Comparison of Topical Silymarin With Hydroquinone in the Treatment of Melasma
Condition: Melasma
MeSH terms: Melanosis
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Hydroquinone 4% Cream; silymarin 0.7% cream
Intervention type(s): Drug; Drug
Intervention description(s): Hydroquinone is tyrosinase inhibitor and thus inhibits melanogenesis.; Silymarin is a plant derived flavonoid, extracted from fruits and seeds of milk thistle.
Intervention MeSH terms: Silymarin; Hydroquinone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: melasma; hydroquinone; silymarin