A Phase 2 interventional study of Topical 30% metformin cream and Topical Triple Regimen in Epidermal Melasma and Facial Hyperpigmentation, sponsored by Combined Military Hospital, Pakistan. Not yet recruiting at 1 site in Pakistan. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2026-08-21.
Sponsored by Combined Military Hospital, Pakistan · Phase 2, Interventional, and Treatment
Melasma is a common skin condition that causes dark brown patches, mainly on sun-exposed areas of the face. It is often persistent, may recur after treatment, and can affect a person's quality of life. The standard topical triple regimen used for melasma contains hydroquinone, tretinoin, and fluocinolone acetonide. Although effective, prolonged use may cause adverse effects such as redness, burning, peeling, telangiectasia, and steroid-related skin changes. Topical metformin has recently been investigated as a possible alternative treatment because it may reduce skin pigmentation with relatively few side effects.
This randomized clinical trial will compare the efficacy of topical 30% metformin cream with a topical triple regimen in adults with epidermal melasma. A total of 104 participants aged 18-50 years will be enrolled, with 52 participants assigned to each treatment group. Group A will receive topical 30% metformin, while Group B will receive a triple regimen containing 2% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide. Participants will apply the assigned treatment once daily at night for eight consecutive weeks. All participants will also be advised to use SPF 50 or higher sunscreen in the morning.
Treatment efficacy will be assessed by comparing the modified Melasma Area and Severity Index score at baseline and after eight weeks. Treatment will be considered effective when the participant achieves at least a 25% reduction in the modified MASI score from baseline. The findings may help identify a more effective and acceptable topical treatment option for patients with epidermal melasma
Melasma is an acquired hyperpigmentation disorder characterized by symmetrical brown or dark-brown patches, most commonly affecting the centrofacial, malar, or mandibular regions of the face. Epidermal melasma is identified by enhanced contrast and sharply defined pigmentation under Wood's lamp examination, indicating superficial epidermal melanin deposition. The condition is particularly common among women of reproductive age and is associated with ultraviolet exposure, heat exposure, pregnancy, hormonal factors, oral contraceptive use, and genetic susceptibility.
Topical triple-combination therapy has been widely used as a standard treatment for melasma. However, prolonged treatment may be limited by adverse effects, including erythema, desquamation, burning, telangiectasia, and steroid-related complications. Topical metformin has emerged as a possible alternative because experimental studies suggest that it may reduce melanogenesis by downregulating melanogenic proteins and decreasing expression of microphthalmia-associated transcription factor. Previous clinical studies have reported improvement in melasma severity with topical metformin, but comparative evidence remains limited.
This study is a randomized clinical trial that will be conducted in the Dermatology Department of Combined Military Hospital Malir Cantt, Karachi. The study aims to compare the efficacy of topical 30% metformin with a topical triple regimen in patients with epidermal melasma. The planned sample consists of 104 participants, with 52 participants in each treatment group. Participants will be recruited through non-probability consecutive sampling and then randomly allocated to either group using the lottery method.
Eligible participants will include men and women aged 18-50 years with epidermal melasma confirmed according to the study's operational definition. Participants must not have used treatment for epidermal melasma during the previous month and must not have undergone dermabrasion, laser ablation, or chemical peeling during the previous three months. Patients with acne vulgaris, rosacea, pregnancy, or comorbid conditions will be excluded.
After written informed consent, demographic and clinical information will be recorded, including age, sex, marital status, education, residence, employment status, duration of melasma, estimated daily sun exposure, treatment history, and site of facial involvement. Each participant will undergo clinical examination using a Wood's lamp, and a baseline modified Melasma Area and Severity Index score will be calculated.
Participants assigned to Group A will receive topical 30% metformin cream. Participants assigned to Group B will receive a topical triple regimen containing 2% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide. Both treatments will be applied once daily at night for eight consecutive weeks. All participants will be advised to apply SPF 50 or higher sunscreen in the morning. Digital photographs will be taken before treatment and after completion of therapy.
The primary outcome is treatment efficacy at eight weeks. Efficacy will be measured using the percentage reduction in modified MASI score from baseline:
Percentage reduction = [(baseline score - post-treatment score) ÷ baseline score] × 100
Treatment will be classified as effective when the participant achieves a reduction of at least 25% from the baseline modified MASI score. The modified MASI score will be recorded at the first visit and at the final assessment after eight weeks.
Quantitative variables, including age, disease duration, and modified MASI scores, will be summarized using mean and standard deviation. Qualitative variables, including sex, marital status, education, residence, sun exposure, melasma site, and efficacy, will be summarized using frequencies and percentages. The efficacy proportions of the two groups will be compared using the chi-square test, with a p-value of 0.05 or less considered statistically significant. Stratification will be used to control for potential confounders such as age, sex, disease duration, marital status, education, residence, sun exposure, and site of melasma.
170 studies on the registry are indexed under Melanosis; 46 are open to participants now.
This study's planned enrollment of 104 is above the median of 40 across 157 interventional studies indexed under Melanosis.
Browse Melanosis studies →Combined Military Hospital, Pakistan is the lead sponsor of 15 studies on the registry; 4 are open to participants now.
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Exclusion Criteria:
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Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants assigned to this arm will apply topical 30% metformin cream once daily at night for eight consecutive weeks. Participants will also be advised to use SPF 50 or higher sunscreen in the morning.
Drug: Topical 30% metformin cream
Participants assigned to this arm will apply a topical triple regimen containing 2% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide once daily at night for eight consecutive weeks. Participants will also be advised to use SPF 50 or higher sunscreen in the morning.
Drug: Topical Triple Regimen
Topical metformin cream at a concentration of 30% will be applied once daily at night to affected facial areas for eight consecutive weeks. Participants will use SPF 50 or higher sunscreen in the morning.
A topical triple-combination regimen containing 2% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide will be applied once daily at night to affected facial areas for eight consecutive weeks. Participants will use SPF 50 or higher sunscreen in the morning.
Proportion of Participants Achieving at Least 25% Reduction in Modified Melasma Area and Severity Index (mMASI) Score
The modified Melasma Area and Severity Index (mMASI) score will be assessed at baseline and Week 8. Percentage reduction in mMASI score will be calculated as: \[(baseline mMASI score - Week 8 mMASI score) / baseline mMASI score\] × 100. A participant will be classified as a responder if the mMASI score decreases by at least 25% from baseline to Week 8. The outcome will be reported as the proportion of participants meeting this response criterion in each treatment group.
Time frame: Baseline to 8 weeks
Plan to share: No
Start is estimated for Aug 2026; primary completion for Jan 2027, 5 months later.
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Combined Military Hospital, Pakistan