<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01661556</url>
  </required_header>
  <id_info>
    <org_study_id>MICHQ</org_study_id>
    <nct_id>NCT01661556</nct_id>
  </id_info>
  <brief_title>Clinical Trial of Hydroquinone Versus Miconazol in Melasma</brief_title>
  <official_title>Double Blind Randomized Study of 2% Miconazol Versus 4% Hydroquinone in the Treatment for Melasma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidad Autonoma de San Luis Potosí</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital Central &quot;Dr. Ignacio Morones Prieto&quot;</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidad Autonoma de San Luis Potosí</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Melasma is an acquired discoloration of the skin characterized by brown colour changes&#xD;
      commonly on the face.The duration of this double-blind clinical trial will be 12 weeks. The&#xD;
      control group will receive treatment with topical Hydroquinone (4%), and the other group&#xD;
      topical miconazole. Miconazol has antimelanotic properties and can be used as treatment for&#xD;
      melasma patients. The estimated number of subjects to be recruited and randomized for the&#xD;
      study is at least 30. The purpose of this study is determine if there is a difference in the&#xD;
      effectiveness of these two agents. Melasma Area and Severity Index (MASI) score will be&#xD;
      assessed at the beginning of the study and at weeks 4, 8, and 12. Photographs, colorimetry&#xD;
      and histological assessment will be also evaluated. Occurrence of adverse effects will also&#xD;
      be recorded.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Melasma is a common acquired hypermelanosis in dark skin populations, usually characterized&#xD;
      by symmetrical, irregular macules occurring in photo-exposed areas such as face. Treatment&#xD;
      with depigmenting compounds such as hydroquinone, are still the gold standard in this&#xD;
      condition. Miconazol has depigmented properties that could be used as part of the treatment&#xD;
      in melasma patients. This effect is exerted by inhibiting the tyrosinase enzyme. So, the&#xD;
      primary objective of this study is to compare the depigmenting activity of miconazole against&#xD;
      hydroquinone.&#xD;
&#xD;
      Patients who are included in the study will be randomly assigned to receive one of the&#xD;
      treatments, which should use for 12 weeks. The medications should be applied in the affected&#xD;
      regions twice a day.&#xD;
&#xD;
      The evaluation of clinical improvement will be done in a blinded modality by means of the&#xD;
      MASI score, the Global Physician Assessment, as well as colorimetry and histological melanin&#xD;
      content. Evaluations will be held on visits at 4, 8 and 12 weeks. Skin biopsy will be taken&#xD;
      at onset and at 12 weeks.&#xD;
&#xD;
      At the end of the study, data will be compared concerning the former parameters. All side&#xD;
      effects will be recorded and analysed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2011</start_date>
  <completion_date type="Anticipated">December 2015</completion_date>
  <primary_completion_date type="Anticipated">February 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Depigmentation of melasma lesions by Colorimetry</measure>
    <time_frame>12 weeks</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Global Physician Assessment</measure>
    <time_frame>12 weeks</time_frame>
    <description>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 (&gt;75%).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MASI (Melasma Area Severity Index)</measure>
    <time_frame>12 weeks</time_frame>
    <description>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=&lt;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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Melanin content by Fontana Masson stain</measure>
    <time_frame>12 weeks</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Melasma</condition>
  <arm_group>
    <arm_group_label>Miconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>OTC topical prescription used for fungal treatment that can be useful to the treatment of melasma due to its depigmenting properties.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hydroquinone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Moisturizer cream without pharmacological effects will be used as a control.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Miconazole</intervention_name>
    <description>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.</description>
    <arm_group_label>Miconazole</arm_group_label>
    <other_name>Canesten</other_name>
    <other_name>Monistat</other_name>
    <other_name>Micatin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroquinone</intervention_name>
    <description>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.</description>
    <arm_group_label>Hydroquinone</arm_group_label>
    <other_name>Eldoquin</other_name>
    <other_name>Melanex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  Mexican women over 18 years of age&#xD;
&#xD;
          -  Dermatologic diagnostic of melasma&#xD;
&#xD;
          -  Phototype III or more&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
          -  Postbirth, abortion in the past 6 months&#xD;
&#xD;
          -  Having an endocrine or autoimmune disease&#xD;
&#xD;
          -  Under hormonal therapy of any kind including contraceptives or it´s use in the past 6&#xD;
             months&#xD;
&#xD;
          -  Currently under treatment for melasma including sunblock&#xD;
&#xD;
          -  Currently under radiation therapy, chemotherapy, immunosuppressants of any kind or&#xD;
             phototherapy or it´s use in the past 6 months&#xD;
&#xD;
          -  Having used or are consuming photosensitizing substances, oral or topical&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juan P Castanedo-Cazares, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Hospital Central &quot;Dr. Ignacio Morones Prieto&quot;. UASLP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Amalia Reyes-Herrera, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Central &quot;Dr. Ignacio Morones Prieto&quot;. UASLP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bertha Torres-Alvarez, M.D.</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Central &quot;Dr. Ignacio Morones Prieto&quot;. UASLP</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Amalia Reyes-Herrera, M.D.</last_name>
    <phone>52014448342795</phone>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Juan P Castanedo-Cazares, M.D.</last_name>
    <phone>52014448342795</phone>
    <email>castanju@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Dermatology Department. Hospital Central &quot;Dr. Ignacio Morones Prieto&quot;</name>
      <address>
        <city>San Luis Potosí</city>
        <zip>78210</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Juan Pablo Castanedo-Cazares, M.D.</last_name>
      <phone>52014448342795</phone>
      <email>castanju@yahoo.com</email>
    </contact>
    <contact_backup>
      <last_name>Bertha Torres-Alvarez, M.D.</last_name>
      <phone>52014448342795</phone>
      <email>torresmab@yahoo.com.mx</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <reference>
    <citation>Navarrete-Solis J, Castanedo-Cazares JP, Torres-Alvarez B, Oros-Ovalle C, Fuentes-Ahumada C, Gonzalez FJ, Martinez-Ramirez JD, Moncada B. A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma. Dermatol Res Pract. 2011;2011:379173. doi: 10.1155/2011/379173. Epub 2011 Jul 21.</citation>
    <PMID>21822427</PMID>
  </reference>
  <reference>
    <citation>Torres-Alvarez B, Mesa-Garza IG, Castanedo-Cazares JP, Fuentes-Ahumada C, Oros-Ovalle C, Navarrete-Solis J, Moncada B. Histochemical and immunohistochemical study in melasma: evidence of damage in the basal membrane. Am J Dermatopathol. 2011 May;33(3):291-5. doi: 10.1097/DAD.0b013e3181ef2d45.</citation>
    <PMID>21317614</PMID>
  </reference>
  <reference>
    <citation>Moncada B, Sahagun-Sanchez LK, Torres-Alvarez B, Castanedo-Cazares JP, Martinez-Ramirez JD, Gonzalez FJ. Molecular structure and concentration of melanin in the stratum corneum of patients with melasma. Photodermatol Photoimmunol Photomed. 2009 Jun;25(3):159-60. doi: 10.1111/j.1600-0781.2009.00425.x.</citation>
    <PMID>19438997</PMID>
  </reference>
  <reference>
    <citation>Hernandez-Barrera R, Torres-Alvarez B, Castanedo-Cazares JP, Oros-Ovalle C, Moncada B. Solar elastosis and presence of mast cells as key features in the pathogenesis of melasma. Clin Exp Dermatol. 2008 May;33(3):305-8. doi: 10.1111/j.1365-2230.2008.02724.x.</citation>
    <PMID>18419607</PMID>
  </reference>
  <reference>
    <citation>Espinal-Perez LE, Moncada B, Castanedo-Cazares JP. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J Dermatol. 2004 Aug;43(8):604-7. doi: 10.1111/j.1365-4632.2004.02134.x.</citation>
    <PMID>15304189</PMID>
  </reference>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>August 7, 2012</study_first_submitted>
  <study_first_submitted_qc>August 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <last_update_submitted>December 1, 2014</last_update_submitted>
  <last_update_submitted_qc>December 1, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 2, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidad Autonoma de San Luis Potosí</investigator_affiliation>
    <investigator_full_name>Juan Pablo Castanedo-Cazares</investigator_full_name>
    <investigator_title>Clinical Professor. Dermatology department.</investigator_title>
  </responsible_party>
  <keyword>Melasma, miconazole, hydroquinone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Miconazole</mesh_term>
    <mesh_term>Hydroquinone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01661556
org study id: MICHQ
nct id: NCT01661556
lead sponsor: 
collaborator: 
has dmc: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Depigmentation of melasma lesions by Colorimetry
time frame: 12 weeks
description: 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.
measure: Global Physician Assessment
time frame: 12 weeks
description: 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%).
measure: MASI (Melasma Area Severity Index)
time frame: 12 weeks
description: 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).
measure: Melanin content by Fontana Masson stain
time frame: 12 weeks
description: 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.
arm group label: Miconazole
arm group type: Experimental
description: OTC topical prescription used for fungal treatment that can be useful to the treatment of melasma due to its depigmenting properties.
arm group label: Hydroquinone
arm group type: Active Comparator
description: 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.
arm group label: Placebo
arm group type: Placebo Comparator
description: Moisturizer cream without pharmacological effects will be used as a control.
intervention type: Drug
intervention name: Miconazole
description: 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.
arm group label: Miconazole
other name: Canesten
other name: Monistat
other name: Micatin
intervention type: Drug
intervention name: Hydroquinone
description: 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.
arm group label: Hydroquinone
other name: Eldoquin
other name: Melanex
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Juan P Castanedo-Cazares, M.D.
role: Study Director
affiliation: Hospital Central "Dr. Ignacio Morones Prieto". UASLP
last name: Amalia Reyes-Herrera, M.D.
role: Principal Investigator
affiliation: Hospital Central "Dr. Ignacio Morones Prieto". UASLP
last name: Bertha Torres-Alvarez, M.D.
role: Study Chair
affiliation: Hospital Central "Dr. Ignacio Morones Prieto". UASLP
last name: Amalia Reyes-Herrera, M.D.
phone: 52014448342795
last name: Juan P Castanedo-Cazares, M.D.
phone: 52014448342795
email: castanju@yahoo.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Mexico
citation: Navarrete-Solis J, Castanedo-Cazares JP, Torres-Alvarez B, Oros-Ovalle C, Fuentes-Ahumada C, Gonzalez FJ, Martinez-Ramirez JD, Moncada B. A Double-Blind, Randomized Clinical Trial of Niacinamide 4% versus Hydroquinone 4% in the Treatment of Melasma. Dermatol Res Pract. 2011;2011:379173. doi: 10.1155/2011/379173. Epub 2011 Jul 21.
PMID: 21822427
citation: Torres-Alvarez B, Mesa-Garza IG, Castanedo-Cazares JP, Fuentes-Ahumada C, Oros-Ovalle C, Navarrete-Solis J, Moncada B. Histochemical and immunohistochemical study in melasma: evidence of damage in the basal membrane. Am J Dermatopathol. 2011 May;33(3):291-5. doi: 10.1097/DAD.0b013e3181ef2d45.
PMID: 21317614
citation: Moncada B, Sahagun-Sanchez LK, Torres-Alvarez B, Castanedo-Cazares JP, Martinez-Ramirez JD, Gonzalez FJ. Molecular structure and concentration of melanin in the stratum corneum of patients with melasma. Photodermatol Photoimmunol Photomed. 2009 Jun;25(3):159-60. doi: 10.1111/j.1600-0781.2009.00425.x.
PMID: 19438997
citation: Hernandez-Barrera R, Torres-Alvarez B, Castanedo-Cazares JP, Oros-Ovalle C, Moncada B. Solar elastosis and presence of mast cells as key features in the pathogenesis of melasma. Clin Exp Dermatol. 2008 May;33(3):305-8. doi: 10.1111/j.1365-2230.2008.02724.x.
PMID: 18419607
citation: Espinal-Perez LE, Moncada B, Castanedo-Cazares JP. A double-blind randomized trial of 5% ascorbic acid vs. 4% hydroquinone in melasma. Int J Dermatol. 2004 Aug;43(8):604-7. doi: 10.1111/j.1365-4632.2004.02134.x.
PMID: 15304189
responsible party type: Principal Investigator
investigator affiliation: Universidad Autonoma de San Luis Potosí
investigator full name: Juan Pablo Castanedo-Cazares
investigator title: Clinical Professor. Dermatology department.
mesh term: Melanosis
mesh term: Miconazole
mesh term: Hydroquinone