Daylight-mediated Photodynamic Therapy of Actinic Keratoses:Comparing 0.2%HAL With 16%MAL

Study Overview
=================
Brief Summary
-----------------
This pilot study compares two photosensitizers, hexylaminolaevulinate (HAL) and methylaminolaevulinate (MAL), in treatment of actinic keratoses. Study is conducted using randomized split-face design. Efficacy is assessed clinically, and histologically at 3 and 12 months. Pain during and after treatments and adverse reactions at one week are recorded.

Detailed Description
-----------------
Study recruites 16-20 voluuntering patients with symmetrical actinic damage on face or scalp. Treatment sites are randomized to receive either hexylaminolaevulinate 0.2% or methylaminolaevulinate ( 16% MAL) as photosensitizers (0.25mm-thick layer). A web-based validated program (Research Randomizer) generated a randomized list to define the treatment sides. The randomization results were kept blinded from the investigators who conducted the follow-up visits, from the pathologist, and the patients. Pre-treatment procedures include application of sunscreen for 15 minutes and curettage of the treatment area. Illumination is performed using 2 hours daylight-exposure. Efficacy is assessed clinically, and histologically at 3 and 12 months by blinded observers. Pain during and after treatments and adverse reactions at one week are recorded.

Official Title
-----------------
Daylight-mediated Photodynamic Therapy of Actinic Keratoses: a Randomized, Double-blinded Pilot Study Comparing Topical 0.2% Hexylaminolaevulinate With 16% Methylaminolaevulinate

Conditions
-----------------
Actinic Keratoses

Intervention / Treatment
-----------------
* Drug: Hexylaminolaevulinate cream
* Drug: Methylaminolaevulinate cream


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: -Symmetrical actinic damage on face or scalp Exclusion Criteria: Pregnancy Lactation Allergy to photosensitizer Photodermatose

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAL cream and MAL cream<br>0.2% HAL (Hexvix, Photocure) mixed with Unguentum M (Allmiral) and MAL (Metvix, Galderma) used in a randomized split-face design | Drug: Hexylaminolaevulinate cream<br>* 0.2% Hexylaminolaevulinate (Hexvix, Photocure) mixed with Unguentum M (Allmiral) cream (2014)<br>* Other names: Hexvix, Photocure;Drug: Methylaminolaevulinate cream<br>* MAL 16% is used as photosensitizer for daylight-PDT<br>* Other names: MAL;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Histological Lesion Clearance | Punch biopsies were taken symmetrically on both treatment fields from equally graded >6 mm AKs prior to treatment and again at 3 months, blinded observer (pathologist). HE- and p53-stainings. Samples not fulfilling the criteria of an AK were defined as healthy or completely cleared. The p53 reactivity expressed as average percentage of positive nuclei in three consecutive high power fields from the region of highest reactivity (<10 % normal) | Baseline, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Lesion Clearance | Clinical lesion clearance is observed by a blinded observer | Baseline, 3 months | 
| Adverse Reactions | Adverse reactions are evaluated by blinded observer at one week after treatment. Severity of the reaction ( Redness, crusting and scaling) is assessed using grading: minimal, mild, intermediate, severe. | One week | 
| Pain Assesment (Visual Analog Scale) | Pain using visual analog scale (VAS 0-10, where 0 is no pain and 10 is the worst pain imaginable) on both treatment sides is assessed in every 30 minutes during 2-hour sun-exposure and afterwards once in two hours until 9 p.m. (treatment day). Of these values, the mean maximal pain is assessed. | 12 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MAL, Actinic keratoses, Daylight-PDT, Hexylaminolaevulinate, HAL, Methylaminolaevulinate, Hyperspectral imaging