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NCT Number: NCT02976727

Efficacy of Topical Calcipotriol-assisted AFL-PDT in Actinic Keratosis

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).

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Key information

Conditions

Actinic Dermatosis Keratosis Keratosis, Actinic Neoplasms Precancerous Conditions Skin Diseases Skin and Connective Tissue Diseases

Age range

65 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Dong-A University

Busan, Seo-gu, Korea, Republic Of, 602-715, South Korea

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Korean patients aged ≥ 18 years who had biopsy-confirmed Actinic keratosis lesions

Exclusion criteria

  • calcium metabolic disorder patients
  • photosensitivity disorder patients
  • lactating or pregnant women
  • patients with porphyria or a known allergy to any of the constituents of the MAL cream and lidocaine
  • patients with systemic disease, history of malignant melanoma, tendency of melasma development or keloid formation, any AK treatment of the area in the previous 4 weeks, or any conditions associated with a risk of poor protocol compliance; and patients on immunosuppressive treatment

Treatment and study plan

Topical Vitamin D (Calcipotriol) application

Drug

Calcipotriol ointment 50 mcg/g (Daivonex, Leo Pharma, Denmark) was applied twice for daily on treatment area for 15 consecutive days.

Placebo cream application

Drug

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.

lidocaine/prilocaine (5%) application

Drug

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

2940-nm Er:YAG AFL pretreatment

Device

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

MAL application

Drug

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

Measurements of the fluorescence intensity

Other

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.

irradiation with red light-emitting diode lamp

Device

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.

Primary outcomes

  1. Differences of short-term complete response rates between VitD-AFL-PDT and AFL-PDT

    Time frame: Short-term complete response rates were evaluated at 3 months after treatment

    Lesion responses were classified as either a complete response (complete disappearance of the lesion) or a noncomplete response (incomplete disappearance)

  2. Differences of long-term complete response rates between VitD-AFL-PDT and AFL-PDT

    Time frame: Long-term complete response rates were evaluated at 12 months

    In all cases of complete response, the patients were reviewed at 12 months to check for recurrence. Recurrence was assessed by inspection, dermoscopy, photography, palpation, and histologic findings. For the histopathologic evaluation of treatment response, at the 12-month follow-up visit, a 3-mm punch biopsy of the treated AK lesion was performed in all cases of clinically incomplete response.

  3. Difference of the recurrence rates between VitD-AFL-PDT and AFL-PDT

    Time frame: Recurrence rates were evaluated respectively at 12 months after treatment.

    In all cases of complete response, the patients were reviewed at 12 months to check for recurrence. Recurrence was assessed by inspection, dermoscopy, photography, palpation, and histologic findings. For the histopathologic evaluation of treatment response, at the 12-month follow-up visit, a 3-mm punch biopsy of the treated AK lesion was performed in all cases of clinically incomplete response.

Secondary outcomes

  1. Differences of cosmetic outcomes between VitD-AFL-PDT and AFL-PDT

    Time frame: The overall cosmetic outcome was assessed 12 months after treatment

    Cosmetic outcomes were 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)

  2. Difference of adverse events (erythema, post-inflammatory hyperpigmentation, edema, itching, oozing, bleeding) rates between VitD-AFL-PDT and AFL-PDT

    Time frame: Within 12 months after each treatment

    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 (i.e., erythema, post-inflammatory hyperpigmentation, oedema, itching, oozing, bleeding and so forth).

Other outcomes

  1. Differences of the fluorescence intensity between VitD-AFL-PDT and AFL-PDT

    Time frame: After 3 hours of application with MAL, fluorescence intensity imaging was assessed 10 minutes before illumination.

    After 3 hours of application with MAL, Fluorescence imaging analysis was performed on treatment area 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 was separated and extracted by ImageJ program and then used to measure the amount of 633 nm fluorescence of protoporphyrin IX.

Sponsors and collaborators

Lead sponsor

Dong-A University

Other

Registry information

Official study title

Efficacy of Topical Calcipotriol-assisted Ablative Fractional Laser Photodynamic Therapy for the Treatment of Actinic Keratosis: 12-month Follow-up Results of a Prospective, Randomised, Comparative Trial

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Nov 29, 2016
Registry last updated
Nov 29, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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