Vulvar Lichen Sclerosus: Comparison Between Clobetasol Propionate, Photodynamic Therapy and Low-Intensity Laser

Condition(s) targeted: Vulvar Lichen Sclerosus

Intervention: Clobetasol propionate (Drug); Photodynamic therapy (Radiation); Low level laser therapy (Radiation)

Phase: N/A

Status: Recruiting

Sponsored by: Daniela de Fátima Teixeira da Silva

Official(s) and/or principal investigator(s):
Daniela FT Silva, PhD, Principal Investigator, Affiliation: University of Nove de Julho

Overall contact:
Renata A Belotto, Phone: 55 11 968419306, Email: rebelotto@terra.com.br

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.

Official title: Vulvar Lichen Sclerosus: Therapeutic Comparison Between Clobetasol Propionate, Photodynamic Therapy and Low-Intensity Laser

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change from baseline in biopsies at 1 month.

Secondary outcome:

Count cells per mm2 by immunohistochemical reaction of IFN-γ, TGF-β, CD4, CD8, IL-1, p53 and Ki-67.

Percentage of relative reflectance as assessed by In-Vivo Reflectance Spectroscopy.

Temperature, as assessed by infrared thermographic camera, in Celsius degrees.

Itching, as assessed by Visual Analog Scale.

Clamping, as assessed by digital caliper, in mm.

Area, as assessed by digital camera, in cm2.

Collagen birefringence, as assessed by polarized light microscope, in nm.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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.

Renata A Belotto, Phone: 55 11 968419306, Email: rebelotto@terra.com.br

Hospital Pérola Byington, São Paulo, SP 01314000, Brazil; Recruiting
Renata A Belotto, Phone: 55 11 968419306, Email: rebelotto@terra.com.br

Related publications:

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Starting date: January 2015
Last updated: April 9, 2015