Effectiveness of Oral Melatonin vs Oral Tranexamic Acid in the Treatment and Recurrence of Melasma

Phase 4

Active, not recruiting

• Conditions: Melasma; Treatment Outcome; Recurrence
• Interventions: Drug: Tranexamic Acid (TXA); Drug: melatonin (Circadin); Drug: Placebo

• Registration Number: NCT07034560
• Lead Sponsor: Thammasat University

Brief Summary

This study compares the effectiveness of two oral medications-melatonin and tranexamic acid -in treating melasma, a common skin condition that causes dark facial patches.

Participants will be randomly assigned to receive either melatonin, tranexamic acid, or a placebo once daily at bedtime for 12 weeks. During this treatment phase, all participants will also apply a broad-spectrum sunscreen and a base cream.

After 12 weeks, participants will stop the oral medication but continue using the sunscreen and base cream for an additional 12 weeks to assess recurrence of melasma.

The study evaluates improvement in skin pigmentation, recurrence after treatment cessation, quality of life, and patient satisfaction.

This clinical trial will be conducted at Benchakitti Park Hospital, Bangkok, Thailand, and will enroll 75 adult participants.

Detailed Description

Melasma is a chronic skin disorder characterized by symmetrical, hyperpigmented patches on sun-exposed areas, especially the face. Although its exact cause is not fully understood, hormonal influences, ultraviolet (UV) exposure, and genetic predisposition are contributing factors.

Tranexamic acid (TXA), an antifibrinolytic agent, has shown promising results in treating melasma by inhibiting melanogenesis through the plasminogen-plasmin pathway. Melatonin (MLT), a hormone with antioxidant and anti-inflammatory properties, has also demonstrated potential benefits in melasma management by reducing oxidative stress and interfering with the melanin synthesis pathway.

This prospective, randomized, controlled, evaluator-blinded clinical trial aims to compare the efficacy and recurrence outcomes of oral TXA (500 mg), oral MLT (2 mg), and placebo, each administered once daily for 12 weeks. After discontinuing the oral treatment, all participants will continue using sunscreen and base cream for an additional 12 weeks to evaluate recurrence.

Outcome measures include modified Melasma Area and Severity Index (mMASI), Mexameter-based pigmentation indices, quality of life scores (DLQI), and patient satisfaction (VAS). The study is conducted at Benchakitti Park Hospital and includes 75 adult participants with epidermal or mixed-type melasma.

Study Timeline

• Study Start: 2024-11-12
• Status Verified: 2025-06
• Study First Submitted: 2025-06-10
• Study First Submitted QC: 2025-06-19
• Last Update Submitted: 2025-06-19
• Study First Posted: 2025-06-24
• Last Update Posted: 2025-06-24
• Primary Completion: 2025-11-06
• Study Completion: 2025-11-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

1. Patients with the age above 18 years and above
2. Patients diagnosed with epidermal or mixed-type melasma

Exclusion Criteria

1. Use of topical medications such as hydroquinone, whitening agents (e.g., arbutin, kojic acid, vitamin C, retinoids, and steroids) on melasma areas within 4 weeks prior to joining the study
2. Chemical peeling within 4 weeks prior to joining the study
3. Use of oral tranexamic acid or any supplements within 3 months prior to joining the study
4. History of laser treatment, dermabrasion, or skin-tightening devices within 6 months prior to joining the study
5. History of botulinum toxin injections, fillers, collagen stimulators, or thread lifts within 12 months prior to joining the study
6. Pregnancy or breastfeeding
7. Use of hormonal contraceptives within 1 year prior to joining the study
8. Personal or family history of thrombotic disorders, such as deep vein thrombosis, pulmonary embolism, stroke, protein C or S deficiency, or antithrombin III deficiency
9. History of more than 2 spontaneous abortion
10. History of impaired kidney function
11. History of cancer
12. Smoking
13. Heart disease (e.g., end-stage heart failure, chronic obstructive pulmonary disease, or use of prosthetic heart valves)
14. History of allergy to oral tranexamic acid or melatonin
15. Patients who are unable to follow up as per the study protocol
16. Patients with Hori's nevus

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tranexamic Acid (TXA)	Tranexamic Acid (TXA)	Participants will receive 500 mg of oral tranexamic acid (Transamin®) once daily at bedtime for 12 weeks, along with a broad-spectrum sunscreen and a base cream.
melatonin (Circadin)	melatonin (Circadin)	Participants will receive 2 mg of oral melatonin (Circadin®) once daily at bedtime for 12 weeks, along with a broad-spectrum sunscreen and a base cream.
Placebo	Placebo	Participants will receive a placebo capsule once daily at bedtime for 12 weeks, along with a broad-spectrum sunscreen and a base cream.

Primary Outcome Measures

Name	Time	Method
Change in modified Melasma Area and Severity Index (mMASI)	Baseline, Week 4, Week 8, Week 12	Change in modified Melasma Area and Severity Index (mMASI) score from baseline to Week 12.; The mMASI ranges from 0 to 14.4, with higher scores indicating more severe melasma.
Change in modified Melasma Area and Severity Index (mMASI) (Recurrence)	Week 12, Week 16, Week 20, Week 24	Recurrence is defined as an increase in mMASI score ≥50% from Week 12 to Week 24.; The mMASI ranges from 0 to 14.4; higher scores indicate worse melasma.

Secondary Outcome Measures

Name	Time	Method
Melanin and Erythema Index	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	Change in Melanin Index and Erythema Index at baseline to 24 weeks, measured by Mexameter.; Higher values indicate increased pigmentation and erythema, respectively
Change in skin texture, pore size, fine line (Antera 3D imaging)	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	Quantitative skin analysis using Antera 3D® imaging at baseline to 24 weeks. Lower scores indicate smoother texture, smaller pores, and fewer fine lines.
Dermatology Life Quality Index (DLQI) score	Baseline, Week 12, Week 24	Change in Dermatology Life Quality Index (DLQI) from baseline to 24 weeks. DLQI ranges from 0 to 30. Higher scores indicate greater impairment in quality of life.
Patient satisfaction (Visual Analog Scale)	Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24	Patient satisfaction score at every 4 weeks using Visual Analog Scale (VAS) from 0 to 10.; Higher scores indicate greater satisfaction.
Adverse events (AEs)	Week 4, Week 8, Week 12	Number and severity of treatment-emergent adverse events during the 12-week intervention

Trial Locations

Locations (1)

Benchakitti Park Hospital; 🇹🇭 Bangkok, Thailand