Clinical trial NCT02464709: Daylight PDT for Actinic Keratoses: a Multicentre Study Comparing Two Photosensitizers (BF-200 ALA Versus MAL)
Official title: Daylight Mediated Photodynamic Therapy for Actinic Keratoses: a Multicentre Study Comparing Two Photosensitizers (BF-200 ALA Versus MAL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Actinic Keratosis
Natural Daylight Photodynamic Therapy
Keywords: Actinic Keratosis
Photodynamic Therapy
Natural Daylight
Lead sponsor: Joint Authority for Päijät-Häme Social and Health Care
Sponsor class: OTHER
Collaborators: name: Päijänne Tavastia Central Hospital
name: Tampere University Hospital
name: Vaasa Central Hospital, Vaasa, Finland
name: Tampere University
name: STUK - Radiation and Nuclear Safety Authority: Finland
First posted: 2015-06-08
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study compares two photosensitizing creams' BF-200 ALA's (aminolevulinic acid, Ameluz®) and MAL's (methyl 5-aminolevulinate, Metvix®) efficacy on actinic keratoses in natural daylight photodynamic therapy (NDL-PDT). The participants' facial skin or scalp will be randomized in two sides and one side is treated with BF-200 ALA and the other side with MAL. Result of the treatment is assessed with clinical examination 12 months after treatment. The investigators will also compare delayed skin reactions after treatment and cost-effectiveness of both photosensitizer creams.

Detailed description: Photodynamic therapy (PDT) is a widely used method in dermatology clinics for treatment of superficial skin cancers and premalignant lesions. Actinic keratoses (AKs) are premalignant skin lesions which develop due to long-lasting sun exposure and in time can progress into squamocellular skin cancer if left untreated. The incidence of AKs and skin cancers is rapidly booming as the elderly population increases in western countries. It is crucial to treat AKs early and effectively considering their tendency to progress into malign cancer. The current general consensus for treating AKs is to treat large sun-damaged skin areas simultaneously instead of separate AK lesions. Term "skin field cancerization" refers to presence of different degrees of visible and invisible dysplastic changes in widely sun-damaged skin. Natural daylight mediated photodynamic therapy (NDL-PDT) is a well-suited method for treating large field-cancerized skin areas.

In PDT a photosensitizing cream is applied on the skin and let to absorb. After absorption to the skin cells the photosensitizer changes into protoporphyrin IX (PpIX). PpIX reacts with visible light causing a phototoxic reaction which destroys cancer cells targetedly. After absorption the skin can be illuminated using a red lamp (conventional PDT) or natural daylight (NDL-PDT) as the absorption spectrum peaks of PpIX are within the visual spectrum of light.

In Finland the approved photosensitizers for PDT are methyl 5-aminolevulinate cream (MAL, Metvix®, Galderma) and aminolevulinic acid gel (BF-200 ALA, Ameluz®, Biofrontera AG). They both have been clinically studied and proved effective in conventional PDT but in NDL-PDT mainly MAL has been in focus of studies. To our knowledge there is only research report concerning the use of BF-200 ALA in NDL-PDT (Neittaanmaki-Perttu et al 2014) which is a study of our own research group. In this study BF-200 ALA appeared to be more effective than MAL.

Eligibility criteria: Inclusion Criteria:

* Patients with widespread AK lesions symmetrically on face or scalp (at least 3 actinic keratoses symmetrically on face or scalp)
* AKs of grade I-II

Exclusion Criteria:

* Thick grade III AKs
* Previous treatment for actinic keratosis on the same skin area during preceding 6 months
* Porfyria or solar dermatitis
* Allergy for photosensitizers used in the study
* Pregnant or breastfeeding patients
* Impaired general condition (patient can't manage required 2 hours in sunlight outdoors)

Primary outcomes:
measure: Clinical healing of actinic keratoses
timeFrame: 12 months
Secondary outcomes:
measure: Assessing pain experienced by participants: comparing the difference in symmetrical treatment areas of face or scalp
timeFrame: 1 day
Other outcomes:
measure: Primary treatment reaction of skin
timeFrame: 1 week
measure: Dermatoecological analyses of the treatment costs
timeFrame: 12 months
Locations:
city: Lahti
country: Finland
facility: Päijät-Häme Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Vaasa
country: Finland
facility: Vaasa Central Hospital
Study officials:
affiliation: Päijänne Tavastia Central Hospital
name: Janne Rasanen, Lic. Med.
role: PRINCIPAL_INVESTIGATOR
affiliation: Päijänne Tavastia Central Hospital
name: Mari Gronroos, D.Med.Sc.
role: STUDY_DIRECTOR
affiliation: Helsinki University Central Hospital
name: Noora Neittaanmaki-Perttu, D.Med.Sc.
role: STUDY_CHAIR
affiliation: Päijänne Tavastia Central Hospital
name: Mari Salmivuori, Lic. Med.
role: STUDY_CHAIR
affiliation: Tampere University Hospital
name: Leea Ylitalo, D.Med.Sc.
role: STUDY_CHAIR
affiliation: Vaasa Central Hospital, Vaasa, Finland
name: Johanna Hagman, D.Med.Sc.
role: STUDY_CHAIR
affiliation: Vaasa Central Hospital, Vaasa, Finland
name: Ida Knutar, Lic. Med.
role: STUDY_CHAIR
References:
citation: Rasanen JE, Neittaanmaki N, Ylitalo L, Hagman J, Rissanen P, Ylianttila L, Salmivuori M, Snellman E, Gronroos M. 5-aminolaevulinic acid nanoemulsion is more effective than methyl-5-aminolaevulinate in daylight photodynamic therapy for actinic keratosis: a nonsponsored randomized double-blind multicentre trial. Br J Dermatol. 2019 Aug;181(2):265-274. doi: 10.1111/bjd.17311. Epub 2019 Jan 2.