DNA Methylation in Malar Melasma and Its Change by Sunscreen, Retinoic Acid and Niacinamide.

Study Overview
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Brief Summary
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BACKGROUND: Malar melasma has a chronic and recurrent character that may be related with epigenetic changes.

Detailed Description
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OBJECTIVE: Recognize the DNA methylation status of the malar melasma and perilesional skin, and its change after treatment with 50 SPF sunscreen (S), 4% niacinamide (N), or 0.025% retinoic acid (RA). METHODS: Fifty-six lesion of 28 female patients without treatment were clinically evaluated, as also the expression of DNA methyl transferases 1 and 3 by real time-PCR (polymerase chain reaction amplification), immunohistochemistry and immunofluorescence. It was initially quantified and after 8 weeks of treatment with S, RA and N. RESULTS: Relative expression of DNA methyl transferases were significantly elevated compared with unaffected skin in all subjects indicating hypermethylation of DNA. Hypermethylation decreased by S (7 vs 3 times relative expression, p<0.05), RA (7 vs 2 times relative expression p<0.05), and N (7 vs 1 relative expression p<0.01) correlated with clinical improvement, this was also supported by immunohistochemistry and immunofluorescence. CONCLUSIONS: The investigators found hypermethylation of DNA in melasma lesions. Environmental factors such as sun radiation may induce DNA hypermethylation triggering hyperpigmentation trough the activation of pathways regulated by epigenetic modifications. Thus, decreasing methylation by sunscreen protection and the genetic transcription modification through N and RA, may allow their clinical improvement regardless its depigmenting effect.

Official Title
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DNA Methylation in Malar Melasma and Its Change by Sunscreen, Retinoic Acid and Niacinamide.

Conditions
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Melasma

Intervention / Treatment
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* Drug: Retinoic acid
* Device: colorimetry measurement
* Drug: sunscreen
* Drug: Niacinamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of malar melasma by a specialist. No previous treatment at the beginning of the study. Exclusion Criteria: Use of medications associated with the development of melasma. Pregnant or lactating patients. Presence of concomitant diseases associated with the development of melasma. or other facial hyperpigmentations (thyroid, liver). Have received treatment in the last 2 months. Regular use of sunscreen.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control group<br>Macules of melasma without any treatment | Device: colorimetry measurement<br>* Measurement of erythema and luminosity through a colorimeter<br>|
| Experimental: Niacinamide group<br>Macules of melasma treated with topical Niacinamide cream 4% for 8 weeks | Device: colorimetry measurement<br>* Measurement of erythema and luminosity through a colorimeter<br>Drug: Niacinamide<br>* topical administration in melasma lesions<br>|
| Experimental: Retinoic acid group<br>Macules of melasma treated with topical retinoic acid 0.05% for 8 weeks | Drug: Retinoic acid<br>* topical administration in melasma lesions<br>* Other names: Sunscreen;Device: colorimetry measurement<br>* Measurement of erythema and luminosity through a colorimeter<br>|
| Placebo Comparator: Sunscreen group<br>Macules of melasma treated with sunscreen cream with a 50 sun protection factor for 8 weeks | Device: colorimetry measurement<br>* Measurement of erythema and luminosity through a colorimeter<br>Drug: sunscreen<br>* topical administration in melasma lesions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improve in the level of DNA methylated | Decrease in levels of expression of DNA methyl transferases | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| improve in the clinical severity of melasma | decrease in the MASI score | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epigenetics, Malar melasma,