Topical Methotrexate vs Minoxidil for Localized Alopecia Areata (MTX-MNX-AA)

Comparative Study Between Topical Methotrexate 1% Gel and Minoxidil 5% Spray in the Treatment of Localized Alopecia Areata: A Randomized Controlled Trial

Alopecia areata is an autoimmune disorder characterized by well-defined, non-scarring patches of hair loss on the scalp and other hair-bearing areas. Although several treatment options are available, there is no universally accepted standard therapy, and treatment responses vary widely among patients.

Minoxidil is commonly used for hair regrowth due to its ability to stimulate hair follicles and prolong the anagen phase of the hair cycle. Methotrexate, an immunosuppressive agent traditionally used in inflammatory and autoimmune diseases, has also been explored as a potential treatment for alopecia areata because of its ability to suppress immune-mediated follicular damage.

This randomized controlled trial aims to compare the efficacy and safety of topical methotrexate 1% gel versus minoxidil 5% spray in patients with localized alopecia areata. Eligible participants will be randomly assigned to receive either topical methotrexate gel or minoxidil spray and will be followed for 24 weeks. Treatment response will be assessed using the Severity of Alopecia Tool (SALT) score. The findings of this study may help identify an effective therapeutic option for patients with localized alopecia areata and contribute to improving clinical management strategies for this condition.

Study Overview

• Status: Not yet recruiting
• Conditions: Alopecia Areata
• Intervention / Treatment: Drug: Methotrexate 1% Topical Gel; Drug: Minoxidil 5% Topical Spray

Detailed Description

Alopecia areata (AA) is a chronic autoimmune disorder characterized by patchy, non-scarring hair loss resulting from immune-mediated damage to hair follicles. The disease affects approximately 2% of the general population during their lifetime and can have significant psychosocial and cosmetic implications for affected individuals. Despite its relatively high prevalence, management of alopecia areata remains challenging due to variable treatment responses and the absence of a universally accepted therapeutic protocol.

Topical minoxidil is widely used in clinical practice for various types of hair loss, including alopecia areata. It promotes hair regrowth by increasing follicular blood flow, prolonging the anagen phase of the hair cycle, and stimulating hair follicle activity. Several studies have demonstrated improvement in hair density and reduction in SALT scores with the use of topical minoxidil.

Methotrexate, a folic acid antagonist with immunosuppressive and anti-inflammatory properties, has traditionally been used for the treatment of autoimmune and inflammatory conditions such as psoriasis and rheumatoid arthritis. Its immunomodulatory effects have also been explored in alopecia areata, where it may reduce the autoimmune response directed against hair follicles. Recent studies have suggested that topical methotrexate formulations may provide clinical benefit with fewer systemic adverse effects compared to oral therapy.

Given the differing mechanisms of action of these two agents-minoxidil acting primarily through follicular stimulation and methotrexate acting through immune modulation-direct comparison of their therapeutic efficacy may provide valuable insights into optimal management strategies for localized alopecia areata.

This randomized controlled trial will be conducted at the Department of Dermatology, Jinnah Postgraduate Medical Centre (JPMC), Karachi. Eligible participants aged 18-50 years with localized alopecia areata involving less than 25% of the scalp will be enrolled. Participants will be randomly assigned to receive either topical methotrexate 1% gel or minoxidil 5% spray applied twice daily for a period of 24 weeks.

The primary outcome measure will be improvement in hair regrowth assessed by change in Severity of Alopecia Tool (SALT) score from baseline to week 24. Secondary outcomes will include categorization of treatment response (no change, mild improvement, moderate improvement, significant improvement, or complete regrowth) and assessment of treatment safety through monitoring of adverse events such as local irritation, contact dermatitis, folliculitis, or systemic symptoms.

The results of this study are expected to provide evidence regarding the comparative effectiveness and safety of topical methotrexate and minoxidil in the treatment of localized alopecia areata. This may help guide clinicians in selecting appropriate therapeutic strategies and contribute to improving outcomes for patients affected by this autoimmune hair loss disorder.

• Study Type: Interventional
• Enrollment (Estimated): 268
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nimra Khan PGR, FCPS; Phone Number: +92 347 2454728; Email: drndkhan458@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients aged 18 to 50 years.

Patients of either gender.

• Patients diagnosed with localized alopecia areata, defined as one or more smooth, well-circumscribed patches of non-scarring hair loss on the scalp with less than 25% scalp involvement, assessed using the Severity of Alopecia Tool (SALT) score.
• Patients not previously treated with topical methotrexate or minoxidil for alopecia areata.
• Patients willing to provide written informed consent and comply with follow-up visits.

Exclusion Criteria:

• Patients with other types of alopecia, including androgenetic alopecia, telogen effluvium, or scarring alopecia.
• Patients with systemic diseases that may influence hair growth or treatment response, such as uncontrolled thyroid disease, uncontrolled diabetes mellitus, or autoimmune connective tissue disorders.
• Pregnant or lactating women.
• Patients who have used topical or systemic treatment for alopecia areata within the past 3 months.
• Patients with known hypersensitivity or allergy to methotrexate or minoxidil.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical Methotrexate 1% Gel; Participants in this arm will receive topical methotrexate 1% gel applied to affected scalp areas twice daily for 24 weeks. Treatment response will be assessed using the Severity of Alopecia Tool (SALT) score at baseline and during follow-up visits at weeks 4, 12, and 24.	Drug: Methotrexate 1% Topical Gel; Topical methotrexate 1% gel will be applied to the affected areas of the scalp twice daily for a duration of 24 weeks. Methotrexate acts as an immunomodulatory agent that suppresses autoimmune inflammation directed against hair follicles in alopecia areata.
Active Comparator: Topical Minoxidil 5% Spray; Participants in this arm will receive topical minoxidil 5% spray applied to affected scalp areas twice daily for 24 weeks. Treatment response will be assessed using the Severity of Alopecia Tool (SALT) score at baseline and during follow-up visits at weeks 4, 12, and 24.	Drug: Minoxidil 5% Topical Spray; Minoxidil 5% spray will be applied to the affected areas of the scalp twice daily for 24 weeks. Minoxidil promotes hair regrowth by enhancing follicular blood flow, prolonging the anagen phase of the hair cycle, and stimulating hair follicle activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Severity of Alopecia Tool (SALT) Score	The primary outcome will be the change in Severity of Alopecia Tool (SALT) score from baseline to week 24. SALT score represents the percentage of scalp hair loss. Treatment efficacy will be determined by comparing baseline SALT score with SALT score measured during follow-up. Participants achieving ≥51% reduction in SALT score at week 24 will be considered to have significant treatment response.	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Jinnah Postgraduate Medical Centre

Publications and helpful links

General Publications

• 8. Ahmed G, Khare S, Ganguly S, Chhabra N, Prabha N. Topical methotrexate 1% gel for the treatment of localized alopecia areata. Int J Dermatol. 2020;59(8):e292-e293.
• 7. Alshahrani AA, Al-Tuwaijri R, Abuoliat ZA, Alyabsi M, AlJasser MI, Alkhodair R, et al. Prevalence and clinical characteristics of alopecia areata at a tertiary care center in Saudi Arabia. Dermatol Res Pract. 2020;2020:7194270
• 6. Olayinka JT, Richmond JM. Immunopathogenesis of alopecia areata. Curr Res Immunol. 2021;2:7-11.
• 5. Davey L, Clarke V, Jenkinson E. Living with alopecia areata: an online qualitative survey study. Br J Dermatol. 2019;180(6):1377-19.
• 4. Ghassemi M, Yazdanian N, Behrangi E, Jafari M, Goodarzi A. Comparison of efficacy, safety and satisfaction of latanoprost versus minoxidil, betamethasone and in combination in patients with alopecia areata: a blinded multiple group randomized controlled trial. Dermatol Ther. 2022;35(12):e15943.
• 3. Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: a comprehensive review. Autoimmun Rev. 2015;14(2):81-89
• 2. Mao Y, Xu Z, Song J, Xie Y, Mei X, Shi W, et al. Efficacy of a mixed preparation containing piperine, capsaicin and curcumin in the treatment of alopecia areata. J Cosmet Dermatol. 2022;21(10):4510-14
• 1. Toma DM, Atallah RB, Eldahshan RM. Comparative study between topical methotrexate 1% gel and minoxidil 5% gel in the treatment of localized alopecia areata. Dermatol Ther. 2022;35(9):e15696.

Study record dates

Study Major Dates

• Study Start (Estimated): March 15, 2026
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2026

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Hair Regrowth; Autoimmune Hair Loss; Localized Alopecia Areata; Topical Methotrexate; Minoxidil 5%; SALT Score
• Additional Relevant MeSH Terms: Skin Diseases; Alopecia; Hypotrichosis; Hair Diseases; Skin and Connective Tissue Diseases; Alopecia Areata; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Dosage Forms; Piperidines; Pyrimidines; Pterins; Pteridines; Aminopterin; Complex Mixtures; Colloids; Methotrexate; Minoxidil; Gels
• Other Study ID Numbers: JPMC-DERM-AA-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data generated during this study will not be publicly shared in order to protect participant confidentiality and comply with institutional ethical guidelines. The dataset contains sensitive clinical information and the study was not originally designed with provisions for open data sharing. However, de-identified data may be made available from the corresponding author upon reasonable request, subject to approval by the institutional review board and relevant regulatory authorities.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No