Microneedling-Assisted Metformin, Tranexamic Acid, and Modified Kligman's Formula for Melasma

Official title

Microneedling-Assisted Delivery of Metformin, Tranexamic Acid, and Modified Kligman's Formula for Melasma Treatment: A Clinical and Microscopic Evaluation

Overview

Melasma is a common skin condition characterized by brown or gray patches on sun-exposed areas of the face. Although several topical treatments are available, treatment outcomes are often unsatisfactory, and recurrence is common. This randomized, parallel-group clinical trial aims to compare the efficacy and safety of microneedling-assisted topical metformin, topical tranexamic acid, and modified Kligman's formula with microneedling-assisted saline in adult women with melasma. Eighty participants will be randomly assigned to one of four treatment groups. The primary outcome is the change in Melasma Area and Severity Index (MASI) score from baseline to the end of follow-up. Secondary outcomes include clinical improvement, dermoscopic changes in pigmentation and vascular features, patient satisfaction, and treatment-related adverse events.

Detailed description

Melasma is a chronic acquired hyperpigmentation disorder characterized by symmetric brown to gray-brown macules and patches affecting sun-exposed areas of the skin, particularly the face. It predominantly affects women of reproductive age and has a considerable negative impact on quality of life. The pathogenesis of melasma is multifactorial, involving genetic predisposition, ultraviolet radiation, hormonal influences, increased melanogenesis, vascular alterations, and inflammatory pathways. Despite the availability of multiple treatment options, recurrence is common and no universally effective therapy has been established.

Microneedling is a minimally invasive procedure that enhances transdermal drug delivery by creating controlled microchannels within the skin, thereby improving the penetration and bioavailability of topical agents. Topical metformin has recently emerged as a potential depigmenting agent through inhibition of melanogenesis and reduction of tyrosinase activity. Tranexamic acid inhibits ultraviolet-induced melanogenesis by suppressing the plasminogen-plasmin pathway and reducing melanocyte activation. Modified Kligman's formula, consisting of hydroquinone, tretinoin, and a topical corticosteroid, remains the standard topical treatment for melasma but is frequently associated with local adverse effects.

This prospective, randomized, parallel-group clinical trial was designed to compare the efficacy and safety of microneedling-assisted topical metformin, topical tranexamic acid, modified Kligman's formula, and saline as a control in women with melasma. Eighty eligible participants were randomly allocated in a 1:1:1:1 ratio to one of four treatment groups. All participants underwent standardized microneedling using a dermapen before application of the assigned topical treatment. Treatment sessions were performed every two weeks for a maximum of five sessions, followed by a three-month follow-up period.

The primary objective was to evaluate changes in the Melasma Area and Severity Index (MASI). Secondary objectives included assessment of clinical improvement, dermoscopic changes in pigmentation and vascular features, patient satisfaction, and treatment-related adverse events. The findings of this study are expected to provide comparative evidence regarding the effectiveness and safety of these microneedling-assisted topical therapies and help optimize treatment strategies for patients with melasma.

Interventions

• Drug Metformin 30% Topical Lotion
  Participants received topical metformin 30% lotion immediately after standardized microneedling with a dermapen. Approximately 3 mL of the lotion was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the medication on the skin for 4 hours before washing.
• Drug Tranexamic Acid 0.5% Topical Solution
  Participants received topical tranexamic acid 0.5% solution immediately after standardized microneedling with a dermapen. Approximately 3 mL of the solution was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the medication on the skin for 4 hours before washing.
• Drug Modified Kligman's Formula
  Participants received modified Kligman's formula consisting of hydroquinone 4%, tretinoin 0.05%, and mometasone furoate 0.1% immediately after standardized microneedling with a dermapen. Approximately 3 mL was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the medication on the skin for 4 hours before washing.
• Drug Normal Saline
  Participants received topical normal saline immediately after standardized microneedling with a dermapen. Approximately 3 mL of saline was applied during each treatment session. Five treatment sessions were performed at 2-week intervals. Participants were instructed to leave the saline on the skin for 4 hours before washing.

Primary outcome measures

• Change in Melasma Area and Severity Index (MASI) Score [Time frame: Baseline to 3 months after the final treatment session (approximately 5 months after randomization)]
• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: Baseline to 3 months after the final treatment session (approximately 5 months after randomization)]

Eligibility criteria

Inclusion criteria

• Female participants aged 18 years or older.
• Clinical diagnosis of melasma.
• No medical treatment for melasma during the previous 6 months.
• Willing and able to comply with all study procedures and follow-up visits.
• Provided written informed consent before study participation.

Exclusion criteria

• Pregnant or breastfeeding women.
• Use of hormonal contraceptives.
• Use of medications known to affect skin pigmentation (e.g., phenytoin, amiodarone, antipsychotics, cytotoxic agents, tetracyclines, or heavy metals).
• History of keloid formation or foreign body reaction.
• Known allergy or hypersensitivity to any study medication.
• Presence of systemic diseases affecting pigmentation, including hepatic, renal, thyroid, or other endocrine disorders.
• Fitzpatrick skin types V or VI.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Faculty of Medicine — Tanta

Identifiers

NCT: NCT07696806 · TU-DERM-MEL-2020-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗