<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/NCT02248298</url>
  </required_header>
  <id_info>
    <org_study_id>DAUderma-04</org_study_id>
    <nct_id>NCT02248298</nct_id>
  </id_info>
  <brief_title>Efficacy of AFL-assisted PDT With Short Incubation Time in Actinic Keratosis</brief_title>
  <official_title>Efficacy of Ablative Fractional Laser-assisted Photodynamic Therapy With Short Incubation Time for the Treatment of Facial and Scalp Actinic Keratosis: 12-month Follow-up Results of a Randomized, Prospective, Comparative Trial</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>
      Photodynamic therapy (PDT) using methyl aminolevulinate (MAL) is an effective first-line&#xD;
      treatment for actinic keratosis (AK). Erbium: yttrium-aluminium-garnet (Er:YAG) ablative&#xD;
      fractional laser-assisted MAL-PDT (AFL-PDT) has shown significant benefit for the treatment&#xD;
      of AK. However, knowledge on the optimal photosensitizer incubation time for AFL-PDT is&#xD;
      limited&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Photodynamic therapy (PDT) is widely used in the treatment of superficial skin cancer. It has&#xD;
      an excellent cosmetic outcome, and it could be considered the first-line therapy for Actinic&#xD;
      keratosis (AK). In PDT incubation time is required so that the photosensitizer can be&#xD;
      converted to PpIX. The recommended treatment regimen of PDT requires a relatively long&#xD;
      incubation time with ALA (4 hours) and MAL (3 hours) before illumination. Theoretically,&#xD;
      ablative fractional laser (AFL) pre-treatment may facilitate the penetration and distribution&#xD;
      of topically applied drugs, since the ablated laser holes extend into the dermis, thereby&#xD;
      possibly acting as channels for drug uptake. However, knowledge on the optimal&#xD;
      photosensitizer incubation time for AFL-PDT is limited. The objectives of this study were to&#xD;
      compare the efficacy, recurrence rate, cosmetic outcome, and safety between AFL-PDT with 2&#xD;
      and 3hours of incubation vs. conventional MAL-PDT in patients with facial and scalp AK.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 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 of the efficacy between 3h-AFL-PDT, 2hr-AFL-PDT and 3h-MAL-PDT</measure>
    <time_frame>Efficacy was evaluated at 3 months and 12 months after treatment</time_frame>
    <description>The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference of the cosmetic outcome between 3h-AFL-PDT, 2hr-AFL-PDT and 3h-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 as excellent (slight redness or pigmentation change), good (moderate redness or pigmentation change), 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 3h-AFL-PDT, 2hr-AFL-PDT and 3h-MAL-PDT</measure>
    <time_frame>within 12 months after each 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>3</number_of_arms>
  <enrollment type="Actual">93</enrollment>
  <condition>Actinic Keratosis</condition>
  <arm_group>
    <arm_group_label>2h-AFL-PDT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3hr-AFL-PDT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3hr-MAL-PDT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>2h-AFL-PDT</intervention_name>
    <description>AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. In the 3h-MAL-PDT group, the above mentioned procedures were not performed. Immediately after AFL treatment, an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 2 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2</description>
    <arm_group_label>2h-AFL-PDT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>3h-AFL-PDT</intervention_name>
    <description>AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. In the 3h-MAL-PDT group, the above mentioned procedures were not performed. Immediately after AFL treatment, an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2</description>
    <arm_group_label>3hr-AFL-PDT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>3hr-MAL-PDT</intervention_name>
    <description>an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2.</description>
    <arm_group_label>3hr-MAL-PDT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age &gt;18 years&#xD;
&#xD;
          -  the presence of 2-10 facial AK lesions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  lactating or pregnant women&#xD;
&#xD;
          -  patients with porphyria&#xD;
&#xD;
          -  a known allergy to any of the constituents of the MAL cream and lidocaine&#xD;
&#xD;
          -  patients with systemic disease&#xD;
&#xD;
          -  history of malignant melanoma&#xD;
&#xD;
          -  tendency for melasma development or keloid formation&#xD;
&#xD;
          -  any AK treatment of the area in the previous 4 weeks&#xD;
&#xD;
          -  any conditions associated with a risk of poor protocol compliance&#xD;
&#xD;
          -  patients on immunosuppressive treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>87 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>September 2014</verification_date>
  <study_first_submitted>September 20, 2014</study_first_submitted>
  <study_first_submitted_qc>September 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>September 20, 2014</last_update_submitted>
  <last_update_submitted_qc>September 20, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 25, 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>Ablative fractional laser</keyword>
  <keyword>Actinic keratosis</keyword>
  <keyword>Efficacy</keyword>
  <keyword>Photodynamic therapy</keyword>
  <keyword>Short incubation time</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratosis, Actinic</mesh_term>
    <mesh_term>Keratosis</mesh_term>
  </condition_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/NCT02248298
org study id: DAUderma-04
nct id: NCT02248298
lead sponsor: 
has dmc: No
Photodynamic therapy (PDT) using methyl aminolevulinate (MAL) is an effective first-line
      treatment for actinic keratosis (AK). Erbium: yttrium-aluminium-garnet (Er:YAG) ablative
      fractional laser-assisted MAL-PDT (AFL-PDT) has shown significant benefit for the treatment
      of AK. However, knowledge on the optimal photosensitizer incubation time for AFL-PDT is
      limited
Photodynamic therapy (PDT) is widely used in the treatment of superficial skin cancer. It has
      an excellent cosmetic outcome, and it could be considered the first-line therapy for Actinic
      keratosis (AK). In PDT incubation time is required so that the photosensitizer can be
      converted to PpIX. The recommended treatment regimen of PDT requires a relatively long
      incubation time with ALA (4 hours) and MAL (3 hours) before illumination. Theoretically,
      ablative fractional laser (AFL) pre-treatment may facilitate the penetration and distribution
      of topically applied drugs, since the ablated laser holes extend into the dermis, thereby
      possibly acting as channels for drug uptake. However, knowledge on the optimal
      photosensitizer incubation time for AFL-PDT is limited. The objectives of this study were to
      compare the efficacy, recurrence rate, cosmetic outcome, and safety between AFL-PDT with 2
      and 3hours of incubation vs. conventional MAL-PDT in patients with facial and scalp AK.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Difference of the efficacy between 3h-AFL-PDT, 2hr-AFL-PDT and 3h-MAL-PDT
time frame: Efficacy was evaluated at 3 months and 12 months after treatment
description: The response was classified as either complete response (complete disappearance of the lesion) or incomplete response (incomplete disappearance of the lesion)
measure: Difference of the cosmetic outcome between 3h-AFL-PDT, 2hr-AFL-PDT and 3h-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 as excellent (slight redness or pigmentation change), good (moderate redness or pigmentation change), fair (slight-to-moderate scarring, atrophy, or induration), or poor (extensive scarring, atrophy, or induration).
measure: Difference of the recurrence rates and safety between 3h-AFL-PDT, 2hr-AFL-PDT and 3h-MAL-PDT
time frame: within 12 months after each 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: 2h-AFL-PDT
arm group type: Experimental
description: All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program.
arm group label: 3hr-AFL-PDT
arm group type: Active Comparator
description: All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program.
arm group label: 3hr-MAL-PDT
arm group type: Active Comparator
description: All 440 AK lesions of the 93 patients were randomly assigned to treatment with MAL-PDT (3h-MAL-PDT) or AFL-PDT with 2 hours (2h-AFL-PDT) and 3 hours (3h-AFL-PDT) of incubation time, using restricted randomization, with a computer-generated program.
intervention type: Drug
intervention name: 2h-AFL-PDT
description: AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. In the 3h-MAL-PDT group, the above mentioned procedures were not performed. Immediately after AFL treatment, an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 2 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2
arm group label: 2h-AFL-PDT
intervention type: Drug
intervention name: 3h-AFL-PDT
description: AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550µm ablation depth, level 1 coagulation, 22% treatment density, and a single pulse. In the 3h-MAL-PDT group, the above mentioned procedures were not performed. Immediately after AFL treatment, an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2
arm group label: 3hr-AFL-PDT
intervention type: Drug
intervention name: 3hr-MAL-PDT
description: an approximately 1-mm thick layer of MAL (Metvix, PhotoCure ASA, Oslo, Norway) was applied to the lesion and on 5 mm of surrounding normal tissue. The area was covered with an occlusive dressing (Tegaderm, 3M, St. Paul, MN, USA). After incubation for 3 hours, the dressing and cream were removed, and the area was cleansed with saline. The area was irradiated with a red light-emitting diode lamp (Aktilite CL 128; PhotoCure ASA, Oslo, Norway) with peak emission at 632 nm, placed 5 cm away from the skin surface and total light dose of 37 J/cm-2.
arm group label: 3hr-MAL-PDT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 87 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: Keratosis, Actinic
mesh term: Keratosis