up. Therefore, subject assessments were reported for 10 subjects at the 12-month follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CO2RE® Treatment | Subject Satisfaction At the 12-Month Follow-up | 8 Participants |
Secondary
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.
Time frame: Immediately after the 1st, 2nd, 3rd, 4th and 5th monthly treatments post baseline
Population: A total of 57 sessions were conducted (10 subjects had 5 treatments,1 subject had 4 treatments and 1 subject had 3 treatments)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CO2RE® Treatment | Treatment Associated Pain Score | 2.6 score on a scale | Standard Deviation 2.5 |