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

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

Study Overview

• Status: Completed
• Conditions: Melasma
• Intervention / Treatment: Device: colorimetry measurement; Drug: Niacinamide; Drug: Retinoic acid; Drug: sunscreen

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Early Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universidad Autonoma de San Luis Potosí

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 2, 2018
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 8, 2018

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: January 6, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Epigenetics, Malar melasma,
• Additional Relevant MeSH Terms: Skin Diseases; Hyperpigmentation; Pigmentation Disorders; Melanosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Antineoplastic Agents; Protective Agents; Dermatologic Agents; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Keratolytic Agents; Vitamin B Complex; Radiation-Protective Agents; Nicotinic Acids; Tretinoin; Niacinamide; Niacin; Sunscreening Agents
• Other Study ID Numbers: 71-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes