Methotrexate for Severe Vulvar Lichen Sclerosus

NCT07352917 | Recruiting Phase 2

• 1 other identifier: 005
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Vulvar Lichen Sclerosus

Keywords

Vulvar lichen sclerosus; Quality of life; methotrexate

Outcome Measures

Primary Outcomes (1)

• Change in vulvar symptom severity

  Change in vulvar symptom severity from baseline to 12 months, assessed using the total symptom score of the Clinical Scoring System for Vulvar Lichen Sclerosus (symptom domains only), as described by Günthert et al. (J Sex Med. 2012;9:2342-2350). The total score ranges from 0 to 30 points and is calculated by summing the items within the symptom domain, yielding a single aggregated value per assessment. Higher scores indicate greater symptom severity. Symptoms related to sexual discomfort or pain during sexual activity are not included in the primary outcome score and will be recorded separately and reported descriptively.

  12 months

Secondary Outcomes (3)

• Change in vulvar morphology

  12 months

• Change in vulvar-related quality of life

  12 months

• Safety and tolerability of methotrexate

  12 months

Study Arms (1)

Subcutaneous Methotrexate

EXPERIMENTAL

Participants allocated to this single study arm will receive subcutaneous injectable methotrexate, administered once weekly at a standardized initial dose of 12.5 mg. Dose adjustments may be made according to clinical response and safety monitoring, based on predefined protocol criteria. Folic acid supplementation will be administered on the day following the weekly methotrexate injection. Participants will be followed quarterly for a 12-month period. Subjective clinical efficacy outcomes will be assessed, along with objective analyses related to genital morphology, documented through standardized photographic records, as well as treatment safety outcomes, including clinical and laboratory assessments performed every three months.

Drug: Methotrexate (MTX)

Interventions

Methotrexate (MTX) DRUG

Subcutaneous injectable methotrexate administered once weekly, starting at a standardized initial dose of 12.5 mg per administration. Dose adjustments may be performed according to clinical response and safety monitoring, based on predefined protocol criteria. Folic acid supplementation will be administered on the day following the weekly methotrexate injection.

Subcutaneous Methotrexate

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Clinica Dermatologica Arbache ltda: lead

Study Sites (1)

DermoCentro

São José dos Campos, São Paulo, 12245760, Brazil

RECRUITING

Related Publications (13)

• Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharm Stat. 2005;4:287-291.

  BACKGROUND

• Jasionowska S, Almadori A, Goble M, Langridge BJ, Iakovou D, Kamel F, McKenzie M, Mclean A, Boyle D, Zenner N, Swale V, Butler PEM. A systematic review of outcome measures evaluating treatment efficacy in vulval lichen sclerosus and evaluation of patients' priorities. Skin Health Dis. 2024 Jul 5;4(5):e422. doi: 10.1002/ski2.422. eCollection 2024 Oct.

  PMID: 39355724 BACKGROUND

• Saunderson RB, Harris V, Yeh R, Mallitt KA, Fischer G. Vulvar quality of life index (VQLI) - A simple tool to measure quality of life in patients with vulvar disease. Australas J Dermatol. 2020 May;61(2):152-157. doi: 10.1111/ajd.13235. Epub 2020 Jan 27.

  PMID: 31984477 BACKGROUND

• Gunthert AR, Duclos K, Jahns BG, Krause E, Amann E, Limacher A, Mueller MD, Juni P. Clinical scoring system for vulvar lichen sclerosus. J Sex Med. 2012 Sep;9(9):2342-50. doi: 10.1111/j.1743-6109.2012.02814.x. Epub 2012 Jul 3.

  PMID: 22759453 BACKGROUND

• Ghafari-Saravi A, Foster E. Treatment of Refractory Vulvar Lichen Sclerosus With Methotrexate. J Low Genit Tract Dis. 2024 Apr 1;28(2):202-204. doi: 10.1097/LGT.0000000000000795. Epub 2024 Jan 10.

  PMID: 38518219 BACKGROUND

• Cuellar-Barboza A, Bashyam AM, Ghamrawi RI, Aickara D, Feldman SR, Pichardo RO. Methotrexate for the treatment of recalcitrant genital and extragenital lichen sclerosus: A retrospective series. Dermatol Ther. 2020 Jul;33(4):e13473. doi: 10.1111/dth.13473. Epub 2020 Jun 23. No abstract available.

  PMID: 32347617 BACKGROUND

• Urun M, Gursel Urun Y, Sarikaya Solak S. A case of extragenital linear lichen sclerosus along the lines of Blaschko responding to methotrexate. Acta Dermatovenerol Alp Pannonica Adriat. 2020 Sep;29(3):149-151.

  PMID: 32975302 BACKGROUND

• Kreuter A, Tigges C, Gaifullina R, Kirschke J, Altmeyer P, Gambichler T. Pulsed high-dose corticosteroids combined with low-dose methotrexate treatment in patients with refractory generalized extragenital lichen sclerosus. Arch Dermatol. 2009 Nov;145(11):1303-8. doi: 10.1001/archdermatol.2009.235.

  PMID: 19917961 BACKGROUND

• Nayeemuddin F, Yates VM. Lichen sclerosus et atrophicus responding to methotrexate. Clin Exp Dermatol. 2008 Aug;33(5):651-2. doi: 10.1111/j.1365-2230.2008.02721.x. Epub 2008 May 27. No abstract available.

  PMID: 18507666 BACKGROUND

• Warren RB, Weatherhead SC, Smith CH, Exton LS, Mohd Mustapa MF, Kirby B, Yesudian PD. British Association of Dermatologists' guidelines for the safe and effective prescribing of methotrexate for skin disease 2016. Br J Dermatol. 2016 Jul;175(1):23-44. doi: 10.1111/bjd.14816. No abstract available.

  PMID: 27484275 BACKGROUND

• Nguyen BT, Kraus CN. Vulvar Lichen Sclerosus: What's New? Cutis. 2024 Mar;113(3):104-106. doi: 10.12788/cutis.0967. No abstract available.

  PMID: 38648581 BACKGROUND

• Hargis A, Ngo M, Kraus CN, Mauskar M. Systemic Therapy for Lichen Sclerosus: A Systematic Review. J Low Genit Tract Dis. 2024 Jan 1;28(1):84-90. doi: 10.1097/LGT.0000000000000775. Epub 2023 Nov 4.

  PMID: 37924260 BACKGROUND

• Singh N, Mishra N, Ghatage P. Treatment Options in Vulvar Lichen Sclerosus: A Scoping Review. Cureus. 2021 Feb 24;13(2):e13527. doi: 10.7759/cureus.13527.

  PMID: 33786234 BACKGROUND

MeSH Terms

Conditions

Vulvar Lichen Sclerosus

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Vulvar Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

SAMIR ARBACHE, PHD

CONTACT

+55 12 981221011; samir.arbache@gmail.com

SAMIA ARBACHE, MD

CONTACT

+55 11 96498-1831; samiaarbache@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study is designed as a single-center, prospective, open-label, phase II pilot interventional trial with a single-group assignment. All enrolled participants will receive the same intervention, consisting of weekly subcutaneous methotrexate administration, and will be followed longitudinally for clinical and safety outcomes over a 12-month period. There will be no randomization, masking, or control group, consistent with the exploratory and feasibility-oriented nature of a pilot study.

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: January 20, 2026
• Study Start: January 21, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

BR (1)