TMFI Enhances Skin Surface and Epidermal PpIX Fluorescence

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04221126
• Other study ID #: 2018-004397-96
• Status: Completed
• Phase: Phase 4
• Start date: April 29, 2019
• Est. completion date: December 9, 2019

Study information

• Verified date: January 2020
• Source: Bispebjerg Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 9, 2019
• Est. primary completion date: August 8, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Normal Skin

Intervention

Device:
• TMFI
Tixel rapidly transfer thermal energy by a metallic pyramid tip that enable skin contact through integrated pulsed movements. The rapid heating dehydrates he epidermis and superficial dermis and creates micropores with no coagulative damage of surronding tissue.

Drug:
• ALA cream
ALA compounded in a cream
• ALA gel
ALA compounded in a gel

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen	Copenhagen NV

Sponsors (1)

Lead Sponsor	Collaborator
Merete Haedersdal

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in PpIX fluorescence at skin surface following TMFI and topical 5-ALA in gel and cream vehicle	Levels of PpIX uptake at the skin surface quantitatively from PpIX imaging.	Baseline and in 30-minute intervals until 3 hours
Primary	PpIX fluorescence biodistribution inside skin	Levels of PpIX uptake inside predefined skin regions: Epidermis, superficial dermis, mid dermis and deep dermis evaluated on fluorescence microscopy images. Biopsies used for fluorescence microscopy was sampled after 3 hours.	3 hours
Secondary	Histological skin interactions after TMFI	Biopsies were stained with haematoxylin and eosin (HE) for light microscopy for histopathology analysis of TMFI effect on the skin. Depth and width of the TMFI effect on the skin was measured.	3 hours
Secondary	Severity of local skin reactions	Local skin reaction (LSR)-grading scale. Evaluation of redness, scaling, edema, pustules, and erosion on a 5-point categorial scale of severity. Scores are 0, 1, 2, 3, and 4, for individual parameters: Redness: None, slightly pink <50%, pink or light red >50%, red restricted to treatment area, and red extending outside treatment area.; Scaling: None, isolated scale, scaling <50%, scaling >50%, scaling extending outside treatment area.; Edema: None, slight specific edema, palpable edema beyond individual lesions, confluent and/or visible edema, and marked swelling extending outside treatment area.; Pustules: None, vesicles only, transudate or pustules <50%, transudate or pustules >50%, and transudate or pustules extending outside treatment area.; Erosion: None, lesion specific erosion, erosion extending beyond individual lesion, erosion >50%, and black eschar or ulceration.	5 minutes after TMFI pretreatment
Secondary	Severity of local skin reactions	Local skin reaction (LSR)-grading scale. Evaluation of redness, scaling, edema, pustules, and erosion on a 5-point categorial scale of severity. Scores are 0, 1, 2, 3, and 4, for individual parameters: Redness: None, slightly pink <50%, pink or light red >50%, red restricted to treatment area, and red extending outside treatment area.; Scaling: None, isolated scale, scaling <50%, scaling >50%, scaling extending outside treatment area.; Edema: None, slight specific edema, palpable edema beyond individual lesions, confluent and/or visible edema, and marked swelling extending outside treatment area.; Pustules: None, vesicles only, transudate or pustules <50%, transudate or pustules >50%, and transudate or pustules extending outside treatment area.; Erosion: None, lesion specific erosion, erosion extending beyond individual lesion, erosion >50%, and black eschar or ulceration.	3 hours after TMFI pretreatment
Secondary	Severity of local skin reactions	Local skin reaction (LSR)-grading scale. Evaluation of redness, scaling, edema, pustules, and erosion on a 5-point categorial scale of severity. Scores are 0, 1, 2, 3, and 4, for individual parameters: Redness: None, slightly pink <50%, pink or light red >50%, red restricted to treatment area, and red extending outside treatment area.; Scaling: None, isolated scale, scaling <50%, scaling >50%, scaling extending outside treatment area.; Edema: None, slight specific edema, palpable edema beyond individual lesions, confluent and/or visible edema, and marked swelling extending outside treatment area.; Pustules: None, vesicles only, transudate or pustules <50%, transudate or pustules >50%, and transudate or pustules extending outside treatment area.; Erosion: None, lesion specific erosion, erosion extending beyond individual lesion, erosion >50%, and black eschar or ulceration.	14 days after TMFI pretreatment
Secondary	Presence of perceived pain during treatment	VAS Visual analogue scale for perceived pain. Scores are 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, ranging from none to very severe. Higher is worse, and lower scores for treatment modalities are desirable.	During the actual TMFI pretreatment, estimated 1-2 minute per participant
Secondary	Safety including wounding, scarring, hyper and hypo pigmentation	Safety concerning side-effects evaluated on a 5-point categorial scale for hyper- and hypopigmentation, erosions, and scarring. Scores are 0, 1, 2, 3, and 4, for none, mild, moderate, severe, and very severe. A lower score is desirable.	14 days