A Prospective Phase II Open-Label Pilot Study Evaluating the Efficacy and Safety of Methotrexate in the Treatment of Severe Vulvar Lichen Sclerosus
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
研究概览
简要总结
Vulvar lichen sclerosus is a chronic inflammatory skin disease affecting the vulva and genital region, which may cause intense pruritus, pain, burning sensations, and progressive scarring. In severe cases, the disease may lead to significant anatomical changes, sexual dysfunction, and a reduction in quality of life.
First-line treatment for vulvar lichen sclerosus consists of high-potency topical corticosteroids. Although many patients experience symptom relief, a considerable number of women continue to have persistent symptoms or progressive anatomical damage. For these patients, therapeutic options are limited.
MTX is an immunomodulatory medication that has been used for several decades in the treatment of inflammatory and autoimmune diseases. Previous clinical observations suggest that MTX may be beneficial for patients with severe or treatment-resistant vulvar lichen sclerosus; however, prospective clinical studies in this population remain scarce.
This prospective, open-label, phase II pilot study aims to evaluate the efficacy and safety of subcutaneous injectable MTX, administered once weekly at a standardized initial dose of 12.5 mg, in women with severe vulvar lichen sclerosus who have not responded adequately to standard topical therapy. Participants will receive treatment for 12 months, with regular clinical and laboratory monitoring.
The primary objective of the study is to assess whether treatment with MTX leads to improvement in symptoms and stabilization of vulvar skin changes, using patient-reported outcome measures and standardized clinical assessments. Secondary objectives include evaluation of treatment tolerability, adherence, and the occurrence of adverse events.
As a pilot study, this research is designed to generate preliminary data on feasibility, safety, and potential clinical benefit, which may guide future larger controlled studies and contribute to the development of evidence-based therapeutic strategies for women with severe vulvar lichen sclerosus.
详细描述
Vulvar lichen sclerosus is a chronic inflammatory dermatosis of the anogenital skin, characterized by epithelial thinning, dermal sclerosis, and progressive architectural distortion. In its severe form, the disease may present with persistent symptoms such as pruritus, pain, fissuring, and functional impairment, as well as irreversible vulvar anatomical changes.
Current standard management relies on the long-term use of high-potency topical corticosteroids. Although this approach is effective for many patients, a proportion of women with severe vulvar lichen sclerosus experience inadequate symptom control or continued progression of morphological changes.
For eligibility purposes, disease severity is defined according to the Vulvar Quality of Life Index (VQLI), a tool designed to measure the impact of vulvar disease on patients' quality of life. Clinical response over time will be assessed using the Clinical Scoring System for Vulvar Lichen Sclerosus. At present, evidence-based therapeutic guidance for severe vulvar lichen sclerosus remains limited.
Methotrexate (MTX) is an immunomodulatory agent with a long history of use in the treatment of inflammatory and autoimmune diseases. Its pharmacological properties, dosing strategies, and safety profile are well established in dermatology and rheumatology. Preliminary clinical observations suggest that MTX may offer benefit in selected patients with severe or treatment-refractory vulvar lichen sclerosus; however, prospective evaluations in this population remain scarce.
This study is designed as a prospective, open-label, phase II pilot clinical trial aimed at evaluating the feasibility, safety, and potential therapeutic effect of systemic MTX in women with severe vulvar lichen sclerosus refractory to standard topical therapy. The study adopts a single-arm design with longitudinal follow-up over a 12-month period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of genital lichen sclerosus et atrophicus (vulvar, perineal, or perianal);
- •Histopathological diagnosis of genital lichen sclerosus et atrophicus;
- •Disease severity defined according with a score above 24 on the Vulvar Quality of Life Index (VQLI);
- •Failure of symptom regression or progressive genital deformity after at least 3 months of treatment with a high-potency topical corticosteroid;
- •Normal baseline laboratory evaluation, including complete blood count, liver and kidney function tests, and negative serologies for HIV and hepatitis B and C;
- •For women of childbearing potential, a negative pregnancy test at screening.
排除标准
- •(assessed before signing the Informed Consent Form):
- •Lack of full mental or psychiatric capacity;
- •Need for assistance from a third party (legal guardian) to participate in the study;
- •Significant difficulty in understanding or expressing oneself in Portuguese;
- •Unavailability or inability to complete Likert-scale questionnaires;
- •Inability to comply with study requirements, including adherence to the treatment schedule and attendance at follow-up visits;
- •Unrealistic expectations regarding treatment benefits or the possibility of adverse effects;
- •Intention to become pregnant during the study period;
- •Refusal to adopt at least one adequate contraceptive method (hormonal or barrier) in women of childbearing potential;
- •Poor adherence to the commitment to abstain from alcoholic beverages;
- •Uncontrolled autoimmune comorbidities;
- •Refusal to sign the Informed Consent Form after adequate explanation and clarification of doubts;
- •Any indication of inability to comply with the conditions established in the research protocol. Decisions will be made to ensure participant safety and study integrity, with appropriate communication regarding the reasons for exclusion.
- •Exclusion Criteria (assessed after signing the Informed Consent Form):
- •Elevation of liver enzymes above normal limits or impaired renal function during laboratory monitoring. Exclusion refers to discontinuation of the experimental intervention; however, the participant will continue to receive comprehensive medical follow-up as needed;
- •Pregnancy. The participant will be withdrawn from the study intervention and referred for obstetric care, while continuing to receive medical follow-up;
- •Lack of cooperation, failure to attend scheduled follow-up visits, or failure to undergo required laboratory monitoring;
- •Any other condition that limits the participant's ability to comply with study procedures, as determined by the responsible investigator.
研究者
SAMIR ARBACHE
Principal Investigator
Clinica Dermatologica Arbache ltda