<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/NCT02198469</url>
  </required_header>
  <id_info>
    <org_study_id>DAUderma-03</org_study_id>
    <nct_id>NCT02198469</nct_id>
  </id_info>
  <brief_title>Study of Methyl Aminolaevulinate Photodynamic Therapy With and Without Er:YAG Laser in Actinic Cheilitis</brief_title>
  <official_title>A Randomized, Prospective Study Comparing Methyl Aminolaevulinate Photodynamic Therapy With and Without Er:YAG Ablative Fractional Laser Treatment for Actinic Cheilitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dong-A University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dong-A University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is advantageous in that it has few&#xD;
      cosmetic side effects and minimises patient discomfort. However, its relatively low efficacy&#xD;
      prevents its application to the treatment of actinic cheilitis(AC). Er:YAG ablative&#xD;
      fractional laser (AFL) treatment removes the stratum corneum to increase MAL uptake and may&#xD;
      improve efficacy. However, no studies have directly compared the efficacy of MAL-PDT with and&#xD;
      without Er:YAG AFL in treating AC&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Actinic cheilitis (AC) is a keratinocytic neoplasm of the lip, especially the lower lip, is&#xD;
      confined to the epidermis, and results from chronic or excessive ultraviolet exposure. AC is&#xD;
      an early manifestation of lip squamous cell carcinoma (SCC), and SCC of the lip is usually&#xD;
      associated with an identifiable pre-existent AC. Furthermore, the likelihood that AC will&#xD;
      progress to SCC is higher than actinic keratosis (AK). Consequently, early identification and&#xD;
      treatment of AC is recommended. PDT involves the activation of a photosensitizer by&#xD;
      irradiation with 400- to 700-nm light to create cytotoxic oxygen and free radicals that kill&#xD;
      dysplastic cells.&#xD;
&#xD;
      Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is advantageous in that it has few&#xD;
      cosmetic side effects and minimises patient discomfort. However, its relatively low efficacy&#xD;
      prevents its application to the treatment of actinic cheilitis(AC).&#xD;
&#xD;
      Erbium:yttrium-aluminium-garnet (Er:YAG) ablative fractional laser (AFL) therapy has been&#xD;
      used frequently to improve treatment efficacy of PDT. Er:YAG AFL can ablate stratum corneum&#xD;
      with minimal penetration depth and producing minimal thermal injury. This approach creates&#xD;
      microscopic vertical holes in the ablated tissue, surrounded by thin layers of coagulated&#xD;
      tissue. Er:YAG AFL does not injure the entire thickness of the epidermis; therefore, healing&#xD;
      times are minimised. Erbium:yttrium-aluminium-garnet (Er:YAG) ablative fractional laser (AFL)&#xD;
      has been proven in recent studies to facilitate the delivery and uptake of topical MAL deep&#xD;
      into the skin, enhancing porphyrin synthesis and photodynamic activation.&#xD;
&#xD;
      The aim of our study was to compare efficacy, recurrence rate, cosmetic outcome, and safety&#xD;
      between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT in patients&#xD;
      with AC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference the efficacy between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT.</measure>
    <time_frame>Efficacy was evaluated at 3 months and 12 months after treatment</time_frame>
    <description>Lesion response was classified as either complete (complete disappearance of the lesion) or incomplete (incomplete disappearance) on the basis of visual examination and palpation. The response of each lesion was clinically evaluated</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference of the cosmetic outcomes between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT.</measure>
    <time_frame>Cosmetic outcome was assessed by each investigator for all lesions that achieved a complete response at 12 months</time_frame>
    <description>It was graded using a 4-point scale: excellent (only slight occurrence of redness or change in pigmentation), good (moderate redness or change in pigmentation), fair (slight-to-moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Difference of the recurrence rates and safety between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT</measure>
    <time_frame>within 12 months after both treatment</time_frame>
    <description>If the case of complete response of lesions, all patients were reviewed at 12 months to check recurrence.&#xD;
Adverse events reported by the patient were noted at each follow-up visit, including severity, duration, and need for additional therapy. All events due to PDT were described as phototoxic reactions(e.g. erythema, burning sensation, swelling, bleeding)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Actinic Cheilitis</condition>
  <arm_group>
    <arm_group_label>Er:YAG AFL-PDT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eligible patients were successively randomised to receive treatment with a single session of Er:YAG AFL MAL-PDT or 2 sessions of MAL-PDT with a 1-week interval between sessions</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MAL-PDT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Eligible patients were successively randomised to receive treatment with a single session of Er:YAG AFL MAL-PDT or 2 sessions of MAL-PDT with a 1-week interval between sessions</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Er:YAG AFL-PDT</intervention_name>
    <description>Er:YAG AFL was performed with 350 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. MAL cream was then applied under occlusion for 3 hrs and illuminated with a red light-emitting diode light at 37 J/cm2.</description>
    <arm_group_label>Er:YAG AFL-PDT</arm_group_label>
    <other_name>Er:YAG ablative fractional laser-assisted MAL-PDT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MAL-PDT</intervention_name>
    <description>a 1-mm thick layer of MAL (16% Metvix® cream, PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, Saint Paul, MN, US) for 3 hours, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light. Each treatment area was then separately illuminated with red light-emitting diode (LED) lamps (Aktilite CL128; Galderma, Bruchsal, Germany) with peak emission at 632 nm and total light dose of 37 J cm-2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later.</description>
    <arm_group_label>MAL-PDT</arm_group_label>
    <other_name>methyl aminolaevulinate-Photodynamic therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Korean patients ≥ 18 years of age who had biopsy-confirmed AC lesions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  porphyria&#xD;
&#xD;
          -  known allergies to the MAL cream or lidocaine&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  lactation&#xD;
&#xD;
          -  any active systemic infectious disease&#xD;
&#xD;
          -  immunosuppressive treatment&#xD;
&#xD;
          -  personal history of malignant melanoma&#xD;
&#xD;
          -  tendency towards melasma or keloid formation&#xD;
&#xD;
          -  prior treatment of the lesions within 4 weeks&#xD;
&#xD;
          -  any indication of poor compliance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>92 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Dong-A University</name>
      <address>
        <city>Busan</city>
        <state>Dong dae sin-dong, Seo-gu</state>
        <zip>602-715</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 23, 2014</study_first_posted>
  <last_update_submitted>July 22, 2014</last_update_submitted>
  <last_update_submitted_qc>July 22, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 23, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dong-A University</investigator_affiliation>
    <investigator_full_name>Song Ki-Hoon</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>actinic cheilitis</keyword>
  <keyword>Er:YAG ablative fractional laser</keyword>
  <keyword>methyl aminolevulinate photodynamic therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cheilitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methyl 5-aminolevulinate</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/NCT02198469
org study id: DAUderma-03
nct id: NCT02198469
lead sponsor: 
has dmc: No
Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is advantageous in that it has few
      cosmetic side effects and minimises patient discomfort. However, its relatively low efficacy
      prevents its application to the treatment of actinic cheilitis(AC). Er:YAG ablative
      fractional laser (AFL) treatment removes the stratum corneum to increase MAL uptake and may
      improve efficacy. However, no studies have directly compared the efficacy of MAL-PDT with and
      without Er:YAG AFL in treating AC
Actinic cheilitis (AC) is a keratinocytic neoplasm of the lip, especially the lower lip, is
      confined to the epidermis, and results from chronic or excessive ultraviolet exposure. AC is
      an early manifestation of lip squamous cell carcinoma (SCC), and SCC of the lip is usually
      associated with an identifiable pre-existent AC. Furthermore, the likelihood that AC will
      progress to SCC is higher than actinic keratosis (AK). Consequently, early identification and
      treatment of AC is recommended. PDT involves the activation of a photosensitizer by
      irradiation with 400- to 700-nm light to create cytotoxic oxygen and free radicals that kill
      dysplastic cells.

      Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is advantageous in that it has few
      cosmetic side effects and minimises patient discomfort. However, its relatively low efficacy
      prevents its application to the treatment of actinic cheilitis(AC).

      Erbium:yttrium-aluminium-garnet (Er:YAG) ablative fractional laser (AFL) therapy has been
      used frequently to improve treatment efficacy of PDT. Er:YAG AFL can ablate stratum corneum
      with minimal penetration depth and producing minimal thermal injury. This approach creates
      microscopic vertical holes in the ablated tissue, surrounded by thin layers of coagulated
      tissue. Er:YAG AFL does not injure the entire thickness of the epidermis; therefore, healing
      times are minimised. Erbium:yttrium-aluminium-garnet (Er:YAG) ablative fractional laser (AFL)
      has been proven in recent studies to facilitate the delivery and uptake of topical MAL deep
      into the skin, enhancing porphyrin synthesis and photodynamic activation.

      The aim of our study was to compare efficacy, recurrence rate, cosmetic outcome, and safety
      between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT in patients
      with AC.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Difference the efficacy between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT.
time frame: Efficacy was evaluated at 3 months and 12 months after treatment
description: Lesion response was classified as either complete (complete disappearance of the lesion) or incomplete (incomplete disappearance) on the basis of visual examination and palpation. The response of each lesion was clinically evaluated
measure: Difference of the cosmetic outcomes between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT.
time frame: Cosmetic outcome was assessed by each investigator for all lesions that achieved a complete response at 12 months
description: It was graded using a 4-point scale: excellent (only slight occurrence of redness or change in pigmentation), good (moderate redness or change in pigmentation), fair (slight-to-moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration)
measure: Difference of the recurrence rates and safety between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL MAL-PDT) and standard MAL-PDT
time frame: within 12 months after both treatment
description: If the case of complete response of lesions, all patients were reviewed at 12 months to check recurrence.
Adverse events reported by the patient were noted at each follow-up visit, including severity, duration, and need for additional therapy. All events due to PDT were described as phototoxic reactions(e.g. erythema, burning sensation, swelling, bleeding)
arm group label: Er:YAG AFL-PDT
arm group type: Experimental
description: Eligible patients were successively randomised to receive treatment with a single session of Er:YAG AFL MAL-PDT or 2 sessions of MAL-PDT with a 1-week interval between sessions
arm group label: MAL-PDT
arm group type: Active Comparator
description: Eligible patients were successively randomised to receive treatment with a single session of Er:YAG AFL MAL-PDT or 2 sessions of MAL-PDT with a 1-week interval between sessions
intervention type: Drug
intervention name: Er:YAG AFL-PDT
description: Er:YAG AFL was performed with 350 µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. MAL cream was then applied under occlusion for 3 hrs and illuminated with a red light-emitting diode light at 37 J/cm2.
arm group label: Er:YAG AFL-PDT
other name: Er:YAG ablative fractional laser-assisted MAL-PDT
intervention type: Drug
intervention name: MAL-PDT
description: a 1-mm thick layer of MAL (16% Metvix® cream, PhotoCure ASA, Oslo, Norway) was applied to the lesion and to 5 mm of surrounding healthy tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, Saint Paul, MN, US) for 3 hours, after which the remaining cream was removed with saline gauze, and the red fluorescence of porphyrins was visualized with Wood's light. Each treatment area was then separately illuminated with red light-emitting diode (LED) lamps (Aktilite CL128; Galderma, Bruchsal, Germany) with peak emission at 632 nm and total light dose of 37 J cm-2. Areas scheduled to receive MAL-PDT received the second treatment 7 days later.
arm group label: MAL-PDT
other name: methyl aminolaevulinate-Photodynamic therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 92 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Dong-A University
investigator full name: Song Ki-Hoon
investigator title: Associate Professor
mesh term: Cheilitis
mesh term: Methyl 5-aminolevulinate