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

Actinic Dermatosis Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02976727
• Other study ID #: DAUderma-07
• Status: Completed
• Phase: Phase 1
• First received: November 5, 2016
• Last updated: November 28, 2016
• Start date: May 2014
• Est. completion date: August 2015

Study information

• Verified date: November 2016
• Source: Dong-A University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 65 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Actinic Dermatosis
• Keratosis
• Keratosis, Actinic
• Skin Diseases

Intervention

Drug:
• Topical Vitamin D (Calcipotriol) application
Calcipotriol ointment 50 mcg/g (Daivonex, Leo Pharma, Denmark) was applied twice for daily on treatment area for 15 consecutive days.
• Placebo cream application
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
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

Device:
• 2940-nm Er:YAG AFL pretreatment
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

Drug:
• MAL application
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

Other:
• Measurements of the fluorescence intensity
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.

Device:
• irradiation with red light-emitting diode lamp
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.

Locations

Country	Name	City	State
Korea, Republic of	Dong-A University	Busan, Seo-gu, Korea, Republic of, 602-715

Sponsors (1)

Lead Sponsor	Collaborator
Dong-A University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Differences of the fluorescence intensity between VitD-AFL-PDT and AFL-PDT	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.	After 3 hours of application with MAL, fluorescence intensity imaging was assessed 10 minutes before illumination.	No
Primary	Differences of short-term complete response rates between VitD-AFL-PDT and AFL-PDT	Lesion responses were classified as either a complete response (complete disappearance of the lesion) or a noncomplete response (incomplete disappearance)	Short-term complete response rates were evaluated at 3 months after treatment	No
Primary	Differences of long-term complete response rates between VitD-AFL-PDT and AFL-PDT	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.	Long-term complete response rates were evaluated at 12 months	No
Primary	Difference of the recurrence rates between VitD-AFL-PDT and AFL-PDT	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.	Recurrence rates were evaluated respectively at 12 months after treatment.	No
Secondary	Differences of cosmetic outcomes between VitD-AFL-PDT and AFL-PDT	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)	The overall cosmetic outcome was assessed 12 months after treatment	No
Secondary	Difference of adverse events (erythema, post-inflammatory hyperpigmentation, edema, itching, oozing, bleeding) rates between VitD-AFL-PDT and AFL-PDT	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).	Within 12 months after each treatment	No