Clinical trial NCT04221126: TMFI Enhances Skin Surface and Epidermal PpIX Fluorescence
Official title: Thermo-mechanical Fractional Injury Enhances Skin Surface- and Epidermal- Protoporphyrin IX Fluorescence: Comparison of 5-aminolevulinic Acid in Cream and Gel Vehicles
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Normal Skin
Keywords: protoporphyrin ix
5-aminolevulinic acid
thermo-mechanical intervention
normal skin
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
First posted: 2020-01-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study investigates a relatively new device TMFI and incubation of ALA in a cream-vehicle and a gel-vehicle.

Detailed description: Topical photodynamic therapy (PDT) is a well-established treatment for dermatological pre-malignant actinic keratoses and Morbus Bowen as well as selected cases of basal cell carcinomas. PDT is exceedingly well suited for treatment of larger skin areas and provide excellent cosmetic results. PDT is based on the photosensitizing drug 5-aminolevulinic acid (5-ALA) that is metabolized into the light-sensitive Protoporphyrin IX, and activated in the skin by light in the visible spectrum. When skin incubated with 5-ALA subsequently is exposed to light, photoactivated PpIX catalyzes a photochemical reaction, which leads to cell apoptosis of the dysplastic or neoplastic tissue. The amount of PpIX fluorescence in the skin is estimated by PpIX fluorescence measurements on skin surface by fluorescence photographs and in the skin depth with fluorescence microscopy. Previous studies have suggested an association of the amount of PpIX in the skin and the clinical outcome of PDT.

The highly lipophilic nature of the stratum corneum (SC) provides the main barrier for influx of drugs and environmental chemicals into the body (6). SC is the greatest impediment for uptake of 5-ALA and the formation of PpIX can be increased by modifying the SC. Pretreatment of the skin facilitates local uptake of photosensitizing agents and is therefore recommended to obtain optimal outcomes in PDT. Recently, different energy-based devices have been introduced for PDT pretreatment to disrupt the SC barrier and effectively increase PpIX accumulation. However, current light-based treatments, such as ablative and non-ablative lasers, are painful to patients and induce thermal damage that result in oozing, crusting or peeling of the skin.

To increase cutaneous absorption with minimal damage to the skin, thermo-mechanical fractional intervention (TMFI) has been introduced as a new technology. TMFI rapidly transfer thermal energy by a metallic pyramid tip that enable skin contact through integrated pulsed movements. The rapid heating dehydrates the epidermis and superficial dermis and create micropores with no coagulative damage of surrounding tissue. The amount of thermal energy delivered can be adjusted by pulse duration and by the protrusion depth of the tip that sets the thermal matching between the tip and the skin. TMFI has in one study shown to increase uptake of hydrophilic drugs compared with no skin pretreatment. As TMI dehydrates the epidermis, hydrophilic drugs dissolved in a low viscosity liquid-based vehicle may be more readily distributed within the skin compared to drugs dissolved in a high viscosity vehicle.

The investigators hypothesize that i) TMFI increases 5-ALA induced PpIX accumulation compared with no pretreatment and that ii) TMFI + 5-ALA in a low viscosity vehicle formulation enhances PpIX skin biodistribution compared with 5-ALA in a high viscosity vehicle formulation.

Potentially, TMFI pretreatment could improve PpIX biodistribution and reduce photosensitizer incubation time to obtain sufficient PpIX accumulation. This could significantly benefit thousands of patients who each year undergo PDT for dysplastic skin lesions.

Eligibility criteria: Inclusion Criteria: Healthy participants above 18 years of age

* Fitzpatrick skin type I-III and normal skin on the upper back
* Fertile women with negative U-hCG and use of safe anticontraceptive during the entire study period e.g. oral hormonal contraceptives, intrauterine devices, subdermal implantation or hormonal vaginal ring
* Provided informed written consent

Exclusion Criteria:

* No previous PDT or laser treatment within the past 6 months in the study areas
* Pregnant or lactating women
* Participants with known allergy to 5-ALA, lidocaine or any excipients to components in the vehicles
* Considered unable to follow the study protocol

Primary outcomes:
measure: Change in PpIX fluorescence at skin surface following TMFI and topical 5-ALA in gel and cream vehicle
timeFrame: Baseline and in 30-minute intervals until 3 hours
measure: PpIX fluorescence biodistribution inside skin
timeFrame: 3 hours
Secondary outcomes:
measure: Histological skin interactions after TMFI
timeFrame: 3 hours
measure: Severity of local skin reactions
timeFrame: 5 minutes after TMFI pretreatment
measure: Severity of local skin reactions
timeFrame: 3 hours after TMFI pretreatment
measure: Severity of local skin reactions
timeFrame: 14 days after TMFI pretreatment
measure: Presence of perceived pain during treatment
timeFrame: During the actual TMFI pretreatment, estimated 1-2 minute per participant
measure: Safety including wounding, scarring, hyper and hypo pigmentation
timeFrame: 14 days
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
state: Copenhagen NV
Study officials:
affiliation: Bispebjerg Hospital
name: Merete Hædersdal, DMSc
role: STUDY_DIRECTOR
References: