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

Early Phase 1

Completed

• Conditions: Melasma
• Interventions: Device: colorimetry measurement; Drug: Retinoic acid; Drug: sunscreen; Drug: Niacinamide

• Registration Number: NCT03392623
• Lead Sponsor: Universidad Autonoma de San Luis Potosí

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study Start: 2015-01-01
• Primary Completion: 2016-01-01
• Study Completion: 2016-12-01
• Status Verified: 2018-01
• Study First Submitted: 2018-01-02
• Study First Submitted QC: 2018-01-02
• Last Update Submitted: 2018-01-06
• Study First Posted: 2018-01-08
• Last Update Posted: 2018-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 28

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sunscreen group	colorimetry measurement	Macules of melasma treated with sunscreen cream with a 50 sun protection factor for 8 weeks
Retinoic acid group	colorimetry measurement	Macules of melasma treated with topical retinoic acid 0.05% for 8 weeks
Niacinamide group	colorimetry measurement	Macules of melasma treated with topical Niacinamide cream 4% for 8 weeks
Control group	colorimetry measurement	Macules of melasma without any treatment
Sunscreen group	sunscreen	Macules of melasma treated with sunscreen cream with a 50 sun protection factor for 8 weeks
Niacinamide group	Niacinamide	Macules of melasma treated with topical Niacinamide cream 4% for 8 weeks
Retinoic acid group	Retinoic acid	Macules of melasma treated with topical retinoic acid 0.05% for 8 weeks

Primary Outcome Measures

Name	Time	Method
improve in the level of DNA methylated	8 weeks	Decrease in levels of expression of DNA methyl transferases

Secondary Outcome Measures

Name	Time	Method
improve in the clinical severity of melasma	8 weeks	decrease in the MASI score