TMFI Enhances Skin Surface and Epidermal PpIX Fluorescence

NCT ID: NCT04221126

Last Updated: 2020-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-29
• Study Completion Date: 2019-12-09

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.

Conditions

Normal Skin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TMFI +cream

TMFI + ALA cream

Group Type: EXPERIMENTAL

TMFI

Intervention Type: DEVICE

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.

ALA cream

Intervention Type: DRUG

ALA compounded in a cream

TMFI + gel

TMFI + ALA gel

Group Type: EXPERIMENTAL

TMFI

Intervention Type: DEVICE

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.

ALA gel

Intervention Type: DRUG

ALA compounded in a gel

ALA creAM

ALA cream

Group Type: ACTIVE_COMPARATOR

ALA cream

Intervention Type: DRUG

ALA compounded in a cream

ALA GEL

ALA gel

Group Type: ACTIVE_COMPARATOR

ALA gel

Intervention Type: DRUG

ALA compounded in a gel

Control

Untreated control with no intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DEVICE

ALA cream

ALA compounded in a cream

Intervention Type: DRUG

ALA gel

ALA compounded in a gel

Intervention Type: DRUG

Other Intervention Names

Thermo-mechanical fractional injury; 5-aminolevulinic acid compounded in a cream; 5-aminolevulinic acid compounded in a gel

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merete Haedersdal

OTHER

Sponsor Role: lead

Responsible Party

Merete Haedersdal

PhD, Dr. med, Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Merete Hædersdal, DMSc

Role: STUDY_DIRECTOR

Bispebjerg Hospital

Locations

Bispebjerg Hospital

Copenhagen, Copenhagen NV, Denmark

Countries

Denmark

Other Identifiers

2018-004397-96

Identifier Type: -

Identifier Source: org_study_id