Comparison of Topical Silymarin With Hydroquinone in the Treatment of Melasma

A randomized clinical trial will be done on 92 patients , randomly divided into two groups by lottery method to compare the efficacy and safety of topical silymarin cream 0.7% with topical 4% hydroquinone cream. Patients will be treated for 3 months and for the next 3 months will be followed up for relapse of melasma.

Study Overview

• Status: Completed
• Conditions: Melasma
• Intervention / Treatment: Drug: Hydroquinone 4% Cream; Drug: silymarin 0.7% cream

Detailed Description

A comparative study done by Nofal A et al, comparing the effectiveness and safety of topical silymarin versus hydroquinone, concluded that silymarin cream can be used as more potent and safer treatment option for the treatment of melasma.8 Two different concentrations of silymarin cream (0.7% and 1.4%) were used in this study and the results showed that both the groups have no statistically significant difference in terms of therapeutic response (mean of percentage reduction in MASI was 39.21 for 0.7% silymarin cream group and 33.84 for 1.4% silymarin cream group). Additionally relapse cases were identified in 7.14% of patients in both the groups. This shows that silymarin used at low concentration can prove to be more potent than at high concentration when it comes to effectiveness, cost and adverse effects. Therefore, I will compare 0.7% silymarin cream with 4% hydroquinone cream in my clinical trial for the treatment of melasma.

Rationale of this study is to observe the effects of this alternative treatment option and compare it with the first line drug so that it can be recommended in the guidelines as an alternative treatment option for melasma. The study by Nofal at al. was done in Egypt where most if the people have type 4 skin and environmental conditions are also similar to Pakistan. However a very small population group was included in the study. I want to do the same interventional trial on a larger population size to validate silymarin as an effective and safer treatment option.

Patients attending ANTH dermatology out patient, fulfilling the inclusion criteria will be inducted. Informed written consent will be taken from the enrolled patients and confidentiality will be maintained throughout the study. A detailed history will be taken focusing on duration and onset, family history, any relation to pregnancy, effect of exposure to sun, systemic inquiry and prior treatment sought. Fitzpatrick skin type and melisma pattern will be assessed. Melasma type will be assessed with the help of Wood's light examination. The severity of melasma will be assessed using MASI score. Random distribution of patients will be done through lottery method. Group A will be treated with topical hydroquinone 4% cream applied once daily at night and group B with silymarin 0.7% cream applied twice daily. All the patients will be advised to have proper sun protection measures, use physical protection like umbrella or a P cap and a wear sunscreen having a sun protective factor of at least 60. Patients will be advised not to use topical retinoids or any other product containing peroxide in it and not to apply the cream near eyes, mouth or nose. Patients will be asked to do a patch test on volar aspect of arms for 3 days before starting the treatment on face and immediately stop the treatment and report if she develops erythema and/or burning sensation with either drug. Digital photography will be taken at baseline and after every month during the treatment course till three months.

Patients will be booked for follow up at 1 month interval for 6 months. Treatment will be given for 3 months and will be followed up for the next 3 months (during which patients will be using only sun protection measures) to observe relapse of melasma. On follow up visits during treatment period, history will be taken regarding compliance to treatment and drug tolerance. The MASI score will be calculated at baseline and each follow up visit. Clinical efficacy will be assessed in terms of percent reduction in MASI score from baseline. Any adverse effect of treatment and patient's satisfaction using the short assessment of patient<s satisfaction will be measured at each visit. Information will be recorded on specially designed performas.

The data will be analyzed with the help of Statistical Package for Social Sciences (SPSS) version 25. Data will be presented as mean ± SD for quantitative variables (age, percent reduction of MASI, Short Assessment of Patient Satisfaction) and frequency with percentages for categorical variables (sun exposure, family history, previous therapy, melasma type, melasma pattern, melasma severity, burning and erythema). Independent sample t-test will be used to compare percent reduction in MASI score between both treatment groups at each follow up. Paired sample t-test will be used to compare the MASI score with baseline at each follow up visit within both groups. Chi-square test will be applied to compare the clinical efficacy, and safety in terms of any side effect between both groups throughout the study period. P-value of <0.05 will be considered significant.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• Pakistan
  • Federal
    • Islamabad, Federal, Pakistan, 44000
      • Islamabad Medical and Dental College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female sex.
• Age 18 or older.
• Melasma of different severities, types and patterns

Exclusion Criteria:

• Pregnant or lactating females (Hydroquinone has pregnancy category C and it is not known if it is distributed in breast milk or not).
• Ongoing use of hormonal birth control pills or any hormonal therapy (as they cause hyperpigmentation).

• Use of topical anti melasma therapy within 3 months (efficacy of current therapy cannot be concluded).

  • Use of topical steroids within 3 months (as topical steroids will decrease hyperpigmentation).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hydroquinone group; Hydroquinone 4% cream Cream applied once daily at night on affected areas for 3 months.	Drug: Hydroquinone 4% Cream; Hydroquinone is tyrosinase inhibitor and thus inhibits melanogenesis.
Experimental: Silymarin group; Silymarin 0.7% cream Cream applied twice daily on affecectec areas for 3 months.	Drug: silymarin 0.7% cream; Silymarin is a plant derived flavonoid, extracted from fruits and seeds of milk thistle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic response will be assessed in terms of percent reduction in MASI score from baseline to 1,2 and 3 month of treatment course and for next 3 months of follow up.	>75% improvement as excellent; 50-75% improvement as good; 25-50% improvement as medium; < 25% improvement as poor	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
b) Measurement of patient's satisfaction monthly for 6 months by the Short Assessment of Patient Satisfaction (SAPS).	0 - 10 very unsatisfied.; 11 - 18 unsatisfied.; 19 - 26 satisfied.; 27 - 28 very satisfied.	6 months

Collaborators and Investigators

• Sponsor: Islamabad Medical and Dental College
• Investigators: Principal Investigator: Sumaira Abdullah, MBBS, MCPS, MD, Senior Registrar in Dermatology

Publications and helpful links

General Publications

• Nofal A, Ibrahim AM, Nofal E, Gamal N, Osman S. Topical silymarin versus hydroquinone in the treatment of melasma: A comparative study. J Cosmet Dermatol. 2019 Feb;18(1):263-270. doi: 10.1111/jocd.12769. Epub 2018 Aug 26.

Helpful Links

• Topical silymarin versus hydroquinone in the treatment of melasma: A comparative study

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): December 31, 2019
• Study Completion (Actual): January 15, 2020

Study Registration Dates

• First Submitted: May 27, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 12, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: melasma; hydroquinone; silymarin
• Additional Relevant MeSH Terms: Skin Diseases; Hyperpigmentation; Pigmentation Disorders; Melanosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antioxidants; Radiation-Protective Agents; Hydroquinone; Silymarin
• Other Study ID Numbers: IMDC

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: No
• Studies a U.S. FDA-regulated device product: No