Efficacy of Topical Calcipotriol-assisted AFL-PDT in Actinic Keratosis
Condition: Actinic Dermatosis
MeSH terms: Keratosis, Actinic; Keratosis; Skin Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      Vitamin D(Vit D) is a pro-differentiation agent that enhances the accumulation of
      protoporphyrin IX (PpIX) after MAL(methyl-aminolevulinate) incubation in actinic keratosis
      and may have significant benefit for the treatment of actinic keratosis by ablative
      fractional laser-primed photodynamic therapy (AFL-PDT).
    

Detailed description: 
      Photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is effective in the treatment of
      actinic keratosis (AK). Many strategies have been studied to improve the production of
      protoporphyrin IX (PpIX), to improve efficacy of PDT. Pre-treatment of the skin with
      fractional laser resurfacing is a novel alternative technique to improve the efficacy of PDT
      for AK. The investigators' previous studies showed that ablative fractional laser primed PDT
      (AFL-PDT) offered higher efficacy than conventional MAL-PDT in the treatment of AK. But,
      reduced response rates are also observed in thicker skin lesions, which may be due to
      insufficient PpIX accumulation within the target tissue.

      Cellular differentiation leads to increased synthesis of PpIX from MAL and consecutively,
      differentiation therapy enhances photosensitization effect. Topical calcipotriol is a
      well-known pro-differentiation hormone and was demonstrated to influence the effect of PDT on
      keratinocytes.

      The aim of this study was to evaluate efficacy of topical vitamin D in AFL-PDT for AK
      treatment. Consequently, the investigator compared efficacy, recurrence rate, cosmetic
      outcome and safety between VitD - AFL-PDT and conventional AFL-PDT.
    

Intervention name(s): Topical Vitamin D (Calcipotriol) application; Placebo cream application; lidocaine/prilocaine (5%) application; 2940-nm Er:YAG AFL pretreatment; MAL application; Measurements of the fluorescence intensity; irradiation with red light-emitting diode lamp
Intervention type(s): Drug; Drug; Drug; Device; Drug; Other; Device
Intervention description(s): Calcipotriol ointment 50 mcg/g (Daivonex, Leo Pharma, Denmark) was applied twice for daily on treatment area for 15 consecutive days.; placebo cream (indistinguishable from calcipotriol cream by visual and physical appearance and sense of smell) was applied twice for daily on treatment area for 15 consecutive days.; For AFL pre-treatment, lidocaine/prilocaine (5%) cream (EMLA; Astra Pharmaceuticals, LP, Westborough, MA, USA) was applied to the treatment area under occlusion for 30 min; After the anaesthetic cream was removed, AFL therapy was performed using a 2940-nm Er:YAG AFL (Joule; Sciton Inc., Palo Alto, CA, USA) at 300-550 µm ablation depth, level 1 coagulation, 22% treatment density and a single pulse; 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. Incubation time is 3 hours; After 3 hours of application with MAL, saline wash was performed and fluorescence imaging analysis was performed with ultraviolet examination light (model 31602,356 nm; Burton Medical Products Crop.) at 10 cm height above the base of each lesion. The red fluorescence (610 nm-700 nm) was separated and extracted by ImageJ program and then used to measure the amount of 633 nm fluorescence of protoporphyrin IX.; 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 a total light dose of 37 J/cm-2. All patients wore protective goggles during illumination.
Intervention MeSH terms: Vitamin D; Lidocaine; Prilocaine; Lidocaine, Prilocaine Drug Combination; Calcipotriene
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Vitamin D; Calcipotriol; Ablative fractional laser; Actinic keratosis; Photodynamic therapy