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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03006185

Enrollment

Registered

2016-12-30

Start date

2016-08-31

Completion date

2017-03-01

Last updated

2022-09-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Brief summary

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

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.

Interventions

DEVICEAblative Fractional Carbon Dioxide (CO2) Laser

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.

DEVICEMicrodermabrasion

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.

Study design

Allocation

RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

DOUBLE (Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Complete Clearance (%) of Actinic Keratoses (AKs)	12-15 weeks post-treatment	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.

Secondary

Measure	Time frame	Description
Severity of Local Skin Reactions (LSRs)	Day 3-6 post treatment	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.
Degree of Sun Damage	12-15 weeks post-treatment	Sun damage is evaluated clinically on a 4 point scale where 0 = none, 1= mild, 2= moderate and 3= severe sun damage.
Treatment-related Pain	during treatment (day 0)	Patient-reported pain during treatments is evaluated using the visual analog scale (VAS) where 0= no pain and 10= worst imaginable pain.
New Actinic Keratoses (AKs)	12-15 weeks post-treatment	Number of new actinic keratoses (AKs) identified clinically 12-15 weeks after treatment and that were not present at the baseline evaluation.
Investigator-reported Cosmesis (Clinical Evaluation)	12-15 weeks post-treatment	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.
Patient-reported Cosmesis	12-15 weeks post-treatment	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
Patient Pretreatment Preference	12-15 weeks post-treatment	Patients were asked to report which pretreatment they preferred: Laser, microdermabrasion, or no preference
Treatment-related Side Effects	up to 12-15 weeks post-treatment	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.

Participant flow

Participants by arm

Arm	Count
Split Person Design: Pretreatment With Ablative Fractional Carbon Dioxide Laser or Microdermabrasion Two 50 cm2 test areas (Test Area A and B) are demarcated on the skin of each study participant. One test area is randomized to receive the intervention: Ablative Fractional Carbon Dioxide (CO2) Laser prior to standard daylight photodynamic therapy. The other test area is randomized to receive the intervention: microdermabrasion prior to standard daylight photodynamic therapy. Ablative Fractional Carbon Dioxide (CO2) Laser: Ablative Fractional Carbon Dioxide (CO2) Laser treatment is randomly allocated to one of two tests areas in each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy. Microdermabrasion: Microdermabrasion (processing of the skin with a sandpaper-like material) is randomly allocated to one of two tests areas in each study participant. Microdermabrasion treatment consists of targeted treatment of actinic keratoses and field treatment of the entire test area. Afterwards, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area then undergoes 2 hours of daylight photodynamic therapy.	18
Split Person Design: Pretreatment With Ablative Fractional Carbon Dioxide Laser or Microdermabrasion Two 50 cm2 test areas (Test Area A and B) are demarcated on the skin of each study participant. One test area is randomized to receive the intervention: Ablative Fractional Carbon Dioxide (CO2) Laser prior to standard daylight photodynamic therapy. The other test area is randomized to receive the intervention: microdermabrasion prior to standard daylight photodynamic therapy. Ablative Fractional Carbon Dioxide (CO2) Laser: Ablative Fractional Carbon Dioxide (CO2) Laser treatment is randomly allocated to one of two tests areas in each study participant. Laser treatment consists of targeted ablation of actinic keratoses and field laser treatment of the entire test area. After laser treatment, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area thereafter undergoes 2 hours of daylight photodynamic therapy. Microdermabrasion: Microdermabrasion (processing of the skin with a sandpaper-like material) is randomly allocated to one of two tests areas in each study participant. Microdermabrasion treatment consists of targeted treatment of actinic keratoses and field treatment of the entire test area. Afterwards, application of methyl aminolevulinate (MAL), a topical photosensitising agent, is performed. The test area then undergoes 2 hours of daylight photodynamic therapy.	36
Total	54

Baseline characteristics

Characteristic	Split Person Design: Pretreatment With Ablative Fractional Carbon Dioxide Laser or Microdermabrasion
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	15 Participants
Age, Categorical Between 18 and 65 years	3 Participants
Age, Continuous	72.5 years
Region of Enrollment Denmark	18 participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	12 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 18
other Total, other adverse events	3 / 18
serious Total, serious adverse events	0 / 18

Outcome results

Primary

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.