Potential Impact of Patient Vitamin D Status in AK Response to MAL-PDT

Study Overview
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Brief Summary
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In topical photodynamic therapy (PDT) for non-melanoma skin cancers, a photosensitizing prodrug, 5-aminolaevulinic acid (ALA) or its methylated ester, methyl aminolevulinate (MAL), is converted to the endogenous photosensitizer protoporphyrinIX (PpIX). Reduced response rates are observed in thicker skin lesions, which may be due to insufficient PpIX accumulation within the target tissue. To enhance PpIX production,several physical and chemical pretreatments have been suggested. One of the chemical substances proposed to stimulate PpIX production is vitamin D because of its ability of being a keratinocyte pro-differentiating hormone. Based on in vitro and in animal model studies, we propose to study the potential impact of patient vitamin D pre-treatment in AK response to MAL-PDT.

Detailed Description
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A randomized, controlled Split -scalp study with Calcipotriol Assisted MAL-PDT versus conventional MAL-PDT for actinic keratosis (AK) is proposed. Twenty patients ( male gender only) with symmetrically distributed multiple AK lesions on the scalp will be included. Patients must have at least five AKs per field to be eligible. After simple randomization, one half of the scalp will be treated with Calcipotriol ointment 50 mcg/g (Daivonex, Leo Pharma, Denmark) for 15 consecutive days. After this period, the entire scalp will be submitted to topical PDT with Methylaminolevulinate 16% (Metvix, Galderma France) under occlusion for 90 minutes and then, illuminated with a light source consisting of a Light Emitting Diode device (LED) at 635 nm ( Aktilite - Photocure, Norway). The total light dose will be 37J/cm2. Immediately before and after illumination with LED, measurements of the fluorescence intensity will be taken in 3 isolated spots in both sides of the scalp with a spectroscopy deviceUSB 2000+ ( Ocean Optics ® - Dunedin, Fl, USA). AK lesions will be counted and mapped by a dermatologist not involved in the study before and after 3 months. All patients will be advised to apply sunscreens 50 + 3x/day for the following 7 days after the procedure. A 0-10 Visual Analogue Scale (VAS) will be used to measure the pain intensity during the illumination. Records will be taken after 90 days and compared between sides: side effects, AK lesion response and pain level intensity. Also, a long term follow up will be provided at 6 and 12 months after.

Official Title
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Efficacy of Calcipotriol Assisted MAL-PDT Versus Conventional MAL-PDT for Actinic Keratosis: a Randomized and Controlled Study

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Other: Conventional MAL-PDT
* Other: Calcipotriol assisted MAL-PDT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male gender at least six AKs per field Exclusion Criteria: history of photosensitivity related disorders active infectious disease, immunosuppression laser or any cosmetic treatment in the previous 6 months other topical agents in the treatment area such as retinoids, 5-fluorouracil,imiquimod or diclofenac sodium in the previous 3 months allergy to MAL or excipients of the cream poor patient compliance.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Conventional MAL-PDT<br>Conventional topical PDT with Methylaminolevulinate 16% in one half of the scalp with multiple AKs. | Other: Conventional MAL-PDT<br>* Curettage of lesions and application of MAl cream 16% for 90 minutes under occlusion followed by LED 635 nm illumination at 37 J/cm2 total dose<br>|
| Other: Calcipotriol assisted MAL-PDT<br>Calcipotriol ointment 50 mcg/g applied once a day for 15 consecutive days in one half of the scalp, before Conventional topical PDT | Other: Calcipotriol assisted MAL-PDT<br>* Calcipotriol 50 mcg/g for 15 days prior to PDT. Curettage of lesions and application of MAl cream 16% for 90 minutes under occlusion followed by LED 635 nm illumination at 37 J/cm2 total dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes From Baseline in Actinic Keratosis - Lesion Base Count. | To compare the efficacy of topical PDT alone versus Calcipotriol assisted PDT for AKs on the scalp. The values in the data table represent the mean (+sd) number of lesions on each side at 3, 6 and 12 months post intervention. Lesion counts include lesions that have not been cleared and also newly emerged lesions ( if new lesions emerge on the treated field) At baseline: number of AKs was 290 on the CAL-PDT side and 284 on the conventional side. | Change from baseline, 90 days, 180 days and 12 months after the PDT | 
| Percentage of Actinic Keratosis (AK) Lesions Cleared | AK clearance after PDT and comparison between the sides The values in the data table represent the percentage of AK clearance on each side at 3, 6 and 12 months post intervention. At baseline: 290 on the CAL-PDT side and 284 on the conventional side. | Change from baseline, 90 days, 6 months and 12 months after PDT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Scores Immediately Post Illumination | Measurement of pain during LED illumination and comparison between the sides with a visual analogue scale (VAS), considering 0 as absence of pain and 10 as the most severe pain. At baseline, before the illumination, there is an absence of pain, which means Score 0 (zero) for all participants before the procedure. Pain is reffered during and after the illumination and measured with the VAS scale, reported by each patient. | immediately after intervention | 
| Change From Baseline in Fluorescence Intensity of PPIX | Measurement of PPIX fluorescence on both sides of the scalp before and immediately after LED illumination PpIX fluorescence was measured in three different spot areas on the scalp before and immediately after PDT on each side. The measurements were taken noninvasively in the areas where PpIX fluorescence was more intense, with a handheld fluorescence photometer (USB 2000+ spectroscopy device; Ocean Optics, Dunedin, FL, U.S.A.). The photometer illuminates a circular skin area with a diameter of 1 cm with blue light (400-420 nm), matching the Soret band of PpIX at 405-420 nm. By measuring excitation wavelengths at 600- 700 nm, the corresponding red PpIX fluorescence intensity at 633 nm is detected. Measurements were taken in arbitrary units. The mean PpIX fluorescence value for each side was calculated before and after the treatment. | Baseline and 10 minutes after illumination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PDT, skin cancer, calcipotriol