Epidermal MelasmaPhase 2MET-MELNCT07779811
Topical Metformin Versus Triple Regimen for Epidermal Melasma
A Phase 2 study testing Topical 30% metformin cream and Topical Triple Regimen in people with Epidermal Melasma and Facial Hyperpigmentation, run by Combined Military Hospital, Pakistan at 1 site in Pakistan.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Epidermal Melasma, Facial Hyperpigmentation
- What is being tested?
- Topical 30% metformin cream and Topical Triple Regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 sitePakistan
- Study dates
- 15 Aug 2026to 30 Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female participants aged 18 to 50 years.
- Confirmed diagnosis of epidermal melasma according to the study's operational definition.
- Epidermal melasma confirmed by Wood's lamp examination, showing accentuated hyperpigmentation with enhanced contrast and sharp borders.
- No treatment for epidermal melasma during the previous one month.
- No dermabrasion, laser ablation, or chemical peel during the previous three months.
- Willing to provide written informed consent.
Who cannot join
- Acne vulgaris.
- Rosacea.
- Pregnancy.
- Presence of comorbid conditions.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Comparison of Efficacy of Topical Triple Regimen Versus 30% Metformin in the Treatment of Epidermal Melasma
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
Read the detailed description
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.
- Conditions
- Epidermal Melasma, Facial Hyperpigmentation
- Being tested
- Topical 30% metformin cream, Topical Triple Regimen
- Keywords
- Melasma, Epidermal Melasma, Facial Hyperpigmentation, Topical Metformin, Triple Combination Therapy, Modified MASI, Randomized Clinical Trial, Topical Treatment
- Medical subject headings
- Melanosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical 30% metformin creamDrug
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.
Topical Triple RegimenDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Topical 30% Metformin | Experimental | 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. Receives: Drug: Topical 30% metformin cream |
| Topical Triple Regimen | Active comparator | 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. Receives: Drug: Topical Triple Regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2026
- Study start15 Aug 2026 (estimated)
- Primary completion15 Jan 2027 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epidermal MelasmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be assigned to one of two parallel treatment groups. Group A will receive topical 30% metformin cream, while Group B will receive a topical triple regimen containing 2% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide. Both groups will receive treatment once daily at night for eight weeks, together with morning use of SPF 50 or higher sunscreen.
- Masking
- None (open label)
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Combined Military Hospital, Pakistan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Rabia Hamid, Combined Military Hospital, Pakistan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07779811
- Sponsor's protocol ID
- CMH-MEL-MET-TCR-001
- Acronym
- MET-MEL
- Status last verified
- Aug 2026
- First submitted
- 6 Aug 2026
- Last updated
- 21 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Efficacy of Topical Triple Regimen Versus 30% Metformin in the Treatment of Epidermal Melasma
- ClinicalTrials.gov ID
- NCT07779811
- Acronym / sponsor ID
- MET-MEL / CMH-MEL-MET-TCR-001
- Conditions
- Epidermal Melasma, Facial Hyperpigmentation
- Keywords
- Melasma, Epidermal Melasma, Facial Hyperpigmentation, Topical Metformin, Triple Combination Therapy, Modified MASI, Randomized Clinical Trial, Topical Treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Combined Military Hospital, PakistanUniversity, hospital or other
- Study start
- 15 Aug 2026 (estimated)
- Primary completion
- 15 Jan 2027 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 21 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be assigned to one of two parallel treatment groups. Group A will receive topical 30% metformin cream, while Group B will receive a topical triple regimen containing 2% hydroquinone, 0.05% tretinoin, and 0.01% fluocinolone acetonide. Both groups will receive treatment once daily at night for eight weeks, together with morning use of SPF 50 or higher sunscreen.
| Arm | Type | Receives |
|---|---|---|
| Topical 30% Metformin | Experimental | Drug: Topical 30% metformin creamParticipants 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. |
| Topical Triple Regimen | Active comparator | Drug: Topical Triple RegimenParticipants 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male or female participants aged 18 to 50 years.
- Confirmed diagnosis of epidermal melasma according to the study's operational definition.
- Epidermal melasma confirmed by Wood's lamp examination, showing accentuated hyperpigmentation with enhanced contrast and sharp borders.
- No treatment for epidermal melasma during the previous one month.
- No dermabrasion, laser ablation, or chemical peel during the previous three months.
Key exclusion criteria (4 listed)
- Acne vulgaris.
- Rosacea.
- Pregnancy.
- Presence of comorbid conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topical 30% metformin creamTopical 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. | Drug | Topical 30% Metformin |
| Topical Triple RegimenA 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. | Drug | Topical Triple Regimen |
Primary outcome
Proportion of Participants Achieving at Least 25% Reduction in Modified Melasma Area and Severity Index (mMASI) Score
Time frame: Baseline to 8 weeks
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2026.
- Background study comparing topical 30% metformin cream with triple-combination cream for melasma.Link provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Epidermal Melasma
Recruiting
COMPARISON OF A COSMETIC SERUM AND 4% HYDROQUINONE FOR TREATING MELASMA OVER 84 DAYS
Healthy, Melasma (Facial Melasma)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Topical 30% metformin cream and Topical Triple Regimen in people with Epidermal Melasma and Facial Hyperpigmentation, run by Combined Military Hospital, Pakistan at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Achieving at Least 25% Reduction in Modified Melasma Area and Severity Index (mMASI) Score (time frame: Baseline to 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.