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

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

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.

Study Overview

• Status: Completed
• Conditions: Actinic Keratoses
• Intervention / Treatment: Drug: Hexylaminolaevulinate cream; Drug: Methylaminolaevulinate cream

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Finland
  • Lahti, Finland, 15850
    • Päijät-Häme Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-Symmetrical actinic damage on face or scalp

Exclusion Criteria:

• Pregnancy
• Lactation
• Allergy to photosensitizer
• Photodermatose

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance of Field Cancerization in Hyperspectral Images	Data not collected	3 months

Collaborators and Investigators

• Sponsor: Joint Authority for Päijät-Häme Social and Health Care
• Collaborators: Helsinki University Central Hospital
• Investigators: Principal Investigator: Noora E Neittaanmäki-Perttu, MD, Päijät-Häme Cnetral Hospital, Helsinki University Central Hospital; Study Director: Mari Grönroos, MD, PhD, Päijät-Häme Central Hospital

Publications and helpful links

General Publications

• Neittaanmaki-Perttu N, Gronroos M, Karppinen TT, Tani TT, Snellman E. Hexyl-5-aminolaevulinate 0.2% vs. methyl-5-aminolaevulinate 16% daylight photodynamic therapy for treatment of actinic keratoses: results of a randomized double-blinded pilot trial. Br J Dermatol. 2016 Feb;174(2):427-9. doi: 10.1111/bjd.13924. Epub 2015 Nov 20. No abstract available.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: May 19, 2014
• First Submitted That Met QC Criteria: May 25, 2014
• First Posted (Estimate): May 29, 2014

Study Record Updates

• Last Update Posted (Estimate): July 11, 2016
• Last Update Submitted That Met QC Criteria: May 29, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Hyperspectral imaging; Actinic keratoses; HAL; Daylight-PDT; Hexylaminolaevulinate; Methylaminolaevulinate; MAL
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis; Photosensitizing Agents; Dermatologic Agents; Aminolevulinic Acid; Methyl 5-aminolevulinate
• Other Study ID Numbers: 2013-001389-40

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: International peer-reviewed publication