- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02416531
Vulvar Lichen Sclerosus: Comparison Between Clobetasol Propionate, Photodynamic Therapy and Low-Intensity Laser (VLSCBCPPTLIL)
Vulvar Lichen Sclerosus: Therapeutic Comparison Between Clobetasol Propionate, Photodynamic Therapy and Low-Intensity Laser
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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SP
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São Paulo, SP, Brazil, 01314000
- Hospital Perola Byington
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Corticosteroid
Clobetasol propionate 0.05% ointment applied once daily at a dose of 1 g/application (1 g sachets) for 4 weeks.
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Clobetasol propionate 0.05% ointment applied once daily at a dose of 1 g/application (1 g sachets) for 4 weeks.
Other Names:
|
Experimental: Photodynamic therapy
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.
|
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
Other Names:
|
Experimental: Low level laser therapy
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.
|
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from baseline in biopsies at 1 month.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
|
Biopsies will be performed at two points: at baseline to confirm the VLS and subsequent inclusion in the research protocol, and at the end of 30 days to investigate the prognosis after treatment.
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Participants will be followed for 1 month during VLS's treatment.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Count cells per mm2 by immunohistochemical reaction of IFN-γ, TGF-β, CD4, CD8, IL-1, p53 and Ki-67.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
|
Once deparaffinized, the tissue samples will be subjected to antigen retrieval, endogenous enzyme blocking, background blocking, incubations of antibodies, and counter-staining according to the instructions of the manufacturers.
The cells that are positively stained by the immunohistochemical reaction will be counted with the aid of ImageJ software (National Institutes of Health, Maryland, USA) by two independent pathologists without prior knowledge of the experimental groups.
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Participants will be followed for 1 month during VLS's treatment.
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Percentage of relative reflectance as assessed by In-Vivo Reflectance Spectroscopy.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
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A portable spectrophotometer (400-900 nm) comprising a light source and a fiber-optic probe will be used directly on the surface of the vulvar skin in areas affected by VLS and in healthy areas of the same patients.
Relative spectra will be obtained for the wavelengths corresponding to those of the therapeutic window, and the percentage of relative reflectance will be calculated.
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Participants will be followed for 1 month during VLS's treatment.
|
Temperature, as assessed by infrared thermographic camera, in Celsius degrees.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
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Measurements will be recorded as images in all sessions before, during, and after irradiation to observe the thermal fluctuation in the procedures.
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Participants will be followed for 1 month during VLS's treatment.
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Itching, as assessed by Visual Analog Scale.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
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In each session, the patients will be asked about the intensity of vulvar itching to assess its severity and duration, before and after irradiation, according to a visual analog scale.
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Participants will be followed for 1 month during VLS's treatment.
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Clamping, as assessed by digital caliper, in mm.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
|
The clamping of the lesion to monitor skin atrophy will be done before irradiation at each session, using a digital caliper, transversely and longitudinally in relation to the labia majora.
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Participants will be followed for 1 month during VLS's treatment.
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Area, as assessed by digital camera, in cm2.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
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The appearance and area of the lesion will be monitored with a digital camera at every session, before irradiation.
To facilitate measurements, a metric scale will be rested on all vulvas for the photos.
The areas of the lesions will be quantified using ImageJ software (National Institutes of Health, Maryland, USA).
|
Participants will be followed for 1 month during VLS's treatment.
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Collagen birefringence, as assessed by polarized light microscope, in nm.
Time Frame: Participants will be followed for 1 month during VLS's treatment.
|
The correlation between birefringence and collagen ordering has been used since the 1960s.
To the present date, polarized-light microscopy is an efficient method to quantify the change in collagen birefringence due to the effects of different agents.
Since atrophy of the skin is a characteristic symptom of patients with VLS, the more detailed study of collagen fibers will elucidate the interaction of radiation with this type of tissue.
|
Participants will be followed for 1 month during VLS's treatment.
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Daniela FT Silva, PhD, University of Nove de Julho
Publications and helpful links
General Publications
- Murphy R. Lichen sclerosus. Dermatol Clin. 2010 Oct;28(4):707-15. doi: 10.1016/j.det.2010.07.006.
- Kreuter A, Wischnewski J, Terras S, Altmeyer P, Stucker M, Gambichler T. Coexistence of lichen sclerosus and morphea: a retrospective analysis of 472 patients with localized scleroderma from a German tertiary referral center. J Am Acad Dermatol. 2012 Dec;67(6):1157-62. doi: 10.1016/j.jaad.2012.04.003. Epub 2012 Apr 24.
- Oyama N, Chan I, Neill SM, Hamada T, South AP, Wessagowit V, Wojnarowska F, D'Cruz D, Hughes GJ, Black MM, McGrath JA. Autoantibodies to extracellular matrix protein 1 in lichen sclerosus. Lancet. 2003 Jul 12;362(9378):118-23. doi: 10.1016/S0140-6736(03)13863-9.
- Gambichler T, Kammann S, Tigges C, Kobus S, Skrygan M, Meier JJ, Kohler CU, Scola N, Stucker M, Bechara FG, Altmeyer P, Kreuter A. Cell cycle regulation and proliferation in lichen sclerosus. Regul Pept. 2011 Apr 11;167(2-3):209-14. doi: 10.1016/j.regpep.2011.02.003. Epub 2011 Feb 15.
- Terlou A, Santegoets LA, van der Meijden WI, Heijmans-Antonissen C, Swagemakers SM, van der Spek PJ, Ewing PC, van Beurden M, Helmerhorst TJ, Blok LJ. An autoimmune phenotype in vulvar lichen sclerosus and lichen planus: a Th1 response and high levels of microRNA-155. J Invest Dermatol. 2012 Mar;132(3 Pt 1):658-66. doi: 10.1038/jid.2011.369. Epub 2011 Nov 24.
- Gambichler T, Terras S, Kreuter A, Skrygan M. Altered global methylation and hydroxymethylation status in vulvar lichen sclerosus: further support for epigenetic mechanisms. Br J Dermatol. 2014 Mar;170(3):687-93. doi: 10.1111/bjd.12702.
- Perez-Lopez FR, Ceausu I, Depypere H, Erel CT, Lambrinoudaki I, Rees M, Schenck-Gustafsson K, Tremollieres F, van der Schouw YT, Simoncini T; EMAS, Spanish Menopause society. EMAS clinical guide: vulvar lichen sclerosus in peri and postmenopausal women. Maturitas. 2013 Mar;74(3):279-82. doi: 10.1016/j.maturitas.2012.12.006. Epub 2013 Jan 3.
- Selim MA, Hoang MP. A histologic review of vulvar inflammatory dermatoses and intraepithelial neoplasm. Dermatol Clin. 2010 Oct;28(4):649-67. doi: 10.1016/j.det.2010.07.005. Epub 2010 Aug 30.
- Monsalvez V, Rivera R, Vanaclocha F. [Lichen sclerosus]. Actas Dermosifiliogr. 2010 Jan-Feb;101(1):31-8. Spanish.
- Brodrick B, Belkin ZR, Goldstein AT. Influence of treatments on prognosis for vulvar lichen sclerosus: facts and controversies. Clin Dermatol. 2013 Nov-Dec;31(6):780-6. doi: 10.1016/j.clindermatol.2013.05.017.
- Hantschmann P, Sterzer S, Jeschke U, Friese K. P53 expression in vulvar carcinoma, vulvar intraepithelial neoplasia, squamous cell hyperplasia and lichen sclerosus. Anticancer Res. 2005 May-Jun;25(3A):1739-45.
- Thorstensen KA, Birenbaum DL. Recognition and management of vulvar dermatologic conditions: lichen sclerosus, lichen planus, and lichen simplex chronicus. J Midwifery Womens Health. 2012 May-Jun;57(3):260-75. doi: 10.1111/j.1542-2011.2012.00175.x.
- Lipkin D, Kwon Y. Therapies and nursing care of women with vulvar dermatologic disorders. J Obstet Gynecol Neonatal Nurs. 2014 Mar-Apr;43(2):246-52. doi: 10.1111/1552-6909.12286. Epub 2014 Feb 6.
- Burrows LJ, Creasey A, Goldstein AT. The treatment of vulvar lichen sclerosus and female sexual dysfunction. J Sex Med. 2011 Jan;8(1):219-22. doi: 10.1111/j.1743-6109.2010.02077.x. Epub 2010 Oct 18.
- Terras S, Gambichler T, Moritz RK, Stucker M, Kreuter A. UV-A1 phototherapy vs clobetasol propionate, 0.05%, in the treatment of vulvar lichen sclerosus: a randomized clinical trial. JAMA Dermatol. 2014 Jun;150(6):621-7. doi: 10.1001/jamadermatol.2013.7733.
- Olejek A, Steplewska K, Gabriel A, Kozak-Darmas I, Jarek A, Kellas-Sleczka S, Bydlinski F, Sieron-Stoltny K, Horak S, Chelmicki A, Sieron A. Efficacy of photodynamic therapy in vulvar lichen sclerosus treatment based on immunohistochemical analysis of CD34, CD44, myelin basic protein, and Ki67 antibodies. Int J Gynecol Cancer. 2010 Jul;20(5):879-87. doi: 10.1111/IGC.0b013e3181d94f05.
- Osiecka BJ, Nockowski P, Jurczyszyn K, Ziolkowski P. Photodynamic therapy of vulvar lichen sclerosus et atrophicus in a woman with hypothyreosis--case report. Photodiagnosis Photodyn Ther. 2012 Jun;9(2):186-8. doi: 10.1016/j.pdpdt.2012.02.002. Epub 2012 Mar 27.
- Romero A, Hernandez-Nunez A, Cordoba-Guijarro S, Arias-Palomo D, Borbujo-Martinez J. Treatment of recalcitrant erosive vulvar lichen sclerosus with photodynamic therapy. J Am Acad Dermatol. 2007 Aug;57(2 Suppl):S46-7. doi: 10.1016/j.jaad.2006.04.005. No abstract available.
- Hillemanns P, Untch M, Prove F, Baumgartner R, Hillemanns M, Korell M. Photodynamic therapy of vulvar lichen sclerosus with 5-aminolevulinic acid. Obstet Gynecol. 1999 Jan;93(1):71-4. doi: 10.1016/s0029-7844(98)00321-4.
- Sotiriou E, Panagiotidou D, Ioannidis D. An open trial of 5-aminolevulinic acid photodynamic therapy for vulvar lichen sclerosus. Eur J Obstet Gynecol Reprod Biol. 2008 Dec;141(2):187-8. doi: 10.1016/j.ejogrb.2008.07.027. Epub 2008 Sep 7. No abstract available.
- Biniszkiewicz T, Olejek A, Kozak-Darmas I, Sieron A. Therapeutic effects of 5-ALA-induced photodynamic therapy in vulvar lichen sclerosus. Photodiagnosis Photodyn Ther. 2005 Jun;2(2):157-60. doi: 10.1016/S1572-1000(05)00062-1. Epub 2005 Aug 3.
- Belotto RA, Chavantes MC, Tardivo JP, Euzebio Dos Santos R, Fernandes RCM, Horliana ACRT, Pavani C, Teixeira da Silva DF. Therapeutic comparison between treatments for Vulvar Lichen Sclerosus: study protocol of a randomized prospective and controlled trial. BMC Womens Health. 2017 Aug 10;17(1):61. doi: 10.1186/s12905-017-0414-y.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Lichen-768168
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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