Actinic Keratoses
Conditions
Keywords
Actinic keratoses, Daylight-PDT, Hexylaminolaevulinate, HAL, Methylaminolaevulinate, MAL, Hyperspectral imaging
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.
Interventions
DRUGHexylaminolaevulinate cream
0.2% Hexylaminolaevulinate (Hexvix, Photocure) mixed with Unguentum M (Allmiral) cream (2014)
DRUGMethylaminolaevulinate cream
MAL 16% is used as photosensitizer for daylight-PDT
Sponsors
Helsinki University Central Hospital
Joint Authority for Päijät-Häme Social and Health Care
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
-Symmetrical actinic damage on face or scalp
Exclusion criteria
* Pregnancy * Lactation * Allergy to photosensitizer * Photodermatose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Histological Lesion Clearance | Baseline, 3 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Lesion Clearance | Baseline, 3 months | Clinical lesion clearance is observed by a blinded observer |
| Adverse Reactions | One week | 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. |
| Pain Assesment (Visual Analog Scale) | 12 hours | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Clearance of Field Cancerization in Hyperspectral Images | 3 months | Data not collected |
Countries
Finland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hexylaminolaevulinate and Methylaminoalevulinate Cream 0.2% hexylaminolaevulinate (Hexvix, Photocure) mixed with Unguentum M (Allmiral) and 16% methylaminolaevulinate (Metvix, Galderma) in a split-face design | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Hexylaminolaevulinate and Methylaminoalevulinate Cream |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 79 years |
| Region of Enrollment Finland | 14 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 14 | 14 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 |
Outcome results
Primary
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)
Time frame: Baseline, 3 months
Population: One patient was excluded from the histological analysis because one biopsied lesion clinically taken as an AK appeared histologically to be seborrheic eczema.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hexylaminolaevulinate Cream | Histological Lesion Clearance | 38.5 percentage of complete histological clea |
| Methylaminolaevulinate Cream | Histological Lesion Clearance | 69.2 percentage of complete histological clea |
Secondary
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.
Time frame: One week
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hexylaminolaevulinate Cream | Adverse Reactions | 14 participants |
| Methylaminolaevulinate Cream | Adverse Reactions | 14 participants |
Secondary
Clinical Lesion Clearance
Clinical lesion clearance is observed by a blinded observer
Time frame: Baseline, 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hexylaminolaevulinate Cream | Clinical Lesion Clearance | 73.4 percentage of lesions in complete respon |
| Methylaminolaevulinate Cream | Clinical Lesion Clearance | 77.8 percentage of lesions in complete respon |
Secondary
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.
Time frame: 12 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hexylaminolaevulinate Cream | Pain Assesment (Visual Analog Scale) | 0.86 Mean maximal pain VAS score |
| Methylaminolaevulinate Cream | Pain Assesment (Visual Analog Scale) | 1 Mean maximal pain VAS score |
Other Pre-specified
Clearance of Field Cancerization in Hyperspectral Images
Data not collected
Time frame: 3 months