Clinical trial NCT02416531: Vulvar Lichen Sclerosus: Comparison Between Clobetasol Propionate, Photodynamic Therapy and Low-Intensity Laser
Official title: Vulvar Lichen Sclerosus: Therapeutic Comparison Between Clobetasol Propionate, Photodynamic Therapy and Low-Intensity Laser
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vulvar Lichen Sclerosus
Keywords: Vulvar lichen sclerosus
Photodynamic therapy
Low-level laser therapy
Clobetasol propionate
Lead sponsor: University of Nove de Julho
Sponsor class: OTHER
Collaborators: name: Hospital Perola Byington
First posted: 2015-04-15
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Vulvar lichen sclerosus (VLS) is a lymphocyte-mediated disease of unknown etiology that can cause intense itching as well stenosis, hindering the evacuation and urination. It can also limit the sex life due to severe local pruritus, pain and dyspareunia (pain during sexual intercourse). The standard treatment for this disease is the use of topical corticosteroids to reduce the clinical symptoms and to try to increase disease-free intervals. Photodynamic therapy (PDT), a treatment that associates a light radiation with a photosensitizing agent and low-level laser therapy (LLLT) are therapies that can promote effective immunomodulatory responses at the application site by means of photophysical and photochemical phenomena from the molecular to the systemic level, which promote their use in chronic dermatoses. The aim is to study and compare the effects of PDT, LLLT, and topical corticosteroid in VLS evaluating clinical, histological, immunohistochemical and spectroscopic responses. The study will be prospective, randomized, and controlled, in a population of 60 women with histological diagnoses of VLS, enrolled on the outpatient clinic of Genitoscopy Department of the Pérola Byington Hospital in São Paulo. There will be 3 treatments groups: PDT, LLLT and topical corticosteroid, where will be allocated by randomization 20 patients in each one. The clinical course will be monitored by measuring local temperature, itching, clamping (atrophy), and the appearance of the lesion. Histologically, the slides will be classified according to the Hewitt grading and will have the ordering of collagen fibers quantified. Immunohistochemical analysis will be done using the markers IFN-γ, TGF-β, CD4, CD8, IL-1, p53 and Ki-67. Finally, the spectroscopic evaluation will be done by reflectance. Descriptive and inferential statistical analyses will be conducted to compare the groups and for associations between different responses.

Detailed description: Dosimetry and Experimental Groups: There is no dosimetric protocol established for the treatment of VLS with PDT, nor with LLLT. According to the literature, energy densities range from 9 to 150 J/cm2 and power densities from 40 to 700 mW/cm2, not to mention work that do not report the dosimetry used. As such, the dosimetry to be used in this study is based on a pilot clinical study performed by our group.

The patients will be randomized into 3 groups with 20 patients in each one:

Group GC: Corticosteroid over the whole vulva. Clobetasol propionate 0.05% ointment applied once daily at a dose of 1 g/application (1 g sachets) for 4 weeks.

Group GPDT: Localized photodynamic therapy at 8 points of the vulva. Methylene blue 0.01% intralesional, λ = 660 ± 10 nm, P = 100 mW, PD = 510 mW/cm2, E = 4 J, ED = 20 J/cm2, t = 40 s, once a week for 4 weeks.

Group GLLLT: Localized low-level laser therapy at 8 points of the vulva. The same parameters as for GPDT, except for the methylene blue, once a week for 4 weeks.

Analyses: The histological and immunohistochemical analyses will be performed before and 30 days after the start of treatment, whereas clinical analysis will be performed weekly on treatment days for the GPDT and GLLLT groups. The control group will not be seen weekly because the standard treatment is performed by the patients themselves, in their own homes, for 30 days as recommended by the International Society for the Study of Vulvar Disease (ISSVD).

After treatments the patients will be followed for verification of recorrence during one year, at minimum.

Eligibility criteria: Inclusion Criteria:

* adult female patients (aged over 18 years);
* vulvar lichen sclerosus diagnosed histologically;
* normal level of cortisol confirmed by blood test.

Exclusion Criteria:

* adult female patients under the age of 18;
* patients with any kind of ongoing cancer and/or AIDS or coagulopathy, pregnant or breastfeeding women;
* patients using corticosteroids, immunosuppressants or anticoagulants;
* patients with renal, hepatic or pulmonary-cardiovascular failure;
* patients who have undergone any kind of organ transplantation in the last three years.

Primary outcomes:
measure: Change from baseline in biopsies at 1 month.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
Secondary outcomes:
measure: Count cells per mm2 by immunohistochemical reaction of IFN-γ, TGF-β, CD4, CD8, IL-1, p53 and Ki-67.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
measure: Percentage of relative reflectance as assessed by In-Vivo Reflectance Spectroscopy.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
measure: Temperature, as assessed by infrared thermographic camera, in Celsius degrees.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
measure: Itching, as assessed by Visual Analog Scale.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
measure: Clamping, as assessed by digital caliper, in mm.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
measure: Area, as assessed by digital camera, in cm2.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
measure: Collagen birefringence, as assessed by polarized light microscope, in nm.
timeFrame: Participants will be followed for 1 month during VLS's treatment.
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Hospital Pérola Byington
state: SP
Study officials:
affiliation: University of Nove de Julho
name: Daniela FT Silva, PhD
role: PRINCIPAL_INVESTIGATOR
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