Clinical trial NCT02573883
Conditions: Vulvar Lichen Sclerosus
Keywords: Vulva Lichen Sclerosus Fractionated Carbon Dioxide Laser Mona Lisa Laser Clobetasol Propionate Vulvodynia
Sponsor: Medstar Health Research Institute
Start date: 2015-10-01; Completion date: 2019-09-01
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

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.

Arms: arm 1: Patients with biopsy proven lichen sclerosus previously treated with clobetasol propionate arm 2: Patients with biopsy proven lichen sclerosus never previously treated with clobetasol propionate.
Interventions: intervention 1: Fractionated Carbon Dioxide Laser intervention 2: Clobetasol Propionate 0.05% ointment
Intervention descriptions: intervention 1: 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 2: 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.

Protocol documents:
Prot_SAP_000.pdf: 
Date: October 15, 2015 
NCT Number 02573883 
 
 
 
A randomized trial of Clobetasol Proprionate Versus Fractional CO2 
laser for the treatment of Lichen Sclerosus (CuRLS) 
 
 
 
PI: Cheryl Iglesia, MD 
 
 
Co-Investigators:  
 
Linda Scheider Burkett, MD 
Nemi Shah, BS 
Andrew I. Sokol, MD 
Robert E. Gutman, MD 
Amy J. Park, MD 
Tania M. Marek, NP 
Joanna L. Peterson, RN 
Mihirye Mete, PhD 
Alyson Davidson 
Moiuri Siddique 
 
 
 
 
 
Medstar Washington Hospital Center 
Georgetown University Hospital 
106 Irving Street NW, Suite 405S 
Washington DC, 20010 
 
 
 


 CuRLS Protocol  
 
 
2 
 
 
1.0 
PURPOSE and OBJECTIVES 
The purpose of this study is to compare the safety and efficacy of clobetasol proprionate .05% 
ointment to fractional CO2 laser procedure for the treatment of vulvar lichen sclerosus. 
 
Primary Outcome Measures: 
- 
The primary outcome will be the subjective and objective cure of vulvar symptoms of itching, burning, 
dyspareunia at 12 weeks post treatment, or 6 months [Time Frame:12 weeks ] using the SkINDEX-29 
and Vulvar Symptom Visual Analog Scale (VAS) 
Secondary Outcome Measures: 
- 
Complications [Time Frame: 6 week, 6 months, 1 year] pain, infection, de novo or worsening 
dyspareunia, contact dermatitis and burns 
- 
Subjective Vulvovaginal Symptoms Questionnaire (VSQ) 
- 
Objective Cure of Lichen Sclerosus [Time Frame:6 months, 1 year] using PHOTO documentation, Vulvar 
Signs Visual Analog Scale 
- 
Health Related Quality of Life (HRQOL) based on patient global impression of improvement and 
satisfaction as well as the Vaginal Health Index [Time Frame: 6 months, 1 year]  
 
2.0 
 
BACKGROUND and SIGNIFICANCE 
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. 1 
Clobetasol proprionate 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. Other therapeutic options include topical 
calcineurin inhibitors, surgery including incision and skin graft treatment, cryotherapy and phototherapy. Table 
1 summarizes current clinical comparative trials for lichen sclerosus involving topical steroid therapy. 
Clobetasol proprionate has a range of efficacy from 61-91% depending on the selected outcome criteria. 
Table 1. 
Author/year 
Study Design 
N 
Outcome 
Results 
Bracco, GL 
19932 
RCT 
Clobetasol vs. 
testosterone vs. 
progesterone 
vs. cream based 
therapy 
79 
-Subjective scaled symptom 
remission of vulval LS 
-Objective histologic and 
gross improvement 
-75% remission with  Temovate versus 
10% Progesterone,  
20%Testoterone, and   
10% cream based treatments had subjective 
remission of LS 
-Only Clobetasol  proprionate had significant  
histologic and gross improvement.  
Terra S, 
20143 
RCT  
clobetasol vs. 
phototherapy 
15 
-Mean relative reduction of 
total clinician’s score (TCS): 
subjective pruritus and 
burning/pain VAS, Skindex-2, 
20 MHz- ultrasonography, 
histopathological analysis 
35.6% decrease in mean (total clinical score) 
TCS in UV-A1 phototherapy group 
-51.4% decrease in mean TCS for clobetasol 
proprionate group; 
Skindex-29, pruritus, burning/pain significantly 
decreased 
-Phototherapy group’s only significant 
difference was with burning/pain 
-Significant difference in dermal density on 
ultrasound and histopathological reduction of 


 CuRLS Protocol  
 
 
3 
inflammatory infiltrate in clobetasol 
proprionate group and not Phototherapy 
group 
Lorenz B, 
19984 
Retrospective 
81 
-Subjective patient 
improvement of symptoms 
(pruritus, irritation, burning 
and dyspareunia) 
-Subjective clinician 
improvement of appearance 
-77% complete remission symptoms, 18% 
partial remission, and 5% no change after 
treatment with clobetasol proprionate 
-32% of patients had subjective complete 
remission of symptoms and 46% patients with 
subjective partial remission of symptoms 
Funaro D, 
20145 
RCT 
Clobetasol vs. 
tacrolimus 
55 
-Subject visual analog scale 
of symptoms (burning/pain, 
pruritus, and scaled 
improvement of condition) 
-Clinician cutaneous exam 
and photographs 
-Clobetasol proprionate had 66% efficacy of 
complete removal of subjective clinical signs 
compared to 14% in the tacrolimus group. 
-Objective clinical exam revealed clobetasol 
proprionate group had more significant 
decreases in vulvar skin papules and atrophic 
patches than tacrolimus group.  
Virgill A, 
20146 
RCT clobetasol 
vs. 
mometasone 
48 
-Subjective (visual analog 
scale and gynecologic 
subjective scale) 
-Objective (four point scale 
and gynecologic objective 
scale) scores improvement 
by 75% 
-59% of clobetasol group and 37% of 
mometasone furoate group had subjective 
score improvement. 
-67% of clobetasol and 48% of furoate group 
had objective score improvement 
Ayhan A, 
20077 
Retrospective 
140 
Subjective clinical response 
in six months 
91.7%  of clobestasol group and 77.5% of 
testosterone group reported subjective 
improvement  
 
The vulvovaginal SmartXide8 –V2-LR laser system by DEKA (Calezano, Italy) is a fractional 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. The SmartXide8–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. 
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 extracelluar matrix with collagen 
fibers.  
D-Pulse DOT therapy involves two types of energy: 
1) An initial high energy peak that allows laser energy removal of the superficial epithelial component 
2) A second variable lower peak power that enables the laser energy to penetrate into the submucosa 
stimulating new collagen synthesis 
The histopathologic changes associated with the CO2 laser treatment are supportive for reconstituting 
the vaginal epithelium back to physiologic function in patients with severe vaginal atrophy. The atrophic vaginal 
epithelium in GSM is thin with few cycles having glycogen storage rendering the vaginal pH less acidic and the 
epithelium completely atrophic. Two months after treatment, the epithelium is thickened with proliferating 
basal cells beneath. The structural integrity of the epithelium is enhanced with newly formed papillae and 
capillaries supporting the vaginal ecosystem. Epithelial cells have remarkably more glycogen forming the 
characteristic superficial, intermediate and deep layers. Fibroblasts undergo protein production to create the 
extracellular matrix including collagen.9 The mechanism by which the carbon dioxide laser is hypothesized to 
work is by thermal energy creating heat shock of proteins. As a result of the damage, cytokines and growth 
factors are released signally molecules to recruit fibroblasts and increase cell division.10 Table 2 includes prior 


 CuRLS Protocol  
 
 
4 
studies involving CO2 laser treatment for lichen sclerosus in both men and women. Studies are all retrospective 
and small in number with limited follow-up and only subjective outcome criteria. 
 
Table 2. Prior studies using Fractional C02 laser for lichen sclerosus  
Author and 
year 
Trial Design 
Primary Outcomes 
Findings 
Complications 
Peterson C, 
200411 
Case Report 
Subjective symptoms 
Visual re-epithelization 
All patients(N=2) with refractory 
anogenital lichen sclerosus had 
resolution of symptoms and re-
epithelization after 2-3 years 
with CO2 laser therapy 
None 
Kartamaa 
M, 199712 
Case Series 
Subjective assessment of 
lichen sclerosus (better, 
asymptomatic, some 
recurrence) 
Among male and female 
patients (N=10) with biopsy 
proven refractory LS, 76% were 
asymptomatic after CO2 laser 
treatment with mean follow up 
of 32 months. 
Three patients 
needed repeat 
treatment 
Windahl T, 
200613 
Retrospective 
cohort 
Subjective patient 
assessment of recurrence 
of symptoms, any visible 
penile lesion, recurrence of 
meatal stenosis 
In men with histologically 
verified penile lichen sclerosus 
treated with CO2 laser, 80% 
(N=50) had no local symptoms 
at mean follow up 14 years 
Two patients 
required further 
treatment 
Lee A, 
201514 
Case Series 
Subjective symptom 
resolution  
In women (N=5) with biopsy 
confirmed severe vulvar LS 
recalcitrant to topical 
corticosteroid treatment; four of 
whom responded positively to 
fractional CO2 laser treatment, 
and one to ablative CO2 laser 
therapy 
Two patients needed 
repeat treatment at 
6-8 months 
Two patients 
reported discomfort 
with laser treatment 
Ratz L, 
198415 
Case Report 
Subjective symptom 
resolution and re-
epithelization  
One case of balanitis xerotica 
obliterans refractory to topical 
treatments resolved after CO2 
laser treatment  
Syncopal episode 
after treatment 
 
Very little is known about long-term effects of CO2 fractional 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. SmartXide8 –V2-LR has some established outcome data for 
treatment of genitourinary syndrome of menopause GSM, also known as vulvovaginal atrophy. Table 3 List 
outcomes of the SmartXide8 –V2-LR system for treatment of vaginal atrophy.  
 
Table 3 Outcomes of SmartXide8 –V2-LR system for Vaginal Atrophy 
Author and 
year 
Trial Design 
N 
Primary Outcomes 
Findings 
Complications 
Salvatore 
R, 20148 
Prospective 
50 
Objective vulvovaginal 
atrophy  (VVA) symptoms-
Vaginal Health Score Index 
(VHIS) 
Subjective VVA symptoms – 
10 point visual analog scale 
Fractional CO2 laser improved VVA 
all subjective symptoms in women; 
significant objective improvement 
VHIS (13.1+/- 2.5 at baseline vs. 
23.1 +/- 1.9; p<0.001) 
None 


 CuRLS Protocol  
 
 
5 
(burning, vaginal itching, 
vaginal dryness, dyspareunia, 
and dysuria) 
SalvatoreR, 
2015 16 
Prospective 
77 
-Sexual function and quality of 
life (Female sexual function 
index and Short form 12) 
-Subjective symptoms (vaginal 
burning, dryness, dyspareunia, 
and dysuria with visual analog 
scale) 
-85% normal sexual life after CO2 
laser therapy in not sexually active 
group 
-Significant improvement in FSFI  
and VAS scores after treatment 
-Significant improvement in overall 
satisfaction with sexual life  after 
laser treatment 
None 
 
3.0 
 
STUDY DESIGN 
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. Patient will be randomized to 
monthly LASER treatment for 3 months or topical STEROID therapy (temovate propionate .05% ointment 
nightly for one month, three times weekly for 2 additional months, then as needed) in a 1:1 ratio using a 
computer generated randomization schedule. Grouping assignments will be kept in sealed consecutively 
numbered, opaque envelopes. Because of the nature of the treatment, it will not be possible to blind patients 
but the assessor will be blinded to the intervention. 
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 12 weeks after treatment is completed or 6 months from intake, and one year follow up. Subjective 
symptoms including vulvar itching, vulvar burning, vulvar irritation, pain with intercourse, tearing of the vulvar 
skin, painful urination, and painful defection will be rated with a validated visual analog scale (VAS), scaled 0-
10, see appendix 1. Higher values correspond to more bothersome symptoms.  The Skindex-29 questionnaire is 
a subjective measure of skin symptoms validated against the Medical Outcomes Study 36-item Short-Form 
Survey (SF-36)17, appendix 2. The Skindex-29 was developed in dermatology and modified for use in 
vulvadynia18.  The Skindex-29 is scored as a sum expressed on a 100-point scale with higher scores indicating 
lower quality of life. Validated quartiles are used to characterize disease symptoms, emotions, functioning, and 
overall score as either very little, mild, moderate, or severe19. Secondary outcomes of patient satisfaction and 
global impression of improvement will be collected using simple validated visual analog scale from 0-5, much 
worse to much better, appendix 4. A final subjective measure, the Vulvovaginal Symptoms Questionnaire 
(VSQ), a validated measure of vulvar symptoms, emotions, life impact, and sexual impact in postmenopausal 
women will be collected a secondary outcome20, appendix 5.  A higher total score on the VSQ corresponds to 
lower quality of life.  
Objective measures of the clinical appearance of vulvar lichen sclerosus will be completed by 
investigators at concurrent time points with the patient questionnaires. Non identifiable photo documentation 
of vulvar appearance will be completed using Fujifilm JX665 Digital Camera. Investigators blinded to treatment 
arm will complete visual assessment including white plaques/hypopigmentation, cigarette paper/thin skin, 
introital narrowing, perianal involvement (figure of eight shape), loss of labia minor, fusion of labia minora, 
philmosis of clitoral hood, vulvar fissure, and erosion scaled on validated visual analog scale, rated 0-10 from 
absent to severe, see appendix 1. Lower objective VAS scores corresponds to less severe Lichen Sclerosus 
disease. In addition, investigators will complete validated Vaginal Health Index (VHI) at all time points21, 
appendix 3. The VHI evaluates vulvovaginal overall elasticity, fluid secretion type and consistency, pH, epithelial 
mucosa, and moisture on a scale 1-5 from none to excellent. A lower VHI score corresponds to greater 
urogenital atrophy.  
The laser used in this clinical investigation complies with federal laser performance standards. 


 CuRLS Protocol  
 
 
6 
Fractional CO2 laser with 10600 um wavelength, 60 W pulse, continuous or pulsed with repetition rate, 
articulated arm with scanner hand-piece, 120 Vac power and 635 nm aiming beam. The laser power will be set 
at 26 W, dwell time of 800 microseconds, DOT spacing at 800 micro meters and normal scan mode. 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 or Medstar Lafayette Center, and include 3 sessions, 4 
weeks apart. A minimum of 2 weeks are required from the time of biopsy to treatment. Prior to treatment 
eutectic local anesthetic (EMLA) will be applied for at least 5 minutes up to 30 minutes and then wiped off prior 
to laser treatment. Photodocumentation will take place at baseline and at 6 months and one year following the 
last LASER or STEROID treatment. Interpretation of photodocumentation with clinical objective scale will be 
completed by blinded provider. 
 
4.0 
 
 SUBJECT POPULATION and SELECTION CRITERIA 
Patients presenting to urogynecology or gynecology clinic with vulvar symptoms and biopsy confirmed 
lichen sclerosus. 
 
Inclusion criteria: 
- 
Women  
- 
Biopsy proven symptomatic vulvar lichen sclerosus  
- 
Ability to understand the study, accept randomization and logistically follow-up with scheduled visits 
- 
Post-menopausal 
Exclusion criteria: 
- 
Known vulvar malignancy 
- 
Pregnancy or planning pregnancy or less than 3 months postpartum 
- 
Current or prior diagnosis of any gynecologic malignancy 
- 
Previous pelvic radiation therapy 
- 
Allergy to topical steroid 
- 
No active 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 vulvar hormonal or vulvar topical steroid use within 2 months of enrollment 
- 
History of vaginal mesh implant 
- 
IUD (Intrauterine Device) 
- 
Skindex-29 overall score <21, below mildly impaired health related quality of life threshold 
 
5.0 
 
SAMPLE SIZE CALCULATION 
The study will consist of 2 study groups (LASER vs STEROID therapy). We expect improved subjective 
and objective results in the LASER group at 3 months post treatment or 6 months from enrollment compared 
with the STEROID group.  
This study is designed as a two-group randomized clinical trial. 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)22 between the study groups with 24 
patients in each group, or 48 in total based on a one-sided two-sample t-test with alpha=0.05. By accounting for 
10% attrition, we propose to recruit 52 patients to the study to be randomized with a 1:1 ratio to each group, 
with a blocked component for those who used topical clobetasol in the past. The Skindex-29 has validated cutoff 
categories for mildly, moderately, and severely impaired health related quality of life scores, the mean difference 
between each quality of life measure overall score is between 6 and 7. Therefore, powering the study for a 
detection of mean difference of 16 points should measure significant quality of life improvement.23,24  


 CuRLS Protocol  
 
 
7 
 
 
 
 
 
Study Timeline: 
 
6.0 
 
DATA COLLECTION and TRANSMISSION  
The data will be collected from study participants at MedStar Washington Hospital Center or other 
Medstar Urogynecologic Clinic.  All data collection will be performed by research staff.  The baseline, 6 month, 
and 1 year visits will be in-person and include clinic evaluations. The 2 week and 2-month telephone call will be 
performed by the research coordinator.  At screening, each subject will be assigned a subject identification. 
Case report forms will be generated for each subject and completed by the investigator or study coordinator. 
Original case report forms will be securely maintained. 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. 
 
7.0 
 
HUMAN SUBJECT RESEARCH and ETHICAL CONCERNS 
Signed consent in English will be obtained from each participant / patient at the time of enrollment.  The 
objectives of the study and the data collection procedures will explained to every prospective participant 
before study enrollment.  An IRB-approved consent document will be used for protocols. Consent for the 
patients includes the right of the subject: 
- 
To either withdraw or refuse participation without prejudice at any time during the study; 
- 
To voluntarily participate in the research; 
 
Intake 
Visit 
Day 
0 
2 weeks 
4 weeks-14 weeks 
6 months 
1 year 
Vulvar biopsy (if never 
completed) 
X 
 
 
 
 
 
Vaginal STEROID or LASER 
 
 
STEROID daily x 4 
weeks 
LASER monthly x 
3 months 
STEROID three times 
weekly x 8 more weeks, 
then as needed 
LASER STOP at 12 weeks 
 
 
Vaginal Health Index scale 
(VHIS) 
 
X 
 
 
X 
x 
SkIndex-29 
Vulvar QoL Questionnaire 
Vulvovaginal Symptoms 
Questionnaire (VSQ) 
 
X 
 
 
X 
 
x 
Telephone call to check 
compliance and answer 
questions 
 
 
X 
X (8 weeks) 
 
 
Photodocumentation 
 
X 
 
 
X 
x 
Questionnaire of patient 
global impression of 
improvement and 
satisfaction 
PGI-I 
 
 
 
 
X 
x 


 CuRLS Protocol  
 
 
8 
- 
To receive new information about the study as it becomes available; 
- 
To understand the procedures, risks, and benefits; 
- 
To maintain confidentiality of personal medical information. 
 
8.0  
 
PROTECTION AGAINST RISK 
The proposed study involves changes in provision of program services to study participants. Description 
of random and blinded nature of the protocols will be explained by the physician in charge of the participant. 
To avoid or minimize potential risks, frequent monitoring for adverse events will be performed by study staff 
and the PI. 
Risks of clobetasol proprionate include skin irritation, burning, rash and change in skin pigmentation. 
 
Potential adverse reactions to laser use include ocular laser exposure which will be minimized with the 
use of protective eyewear with an optical density of 4x the treatment wavelength. Pain or mild to moderate 
discomfort, erythema, swelling, blistering, itching, numbness, change in pigmentation, scarring, and burns are 
other adverse events including as well as painful intercourse, change (postive or negative) in sexual response, 
including arousal around clitoris and orgasm. These risks will be minimized with laser use per manufacture 
instructions with trained personel and avoidance of laser treatment within 5mm of clitorial glans and hood.  All 
known risks will be disclosed to the participants via the informed consent process. All study participants will be 
closely monitored post treatment for adverse events. 
All known risks will be disclosed to the participants via the informed consent process. All study 
participants will be closely monitored post treatment for adverse events. All study investigators will receive 
extensive training on the study protocol. Attending staff/surgeons will also receive training on how to operate 
the laser and the appropriate settings for the vulvar treatment, supervised by the study mentor. Serious 
adverse events are defined as any untoward medical occurrence that (1) results in death, (2) is life-threatening, 
(3) requires inpatient hospitalization (4) results in persistent or significant disability or incapacity, (5) is a 
congenital anomaly/birth defect, or (6) is another medically important condition. 
Data safety and Monitoring Board (DSMB) headed by Dr. Stephanie Wethington, Director of 
Gynecologic Oncology at MedStar Washington Hospital Center, will review all serious adverse events, including 
any untoward occurrence that (1) results in death, (2) is life threatening, (3) requires inpatient hospitalization, 
(4) results in permanent or significant disability or incapacity, and (5) is another medically important condition. 
All ongoing data will be analyzed once half of patients have been recruited and at completion of recruitment 
and study conclusion. 
 
9.0 
 
SOURCES OF MATERIALS  
Medical record data and program records will be obtained for each participant.  Demographic 
information and personal history will be obtained by interview.  Study data, such as information obtained at 
follow-up assessment examination and interviews, will be obtained according to the time-frame specified in the 
protocol. 
 
10.0 
 
CONFIDENTIALITY 
This research staff will take every precaution to protect the confidentiality of the collected data.  All 
personnel with access to data collected have completed the Program for Ethics Education in Research training 
with the appropriate HIPAA certification. Completed data forms will be placed in locked file cabinets, and only 
authorized staff members will have access to the data.  The data will be compiled into a computerized database 
and will be stored on computers used exclusively for research studies and are safeguarded by passwords 
known only to authorized personnel. Photo documentation is to capture isolated vulvar and perineal area. 
Other identifiable body parts including patient’s face will not be included in photographs. Photographs used as 


 CuRLS Protocol  
 
 
9 
part of photo documentation will be uploaded from digital camera after each encounter. The photograph file 
will be labeled with non identifiable patient number. Digital camera photo card will be cleared and photographs 
stored on research computers safeguarded by passwords. Fujifilm JX665 Digital Camera will be stored with 
storage card in locked file cabinets, and only authorized staff members will have access. Data are analyzed 
collectively.  No personal identities are revealed to the statistician.  The data used are obtained strictly for the 
purposes of the research in question.  Any printout information and photographs will be destroyed once the 
project is completed and reports written. 
 
11.0 
 
TIMING OF STUDY and RECRUITMENT  
 
The study investigators plan to start recruitment in August 2015.  Study recruitment is expected to be 
complete within 5 years by August 2018.  One year follow-up will be complete by August 2019.  This study will 
be complete and the results analyzed by the primary investigator, Dr. Cheryl Iglesia.  
 
12.0 
 
STATISTICAL ANALYSIS 
Statistical intention-to-treat and per protocol analysis will be completed in R (version 3.4, Vienna, 
Austria 2017) with demographic and questionnaire scores reported as means and standard deviations or 
medians and interquartile ranges. Chi square or Fisher’s exact, two-sample t-test and Mann Whitney U will be 
used to compare categorical, continuous, and non-parametric variables, respectively. D-Agostino test will be 
used to assess normality. Two-way ANOVA analysis of mean Skindex-29 score improvement based on prior 
steroid exposure and treatment group will be performed.  
 
13.0 
 
REFERENCES  
 
1. 
Chi C-C, Kirtschig G Baldo M et al. Topical interventions for genital lichen sclerosus. Cochrane Database 
of Systematic Reviews 2011; Issue 12. Art No.: CD008240. DOI: 10.1002/14651858. CD008240. Pub2 
2. 
Bracco GL, Carli P, Sonni L, Maestrini G, et al .  Clinical and histologic effects of 
topical treatments of vulval lichen sclerosus. A critical evaluation. J Reprod Med. 1993 Jan; 38 (1): 37-
40.  
3. 
Terra S, Gambichler T, Rose K, et al. UV-A1 Phototherapy vs. Clobetasol Propionate, 0.05% in Treatment 
of Vulvar Lichen Sclerosus. Dermatol. 2014; 150(6):621-627.  
4. 
Lorenz B, Kaufman RH, Kutzner SK. Lichen sclerosus. Therapy with clobetasol propionate. J Reprod 
Med. 1998 Sep; 43(9):790-4.  
5. 
Funaro D, Lovett A, Leroux N, et al. A double-blind, randomized prospective study evaluating topical 
clobetasol propionate 0.05% versus topical tacrolimus 0.1% in patients with vulvar lichen sclerosus. J 
Am Acad Dermatol. 2014 Jul; 71(1): 84-91. 
6. 
Virgill A, Borghi A, Toni G, et al. First randomized trial on clobetasol propionate and mometasone 
furoate in the treatment of vulvar lichen sclerosus: results of efficacy and tolerability. Br J 
Dermatol. 2014 Aug;171(2):388-96.  
7. 
Ayhan A, Guven S, Guvendaq Guven ES, et al. Topical testosterone versus clobetasol for vulvar lichen 
sclerosus. Int J Gynaecol Obstet. 2007 Feb; 96(2): 117-21 
8. 
 Salvatore R, Nappi E, Zerbinati N et al. A 12-week treatment with fractional C02 laser for vulvovaginal 
atrophy: a pilot study. Climacteric 2014; 17: 1 
9. 
Zerbinati N, Origoni M, Candiani M, et al. Microscopic and ultrastructural modifications of 
postmenopausal atrophic vaginal mucosa after fraction carbon dioxide treatment. Lasers Med Sci 
(2015) 30:429-436. 
10. 
Salvatore S, Maggiore U, Athanasiou S, et al. Histological study of the effects microablative fractional 
carbon dioxide laser on atrophic vaginal tissue: an ex vivo study. Menopause. 2015 Jan 20. 22:000-009. 


 CuRLS Protocol  
 
 
10 
11. 
Peterson C, Lane J, Ratz J. Successful Carbon Dioxide Laser Therapy for Refractory Anogenital Lichen 
Sclerosus. Dermatol Surg 2004; 30:1148- 1151.  
12. 
Kartamaa M, Reitamo S. Treatment of lichen sclerosus with carbon dioxide laser vaporization. Br J 
Dermatol. 1997 Mar; 136(3):356-9.  
13. 
Windahl T. Is Carbon dioxide laser treatment of lichen sclerosus effective in the long run? Scand J Urol 
Nephrol. 2006; 40(3):208-11.  
14. 
 Lee A, Lim A, Fischer G. Fractional carbon dioxide laser in recalcitrant vulval lichen sclerosus. 2015 Mar 
5. Doi 10.1111/ajd.12305 [Epub ahead of print] 
15. 
Ratz L. Carbon dioxide laser treatment of balanitis xerotica obliterans. J. Am. Acad. Dermatol 1984; 
10:925-8.  
16. 
Salvatore R, Parma M, Chionna F, et al. Sexual function after fractional microablation CO2 laser in 
women with vulvaginal atrophy. Climacteric. 2015 Apr; 18(2):219-25.  
17. 
Chren MM, Lasek RJ, Quinn LM, Covinsky KE. Convergent and discriminant validity of a generic and a 
disease-specific instrument to measure quality of life in patients with skin disease. J Invest Dermatol. 
1997 Jan;108(1):103-7 
18. 
Ponte M, Klemperer E, Sahay A, et al. Effects of vulvodynia on quality of life. J Am Acad Dermatol. 2009 
Jan;60(1):70-6. 
19. 
Prinsen CA, Lindeboom R, de Korte J. Interpretation of Skindex-29 Scores: Response to Sampogna and 
Abeni. Journal of Investigative Dermatology (2012) 132, 1500–1501. 
20. 
Erekson EA, Yip SO, Wedderburn TS, et al. The Vulvovaginal symptoms in postmenopausal women. 
Menopause. 2013 Sep;20(9):973-9.  
21. 
Vaginal health index: Bachmann, G. Urogenital ageing: an old problem newly 
recognized.Maturitas, 1995 Sept;22: S1-S5. 
22. 
He Z, Lu C, Chren MM, et al. Development and psychometric validation of the Chinese version of 
Skindex-29 and Skindex-16. Health Qual Life Outcomes. 2014 Dec 24;12:190. 
23. 
El Fakir S, Baybay H, Bendahhou K, et al. Validation of the Skindex-16 questionnaire in patients with 
skin diseases in Morocco. J Dermatolog Treat. 2014 Apr;25(2):106-9.  
24. 
Prinsen CA, Lindeboom R, de Korte J. Interpretation of Skindex-29 scores: cutoffs for mild, moderate, 
and severe impairment of health-related quality of life. Journal of Investigative Dermatology (2011) 
131, 1945–1947.  
 
Appendix 1: 
 
 Subjective Symptoms VISUAL ANALOG SCALE (VAS) 
 
Not bothersome 
 
 
 
 
 
 
Most Bothersome 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
SYMPTOMS 
Vulvar itching 
Vulvar burning 
Vulvar irritation 
Pain with intercourse 
Tearing of vulvar skin 
Painful urination 
Painful defection 
 
 


 CuRLS Protocol  
 
 
11 
 
Objective Signs VISUAL ANALOG SCALE (VAS) 
 
Absent  
 
Mild 
 
 
Moderate 
 
 
Severe 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
SIGNS 
White plaques/hypopigmentation 
Cigarette paper, thin skin 
Introital narrowing 
Perianal involvement (figure of 8 shape) 
Loss of labia minora 
Fusion of labia minora 
Phimosis of clitoral hood 
Vulvar fissure 
Erosion 
Appendix 2:  SKINDEX 
These questions concern your feelings over the past 4 weeks about the skin condition that has  
bothered you the most. Check the answer that comes closest to the way you have been feeling. 
 
HOW OFTEN DURING THE PAST FOUR WEEKS  
DO THESE STATEMENTS DESCRIBE YOU? 
___________________________________________ 
NEVER         RARELY      SOMETIMES       OFTEN      ALL THE TIME   
___________________________________________ 
 
  1. My skin hurts    .    .    .   .    .    .   .    .    .   .    .    .   .    .    .    . 
 
   o1              o2              o3               o4              o5 
 
  2. My skin condition affects how well I sleep    .    .    .    .    .    . 
 
   o1              o2              o3               o4              o5 
 
  3. I worry that my skin condition may be serious    .    .    .    .    . 
 
   o1              o2              o3               o4              o5 
 
  4. My skin condition makes it hard to work or do hobbies    .    . 
 
   o1              o2              o3               o4              o5 
 
  5. My skin condition affects my social life   .    .    .    .    .    .    . 
 
   o1              o2              o3               o4              o5 
 
  6. My skin condition makes me feel depressed    .    .    .    .    .   
 
   o1              o2              o3               o4              o5 
 
  7. My skin condition burns or stings    .    .    .    .    .    .    .     . 
 
   o1              o2              o3               o4              o5 
 
  8. I tend to stay at home because of my skin condition    .    .    . 
 
   o1              o2              o3               o4              o5 
 
  9. I worry about getting scars from my skin condition    .    .    .   
 
   o1              o2              o3               o4              o5 
 
10. My skin itches    .    .    .    .    .    .    .    .    .    .    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
11. My skin condition affects how close I can be with those I love. 
 
   o1              o2              o3               o4              o5 
 
12. I am ashamed of my skin condition    .    .    .    .    .    .    .    . 
 
   o1              o2              o3               o4              o5 
 
13. I worry that my skin condition may get worse    .    .    .    .    . 
 
   o1              o2              o3               o4              o5 
 
14. I tend to do things by myself because of my skin condition    . 
 
   o1              o2              o3               o4              o5 
 
15. I am angry about my skin condition    .    .    .    .    .    .    .    . 
 
   o1              o2              o3               o4              o5 
 
16. Water bothers my skin condition (bathing, washing hands)    . 
 
   o1              o2              o3               o4              o5 


 CuRLS Protocol  
 
 
12 
 
 
 
 
 
 
 
Please turn to next page 
 
These questions concern your feelings over the past 4 week about the skin condition that has  
bothered you the most. Check the answer that comes closest to the way you have been feeling. 
 
 
HOW OFTEN DURING THE PAST 4 WEEK  
DO THESE STATEMENTS DESCRIBE YOU? 
_____________________________________________ 
 
NEVER         RARELY      SOMETIMES       OFTEN         ALL THE  
                                                                                             TIME 
_____________________________________________ 
 
21. I am embarrassed by my skin condition    .    .    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
22. My skin condition is a problem for the people I love    .     
 
   o1              o2              o3               o4              o5 
 
23. I am frustrated by my skin condition    .    .    .    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
24. My skin is sensitive    .    .    .    .    .    .    .    .    .    .    .    .    .   
 
   o1              o2              o3               o4              o5 
 
25. My skin condition affects my desire to be with people     
 
   o1              o2              o3               o4              o5 
 
26. I am humiliated by my skin condition    .    .    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
27. My skin condition bleeds    .    .    .    .    .    .    .    .    .    .    .    
 
   o1              o2              o3               o4              o5 
 
28. I am annoyed by my skin condition    .    .    .    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
29. My skin condition interferes with my sex life    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
30. My skin condition makes me tired    .    .    .    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
 
Chren MM, Lasek RJ, Quinn LM, Covinsky KE. Convergent and discriminant validity of a generic and a disease-
specific instrument to measure quality of life in patients with skin disease. J Invest Dermatol. 1997 
Jan;108(1):103-7 
 
 
17. My skin condition makes showing affection difficult    .    .    . 
 
   o1              o2              o3               o4              o5 
 
18. I worry about side-effects from skin medications / treatments. 
 
   o1              o2              o3               o4              o5 
 
19. My skin is irritated    .    .    .    .    .    .    .    .    .    .    .    .    .     
 
   o1              o2              o3               o4              o5 
 
20. My skin condition affects my interactions with others    .    .     
 
   o1              o2              o3               o4              o5 


 CuRLS Protocol  
 
 
13 
Appendix 3: Vaginal Health Index 
 
 
Overall elasticity* 
Fluid secretion type  
& consistency 
pH 
Epithelial mucosa 
Moisture 
1 
None 
None 
6.1 
Petechiae noted  
before contact 
None, mucosa 
inflamed 
2 
Poor 
Scant, thin yellow 
5.6 – 6.0 
Bleeds with light contact 
None, mucosa 
not inflamed 
3 
Fair 
Superficial, thin white 
5.1 – 5.5 
Bleeds with scraping 
Minimal 
4 
Good 
Moderate, thin white 
4.7 – 5.0 
Not friable, thin mucosa 
Moderate 
5 
Excellent 
Normal                
(white flocculent) 
 ≤ 4.6 
Not friable, normal 
mucosa 
Normal 
*Lower score corresponds to greater urogenital atrophy  
 
                                                                                                                                                                                                                   
 
 


 CuRLS Protocol  
 
 
14 
Appendix 4 
 
Patient Global Impression of Improvement 
 
Circle how you feel your symptoms are after treatment: 
 
Much Worse 
 
Worse  
Same 
 
Better  
Much Better 
     1 
 
 
  2 
 
   3 
 
   4  
 
         5 
 
 
 
Level of satisfaction after treatment 
 
How would you define the level of satisfaction with the treatment? 
 
Very Dissatisfied 
Dissatisfied 
 
Same 
 
Satisfied 
Very Satisfied 
 
1 
 
 
2 
 
   3 
 
     4 
 
 
5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 CuRLS Protocol  
 
 
15 
Appendix 5 
 
The Vulvovaginal Symptom Questionnaire 
The following questions were developed to assess skin symptoms of women. The skin surrounding the 
vagina is called the vulva. Just like skin in other parts of the body, the vulva can sometimes become 
irritated. Many women experience discomfort in the region of the vulva. These symptoms may be mild, 
but can sometimes be severe. The following questions will ask you about your vulvar skin symptoms 
during the past week. 
During the past week, have you been bothered by: 
1. 
Your vulva itching? 
0□ No 
1□ Yes 
2. 
Your vulva burning or stinging? 
0□ No 
1□ Yes 
3. 
Your vulva hurting? 
0□ No 
1□ Yes 
4. 
Your vulva being irritated? 
0□ No 
1□ Yes 
5. 
Your vulva being dry? 
0□ No 
1□ Yes 
6. 
Discharge from your vulva or vagina? 
0□ No 
1□ Yes 
7. 
Odor from your vulva or vagina? 
0□ No 
1□ Yes 
8. 
Worry about your vulvar symptoms? 
(for example, that it will spread, get worse, scar, etc.) 
 
0□ No 
 
1□ Yes 
9. 
The appearance of your vulva? 
0□ No 
1□ Yes 
10. 
Frustration about your vulvar symptoms? 
0□ No 
1□ Yes 
11. 
Embarrassment about your vulvar symptoms? 
0□ No 
1□ Yes 
12. 
The effects of your vulvar symptoms on your interactions with 
others? 
0□ No 
1□ Yes 
13. 
The effects of your vulvar symptoms on your desire to be with 
people? 
0□ No 
1□ Yes 
14. 
Your vulvar symptoms making it hard to show affection? 
0□ No 
1□ Yes 
15. 
The effects of your vulvar symptoms on your daily activities? 
0□ No 
1□ Yes 
16. 
Your vulvar symptoms affecting your desire to be intimate? 
0□ No 
1□ Yes 
17. 
Are you currently sexually active with a partner? 
 
 
 
□ No→ Thank you. You are done with this questionnaire. 
 
 
 
□ Yes→ Please proceed with the next 4 questions 
 
 
18. 
The effects of your vulvar symptoms on your sexual relationships? 
0□ No 
1□ Yes 
19. 
Your vulvar symptoms causing pain during sexual activity? 
0□ No 
1□ Yes 
20. 
Your vulvar symptoms causing dryness during sexual activity? 
0□ No 
1□ Yes 
21. 
Your vulvar symptoms causing bleeding during sexual activity? 
0□ No 
1□ Yes 
 
 

ICF_001.pdf: 
 
Office of Research Integrity 
6525 Belcrest Rd, Suite 700 
Hyattsville, MD 20782 
 
Approval Notice 
 Response to Tabled 
 
04-Apr-2018  
 
 
MedStar Washington Hospital Center 
106 Irving Street, NW, Suite 2100 North 
Washington, DC 20010 
 
Protocol Number: 2016-144 
PI Name:  
Cheryl Iglesia MD 
Protocol Title:  
A Randomized Extension Trial Comparing Clobetasol Prioprionate Versus 
Radiofrequency CO2 Laser for the Treatment of Lichen Sclerosus (eCuRLS) 
 
 
Dear Cheryl Iglesia MD, 
 
The Response to Tabled - (Continuation) submission was reviewed by IRB # 1 Washington in 
accordance with full board review procedures on 13-Mar-2018.  
 
The IRB has approved the submission. You can begin research activities. The approval is valid from 
13-Mar-2018 through 12-Mar-2019. Any modifications to the IRB-approved protocol and other 
supporting documents must be reviewed and approved by the IRB prior to implementation.  
 
 
If the study will continue beyond 12-Mar-2019, please submit a continuation request form forty-five (45) 
days prior to 12-Mar-2019 to allow the IRB sufficient time to review and approve the request. 
If you have any questions, please contact me at 301-560-2979. 
 
Thank you, 
 
Ashlee Tidwell 
Office of Research Integrity 
 
Enclosure: IRB Stamped Informed Consent  
 


IRB number: 
2016-144 
Clinical Site IC Version: 
19Sept2016 
Project Title: 
A crossover trial comparing £Iobetasol Proprionate Versys Fractional C02 laser for the 
treatment of.bichen 
(eCuRLS) 
Principal Investigator: 
Cheryl Iglesia 
lVIedStar 
Washington 
Hospital 
Institution: 
Center, MedStar Health 
MedStar Health Research Institute Informed Consent for Clinical Research 
INTRODUCTION 
We invite you to take part in A crossov!r trial comparing Clobetasol Proprionate Versys fractional 
C02 laser for the treatment of .bichen §.clerosus (eCuRLS) research study called eCuRLs. You were 
selected as a possible participant in this study because you have lichen sclerosus. Please take your 
time to read this form, ask any questions you may have and make your decision. We encourage you to 
discuss your decision with your family, friends and your doctor(s). 
WHAT IS THE PURPOSE OF THIS STUDY? 
Lichen sclerorus has been traditionally treated with steroid creams such as clobetasol. However, we would like 
to see if laser treatment can also impact lichen sclerosus and how it compares to steroid cream. This study is 
being .done to compare the effects, good and bad, of fractional C02 laser treatment or clobetasol 
proprionate .05% ointment on you and your lichen sclerosus to see which is better. 
WHAT ELSE SHOULD I KNOW ABOUT THIS RESEARCH STUDY? 
It is important that you read and understand several points that apply to all who take part in our studies: 
•  
Taking part in the study is entirely voluntary and refusal to partiCipate will not affect any rights or 
benefits you normally have; 
•  
You mayor may not benefit from taking part in the study, but knowledge may be gained from your 
participation that may help others; and 
•  
You may stop being in the study at any time without any penalty or losing any of the benefits you would 
have normally received. 
The nature of the study, the benefits, risks, discomforts and other information about the study are discussed 
further below. If any new information is learned, at any time during the research, which might affect your 
participation in the study, we will tell you. We urge you to ask any questions you have about this study with the 
staff members who explain it to you and with your own advisors prior to agreeing to participate. 
WHO IS IN CHARGE OF THIS STUDY? 
MedStar Health 
Research Institute 
Consent To Participate In A 
MedStar Health Research 
Institute 
Clinical Research Study 
IRB Approval Stamp 
(ORA USE ONLY - DO NOT CHANGE ANY INFORMATION IN THIS SECTION) 
Page 1 of8 
Participant Initials ___ 
Fonn Revision Date: 1212015 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED 


IRB number: 
2016-144 
Clinical Site IC Version: 
19Sept2016 
A crossover trial comparing !!Ioi?etasol Proprionate Versys Fractional C02 laser for the 
Project Title: 
treatment of!:ichen §clerosus (eCuRLS) 
MedStar 
Washington 
Hospital 
Principal Investigator: 
Cheryl Iglesia 
Institution: 
Center, MedStar Health 
The investigator is Dr. Cheryl Iglesia. The research is being sponsored by Foundation for Female Health 
Awareness (FFHA) and MedStar Washington Hospital Center Graduate Medical Education Grant (GME). 
MedStar Health Research Institute is being paid by FHFA and GME to conduct this study with Dr. Cheryl 
Iglesia as the primary investigator. 
WHO CANNOT PARTICIPATE IN THIS STUDY? 
You cannot be in this study if any of the following apply to you: 
• 
Male 
• 
Non-English speaking 
• 
Known vulvar cancer 
• 
Pregnancy or planning pregnancy or less than 3 months postpartum 
• 
Current or prior diagnosis of any gynecologic cancer 
• 
Previous pelvic radiation therapy 
• 
Allergy to topical steroid 
• 
Active urinary tract infection, or other vulvar infection 
• 
Pelvic organ prolapse outside the vagina 
• 
Treatment with oral steroids or other medications affecting the immune system 
• 
Treatment with vaginal hormonal or vulvar topical steroid use within the past 2 months 
• 
An IUD or intrauterine device 
WHAT IF I AM PRESENTLY PARTICIPATING IN ANOTHER RESEARCH STUDY? 
Are you presently participating in any other research studies? 
Yes 0 
NoD 
If yes, please state which study(ies) ___________________ 
While participating in this study, you should not take part in any other research project without approval 
from the people in charge of each study. This is to protect you from possible injury arising from such 
things as extra blood drawing, extra x-rays, interaction of research drugs, or similar hazards. 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY? 
About (54) people will take part in this study, worldwide. (54) people will be recruited at this site. 
WHAT HAPPENS IF I AGREE TO BE IN THE STUDY? 
If you agree to take part in this study, you will be receive either Fractional C02 laser treatment or clobetasol 
proprionate 0.05%. If you have already received the laser treatment, you will now receive clobetasol 
;;=C£;:. l 
MedStar Health 
Consent To Participate In A 
IRB Approval Stamp 
(ORA USE ONLY· DO NOT CHANGE ANY INFORMATION IN THIS SECTION)
Research Institute 
MedStar Health Research  
Institute  
Clinical Research Study  
Page 2 of8 
Fonn Revision Date: 1212015
Participant Initials ___ 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED 


IRB number: 
2016-144  
Clinical Site IC Version: 
19Sept2016 
A crossover trial comparing 9,lobetasol Proprionate Versys Fractional C02 laser for the 
Project Title: 
treatment of .bichen §clerosus (eCuRLS) 
MedStar 
Washington 
Hospital 
Principal Investigator: 
Cheryl Iglesia 
Institution: 
Center, MedStar Health 
proprionate 0.05% steroid treatment. If you have already received clobetasol proprionate 0.05% steroid 
treatment, you will now receive laser treatment. 
You will be asked to fill out questionnaires again. A photo of disease on the vulva will be taken 
again. The LASER treatment is monthly for 3 months. The topical STEROID therapy, clobetasol 
propionate .05% ointment is nightly for one month then three times weekly for 2 additional months. At the 
end of the 6 months, treatment you will be asked to complete follow up questionnaires and another 
photograph of disease on your vulva will be taken for comparison. 
The procedures/treatments in this study that are considered experimental/investigational are: use of the 
Mona Lisa Fractional C02 laser for vulvar lichen sclerosus. 
For procedures/treatments that are not experimental/investigational, 
•  The following procedures are part of the research study and would not normally be done as part of 
your routine care: photo documentation. questionnaires 
•  
The following procedures would normally be done as part of your routine care whether or not you are 
enrolled in the study: vulvar biopsy, use of clobetasol propionate .05% ointment. 
HOW LONG WILL I BE IN THE STUDY? 
We think you will be in the study for 6 months. 
The investigator may decide to take you off this study if it is believed to be in your best interest, you fail to 
follow instructions, new information becomes known about the safety of the study, or for other reasons the 
investigator or sponsor believes are important. 
You can stop participating at any time. However, if you decide to stop partiCipating in the study, we encourage 
you to talk to the investigator and your regular doctor first so they can help you decide what other options may 
be best for your medical care once you are off study. 
If you suddenly withdraw from the study. we may not be able to use any of the information gathered from your 
participation. 
WHAT ARE THE RISKS AND SIDE EFFECTS OF THIS STUDY? 
If you decide to participate in this study, you should know there may be risks. You should discuss these with 
the investigator and/or your reg'ular doctor and you are encouraged to speak with your family and friends about 
any potential risks before making a decision. Potential risks and side effects related to this study include: 
MedStar Health 
Research Institute 
Consent To Participate In A 
MedStar Health Research 
Institute 
Clinical Research Study 
Page 3 of8 
PartiCipant Initials ___ 
IRB Approval Stamp 
(ORA USE ONLY - DO NOT CHANGE ANY INFORMATION IN THIS SECTION) 
FORn Revision Date: 1212015 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED 


I 
IRS number: 
2016-144 
Clinical Site IC Version: 19Sept2016 
Project Title: 
A crossover trial comparing !!Iobetasol Proprionate Versys Fractional C02 laser for the 
treatment of!:ichen §clerosus (eCuRLS) 
Principal Investigator: 
Cheryl Iglesia 
MedStar 
Washington 
Hospital 
Institution: 
Center, MedStar Health 
Risks of clobetasol proprionate include skin irritation, burning, rash and change in skin pigmentation. Potential 
adverse reactions to laser use include ocular laser exposure which will be minimized with the use of protective 
eyewear with an optical density of 4x the treatment wavelength. Risk to the patient include pain or mild to 
moderate discomfort, erythema, swelling, blistering, itching, numbness, change in pigmentation, sacarring and 
bums as well painful intercourse. These risks will be minimized with laser use per manufacture instructions 
with trained personel. All known risks will be disclosed to the participants via the informed consent process. All 
study participants will be closely monitored post treatment for adverse events. 
Risks and side effects that may occur include: 
• 
Pain and irritation at treatment site 
• 
Bleeding from biopsy site 
• 
Infection at treatment site 
Risks and side effects that are less likelv to occurinclude: 
• 
Swelling 
• 
Blistering 
• 
Itching 
• 
Numbness 
• 
Painful intercourse 
• 
Scarring 
• 
Laser eye injury 
Risks and side effects that rarelv occurinclude: 
• 
Change in pigmentation 
• 
Laser burns 
• 
Change in sexual response, affecting arousal around clitoris and orgasm 
Please tell the investigator about all medications including over-the-counter drugs or herbal supplements you 
are taking, even if you don't think they are important. 
. 
Only you can take the study drug. Do not share it with anyone else. It must be kept out of reach of 
children and persons who may not be able to read or understand the label. 
There may also be risks and side effects other than those listed above that we cannot predict. Many side 
effects go away in a short time after the steroid or laser treamentis stopped, but, in some cases, side effects 
can be serious, long lasting and/or life threatening. If you have any unwanted side effects, you should ask the 
MedStar Health 
Consent To PartiCipate In A 
Research Institute 
MedStar Health Research 
Institute 
Clinical Research Study 
Page40f8 
Participant Initials ___ 
IRB Approval Stamp 
(ORA USE ONLY - DO NOT CHANGE ANY INFORMATION IN THIS SECTION) 
Fo"" Revision Date: 1212015 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED 


IRB number: 
2016-144 
Clinical Site IC Version: 19Sept2016 
Project Title: 
A crossover trial comparing Qlobetasol Proprionate Versys Fractional C02 laser for the 
treatment of,bichen §clerosus (eCuRLS) 
Principal Investigator: 
Cheryl Iglesia 
MedStar 
Washington 
Hospital 
Institution: 
Center, MedStar Health 
investigator whether there are any medications or other things that may be done to make the side effect less 
uncomfortable. 
For more information about risks and side effects, please ask Dr. Cheryl Iglesia. 
ARE THERE ANY BENEFITS TO TAKING PART IN THE STUDY? 
You mayor may not get any direct benefit from being in this study. We cannot promise that you will 
experience any benefits from participating in this study. We hope the information learned from this study will 
benefit others in the future. 
WHAT OTHER OPTIONS ARE THERE? 
Instead of being in this study, you have these options: 
• 
You always have the option to not be in this study or to refuse any medical treatment. 
WHAT ABOUT CONFIDENTIALITY? 
Your personal health information (PHI) will be kept private to the extent allowed by law. Study records 
identifying you will be kept confidential and will not be made publicly available. You will not be identified by 
name in any publications resulting from this study. You will be asked to sign a separate form that will give 
permiSSion to the investigator, representatives from government agencies, including the Food and Drug 
Administration (FDA), institutional review boards, the sponsor and/or the sponsor's representative(s), and 
certain other people, agencies or entities, to look at and review the records related to this study including your 
personal health information and the information discovered during this study. This separate form explains in 
greater detail who will have access to your records, what type of information will be reviewed and for what 
purposes, how long your permission for others to review and release your records will last, and how you may 
withdraW your permission if necessary. If you do not wish to sign this permission form you will not be allowed 
to participate in this study. 
Information, that does not include personally identi'fiable information, concerning this clinical trial has been or 
may be submitted, at the appropriate and required time, to the government-operated clinical trial registry data 
bank, which contains registration, results, and other information about registered clinical trials. This data bank 
can be accessed by you and the general public at www.ClinicaITrials.gov. Federal law requires clinical trial 
information for certain clinical trials to be submitted to the data bank. 
A Data Safety and MonitOring Board, which is a group of experts not connected to the study, will be reviewing 
the data from this research throughout the study. We will tell you about the new information from this or other 
studies that may affect your health, welfare, or willingness to stay in this study. 
MedStar Health 
Research Institute 
Consent To Participate In A 
MedStar Health Research 
Institute 
Clinical Research Study 
Page 5 of8 
Participant Initials ___ 
IRB Approval Stamp 
(ORA USE ONLY· DO NOT CHANGE ANY INFORMA11ON IN THIS SECTION) 
Form Revision Date: 1212015 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED 


IRB number: 
2016-144 
Clinical Site IC Version: 19Sept2016 
A crossover trial comparing 
Proprionate Versys Fractional C02 laser for the 
Project Title: 
treatment of ,bichen §clerosus (eCuRLS) 
Principal Investigator: 
Cheryl Iglesia 
MedStar 
Washington 
Hospital 
Institution: 
Center, MedStar Health 
WILL I BE PAID FOR PARTICIPATING IN THIS STUDY? 
You will not be paid for being in this study. Materials and information obtained from you in this research may 
be used for commercial or non-commercial purposes. It is the policy of MedStar Health Research Institute, 
MedStar Health, Inc. and its affiliated entities not to provide financial compensation to you should this occur. 
WHAT ARE THE COSTS? 
You do not have to pay anything to be in this study. However, if taking part in this study leads to procedures or 
care not included in the study, it may lead to added costs for you or your insurance company. You will not be 
charged for appropriate tests, procedures, medications, etc. that are part of this research study. 
However, you, or your insurance company, will be charged for any other portion of your care that is considered 
standard of care. You may be responsible for any co-payments and deductibles that are standard for your 
insurance coverage during each office visit. This may include: cost for steroid cream, baseline vulvar biopsy, 
and follow up study visits to monitor treatment. 
WHAT IF I'M INJURED OR BECOME ILL DURING THE STUDY? 
We will make every effort to prevent injuries or illness from occurring while you are in the study. In the case of 
an injury, illness, or other harm occurring to you during, or resulting from, the study, you should seek medical 
treatment. You should also contact the study doctor as soon as possible. You or your insurance company will 
be charged for any continuing medical care and/or hospitalization that are not a part of the study. 
If you suffer an injury related to the study drug or study procedures, the reasonable costs of necessary medical 
treatment of the injury will not be reimbursed by the Foundation for Female Health Awareness to the extent 
these costs are not covered by your insurance or other third party coverage. 
No funds have been set aside, by the MedStar Health Research Institute, MedStar Health, or its affiliated 
entities to repay you in case of injury, illness, or other harm occurring during, or resulting from the study, and 
their current policies do not provide for payments for lost wages, cost of pain and suffering, or additional 
expenses. By agreeing to this you do not give up your rights to seek compensation in the courts. 
WHAT ARE MY RIGHTS AS A PARTICIPANT? 
•  You have the right to be told about the nature and purpose of the study; 
•  You have the right to be given an explanation of the exactly what will be done in the study and given a 
deSCription of potential risks, discomforts, or benefits that can reasonably be expected; 
MedStar Health 
Research Institute 
Consent To Participate In A 
MedStar Health Research 
Institute 
Clinical Research Study 
IRB Approval Stamp 
(ORA USE ONLY· DO NOT CHANGE ANY INFORMATION IN THIS SECTION) 
Page 6 of8 
Participant Initials ___ 
Fonn Revision Date: 1212015 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED 


IRB number: 
2016-144  
Clinical Site IC Version: 19Sept2016 
A crossover trial comparing globetasol Proprionate Versys Fractional C02 laser for the 
Project Title: 
treatment of,bichen §clerosus (eCuRLS) 
MedStar 
Washington 
Hospital 
Principal Investigator: 
Cheryl Iglesia 
Institution: 
Center, MedStar Health 
•  You have the right to be informed of any appropriate alternatives to the study, including, if appropriate, any 
drugs or devices that might help you, along with their potential risks, discomforts and benefits; 
•  You have the right to ask any questions you may have about the study; 
•  You have the right to decide whether or not to be in the study without anyone misleading or deceiving you;
and 
. 
•  You have the right to receive a copy of this consent form. 
By signing this form, you will not give up any legal rights you may have as a research participant. You may 
choose not to take part in or leave the study at any time. If you choose to not take part in or to leave the study, 
your regular care will not be affected and you will not lose any of the benefits you would have received 
normally. We will tell you about new information that may affect your health, welfare, or willingness to be in 
this study. 
WHO DO I CALL IF I HAVE QUESTIONS OR PROBLEMS? 
For questions about the study or a research-related injury, contact the investigator, Joanna Peterson, clinical 
research nurse coordinator, at (202)-877-0526. If you are having a medical emergency, you should call 911 or 
go directly to the nearest emergency room. 
For questions about your rights as a research participant, contact the MedStar Health Research Institute. 
Direct your questions to the Office of Research Integrity at: 
Address:  MedStar Health Research 
Telephone: 
(301) 560-2912  
Institute  
6525 Belcrest Rd. 
Toll Free: 
(800) 793-7175  
Suite 700 
Fax 
(301) 560-7336  
Hyattsville. MD 20782  
MedStar Health 
Consent To Participate In A 
Research Institute 
MedStar Health Research 
Institute 
Clinical Research Study 
Page 7 of8 
Participant Initials ___ 
IRB Approval Stamp 
(ORA USE ONLY· DO NOT CHANGE ANY INFORMA110N IN THIS SEC110N) 
Form Revision Date: 1212015 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED 


IRS number: 
2016-144 
Clinical Site IC Version: 
19Sept2016 
A crossover trial comparing £Iobetasol Proprionate Versys Fractional C02 laser for the 
Project Title: 
treatment of ,bichen §clerosus (eCuRLS) 
Principal Investigator: 
Cheryl Iglesia 
MedStar 
Washington 
Hospital 
Institution: 
Center, MedStar Health 
SIGNATURES 
As a representative of this study, I have explained the purpose, the procedures, the possible benefits and risks 
that are involved in this research study. Any questions that have been raised have been answered to the 
individual's satisfaction. 
Signature of Person Obtaining Consent 
Date of Signature 
Printed Name of Individual Obtaining Consent: _______________ 
I, the undersigned have been informed about this study's purpose, procedures, possible benefits and risks, 
and I have received a copy of this consent. I have been given the opportunity to ask questions before I sign, 
and I have been told that I can ask other questions at any time. I voluntarily agree to be in this study. I am 
free to stop being in the study at any time without need to justify my decision and if I stop being in the study I 
understand it will not in any way affect my future treatment or medical management. I agree to cooperate with 
Dr. Cheryl Iglesia and the research staff and to tell them immediately if I experience any unexpected or 
unusual symptoms. 
Participants signature 
Date of Signature 
Printed Name of Participant 
As the Principal Investigator (or his designee) for this research study, I attest that the participant has voluntarily 
agreed to be part of this study, the risks and benefits of the study have been fully explained, and any questions 
have been addressed to the participant's satisfaction. 
Principal Investigator's Signature 
Date of Signature 
;;-= 
MedStar Research 
Institute 
Consent To Participate In A 
MedStar Health Research 
Institute 
Clinical Research Study 
Page 8 of8 
IRB Approval Stamp 
(ORA USE ONLY· DO NOT CHANGE ANY INFORMATION IN THIS SECTION) 
Fonn Revision Date: 07/25/2010 
 
IRB Approval Stamp 
MedStar Health Research Institute 
 
APPROVAL DATE 03/13/2018 
APPROVAL EXPIRES 03/12/2019 
 
IRB APPROVED