Normal Skin Clinical Trial
Official title:
Thermo-mechanical Fractional Injury Enhances Skin Surface- and Epidermal- Protoporphyrin IX Fluorescence: Comparison of 5-aminolevulinic Acid in Cream and Gel Vehicles
This study investigates a relatively new device TMFI and incubation of ALA in a cream-vehicle and a gel-vehicle.
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.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT02889159 -
Immunologic Profile of Chronically Photodamaged Skin
|
Phase 4 |