Laser and Microdermabrasion Before Photodynamic Therapy for Actinic Keratoses in Field-cancerized Skin

Study Overview
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Brief Summary
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Comparison of treatment efficacy and safety of pretreatment with ablative fractional laser versus microdermabrasion combined with large-area photodynamic therapy with methyl aminolevulinate for actinic keratoses

Detailed Description
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For each study participant, two test areas (A and B) are demarcated in the same anatomical region, with each area containing no less than 5 actinic keratoses (AKs). Test areas are randomized to receive skin pretreatment of EITHER ablative fractional laser OR microdermabrasion prior to photodynamic therapy using methyl aminolevulinate. Efficacy, local skin reactions and safety of both test areas are evaluated over a 12-15 week follow up period.

Official Title
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Pretreatment With Ablative Fractional Laser and Microdermabrasion Before Photodynamic Therapy for Actinic Keratoses in Field-cancerized Skin

Conditions
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Actinic Keratosis, Sun Damaged Skin, Solar Keratosis, Solar Skin Damage

Intervention / Treatment
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* Device: Ablative Fractional Carbon Dioxide (CO2) Laser
* Device: Microdermabrasion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with two skin areas of at least 50 cm2 with a minimum of 5 actinic keratoses (AKs) grade I-III, chronically sun damaged field changes in one of the following anatomical regions: face, scalp, upper chest. Patients who have given written informed consent and are believed to be capable of following the study protocol. Fertile women must have a negative pregnancy test (urine-hCG) at the time of inclusion and use anti-contraception (oral contraceptives, intrauterine device, gestagen depot injection, subdermal implantation, vaginal ring, transdermal depot bandage or sterilisation) during the study. Exclusion Criteria: Patients that have within the last month received local treatment in the test areas. Pregnant or nursing patients. Patients with porphyria Patients with skin cancer, keratoacanthoma, or other infiltrating tumors within the test areas. Patients with a tendency to develop hypertrophic scars or keloids. Patients with a known allergy to Metvix cream Patients that are believe unlikely to follow the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Split-Person Design: Ablative Fractional Carbon Dioxide (CO2) Laser vs Microdermabrasion<br>WIthin each participant, two 50 cm2 adjacent test areas were randomized to laser or microdermabrasion pretreatment prior to daylight photodynamic therapy. | Device: Ablative Fractional Carbon Dioxide (CO2) Laser<br>* One 50 cm2 test area was randomized to pretreatment using a fractional 2940 nm Er:YAG laser (Joule®; Sciton Inc., Palo Alto, CA, USA). To remove hyperkeratosis, a fully-ablative 4 mm handpiece was optionally applied, followed by a single pass of a fractional Profrax 430 handpiece for all AKs. Subsequent field treatment consisted of a single pass of the Profrax 430 handpiece over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.<br>Device: Microdermabrasion<br>* Another adjacent 50 cm2 test area was exposed to microdermabrasion using an MD pad with 58.5 µm-diameter particles (Ambu® Skin Prep Pads 2121M; Ambu A/S, Ballerup, Denmark). Lesion-directed treatment consisted of an increasing number of swipes concentrated to AK lesions. During field treatment, multiple swipes were applied in perpendicular directions over the entire test area. Immediately after pretreatment, a 0.5 mm layer of methyl aminolevulinate (Metvix ® cream 16%; Galderma, Paris, France) was applied. After 30 minutes, patients were exposed to 2 hours of ambient daylight, according to approved procedure. After light exposure, cream was wiped off and test areas were covered for the remainder of the day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Clearance (%) of Actinic Keratoses (AKs) | Percentage clearance of baseline actinic keratoses (AKs), determined by the ratio of AK lesions that are clinically resolved 12-15 weeks after treatment compared to the AK number at baseline. | 12-15 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New Actinic Keratoses (AKs) | Number of new actinic keratoses (AKs) identified clinically 12-15 weeks after treatment and that were not present at the baseline evaluation. | 12-15 weeks post-treatment | 
| Severity of Local Skin Reactions (LSRs) | Local skin reactions scale (min:0; better and max: 3; worse) used to grade each of the following parameters: erythema, edema, crusting, pustules, ulceration and scabbing, scaling. The severity of each evaluated clinically on a 4-point scale where 0 = none, 1= mild, 2= moderate and 3= severe. With 7 parameters the sum of all scores will produce a maximum composite score of 21. | Day 3-6 post treatment | 
| Degree of Sun Damage | Sun damage is evaluated clinically on a 4 point scale where 0 = none, 1= mild, 2= moderate and 3= severe sun damage. | 12-15 weeks post-treatment | 
| Treatment-related Pain | Patient-reported pain during treatments is evaluated using the visual analog scale (VAS) where 0= no pain and 10= worst imaginable pain. | during treatment (day 0) | 
| Treatment-related Side Effects | Side effects are evaluated over the course 12-15 weeks following treatment. In addition to unforeseen adverse events, specific side effects including the clinical presence of infection, scarring, hypopigmentation and hyperpigmentation are recorded. | up to 12-15 weeks post-treatment | 
| Investigator-reported Cosmesis (Clinical Evaluation) | Cosmetic appearance of treated areas is evaluated by investigators clinically (scores on a scale) using a 4-point scale where 0 = none, 1= acceptable, 2= good and 3= excellent outcome. | 12-15 weeks post-treatment | 
| Patient-reported Cosmesis | Cosmetic appearance is evaluated by patients at the end of the study (scores on a scale) using a 4 point scale where 0 = none, 1= acceptable, 2= good and 3= excellent | 12-15 weeks post-treatment | 
| Patient Pretreatment Preference | Patients were asked to report which pretreatment they preferred: Laser, microdermabrasion, or no preference | 12-15 weeks post-treatment |