Clinical Trial of Hydroquinone Versus Miconazol in Melasma

Study Overview
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Brief Summary
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Melasma is an acquired discoloration of the skin characterized by brown colour changes commonly on the face.The duration of this double-blind clinical trial will be 12 weeks. The control group will receive treatment with topical Hydroquinone (4%), and the other group topical miconazole. Miconazol has antimelanotic properties and can be used as treatment for melasma patients. The estimated number of subjects to be recruited and randomized for the study is at least 30. The purpose of this study is determine if there is a difference in the effectiveness of these two agents. Melasma Area and Severity Index (MASI) score will be assessed at the beginning of the study and at weeks 4, 8, and 12. Photographs, colorimetry and histological assessment will be also evaluated. Occurrence of adverse effects will also be recorded.

Detailed Description
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Melasma is a common acquired hypermelanosis in dark skin populations, usually characterized by symmetrical, irregular macules occurring in photo-exposed areas such as face. Treatment with depigmenting compounds such as hydroquinone, are still the gold standard in this condition. Miconazol has depigmented properties that could be used as part of the treatment in melasma patients. This effect is exerted by inhibiting the tyrosinase enzyme. So, the primary objective of this study is to compare the depigmenting activity of miconazole against hydroquinone. Patients who are included in the study will be randomly assigned to receive one of the treatments, which should use for 12 weeks. The medications should be applied in the affected regions twice a day. The evaluation of clinical improvement will be done in a blinded modality by means of the MASI score, the Global Physician Assessment, as well as colorimetry and histological melanin content. Evaluations will be held on visits at 4, 8 and 12 weeks. Skin biopsy will be taken at onset and at 12 weeks. At the end of the study, data will be compared concerning the former parameters. All side effects will be recorded and analysed.

Official Title
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Double Blind Randomized Study of 2% Miconazol Versus 4% Hydroquinone in the Treatment for Melasma.

Conditions
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Melasma

Intervention / Treatment
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* Drug: Miconazole
* Drug: Hydroquinone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Mexican women over 18 years of age Dermatologic diagnostic of melasma Phototype III or more Exclusion Criteria: Pregnant or breastfeeding Postbirth, abortion in the past 6 months Having an endocrine or autoimmune disease Under hormonal therapy of any kind including contraceptives or it´s use in the past 6 months Currently under treatment for melasma including sunblock Currently under radiation therapy, chemotherapy, immunosuppressants of any kind or phototherapy or it´s use in the past 6 months Having used or are consuming photosensitizing substances, oral or topical

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Miconazole<br>OTC topical prescription used for fungal treatment that can be useful to the treatment of melasma due to its depigmenting properties. | Drug: Miconazole<br>* Miconazole 2% cream will be applied twice a day for 9 weeks. The affected surface will be washed and dried before application with a thin layer of the emulsion as indicated on the affected areas of the face.<br>* Other names: Micatin;|
| Active Comparator: Hydroquinone<br>Hydroquinone 4% cream (Topical use) a depigmenting agent used as reference will be used as control. It will be applied twice a day for 9 weeks. | Drug: Hydroquinone<br>* Hydroquinone 4% cream (Topical use), will be applied twice a day for 9 weeks. The affected surface will be washed and dried before application with a thin layer of the emulsion on affected areas of the face.<br>* Other names: Melanex;|
| Placebo Comparator: Placebo<br>Moisturizer cream without pharmacological effects will be used as a control. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depigmentation of melasma lesions by Colorimetry | Quantification of the colour change in the melasma lesions by means of the L axis of the CIE system. 0 is pure white, 100 y total dark. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Physician Assessment | Clinical improvement is assessed by means of digital photographic registration (frontal, right, and left views). An independent observer clinically graded the global improvement as poor (0-25%), mild (26-50%), good (51-75%), and excellent (>75%). | 12 weeks | 
| MASI (Melasma Area Severity Index) | The total score would range from 0-24, involving the forehead (30%), right malar (30%), left malar (30%) and chin (10%), and using area of involvement (0=absent, 1=<10%, 2=10%-29%, 3=30%-49%, 4=50%-69%, 5=70%-89% and 6=90%-100%) and darkness (0=absent, 1=slight, 2=mild, 3=marked and 4=severe). Computation would be as follows: 0.3 A(f) D(f) + 0.3 A(lm) D(lm) + 0.3 A(rm) D(rm) + 0.1 A(c) D(c). | 12 weeks | 
| Melanin content by Fontana Masson stain | The Fontana-Masson Stain is specific for melanin, this histochemical reaction reveals accumulations of black material wherever melanin is located. A skin biopsy of lesions will be taken initially and at the end of study. The melanin content will be quantified by a software image analysis of the slides. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melasma, miconazole, hydroquinone