Transepidermal Application of Metilaminolevulinate in Daylight PDT in the Treatment of Photodamaged Skin

NCT ID: NCT03963765

Last Updated: 2021-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-03
• Study Completion Date: 2020-12-01

Brief Summary

Chronic sun exposure enhances the incidence of cutaneous neoplasms (NMSC - non melanoma skin cancer), wrinkles, roughness, telangiectasia and irregular pigmentation of the skin. Nowadays, actinic keratosis (AK) are considered in situ squamous cell carcinoma (SCC), and should be managed that way. Conventional topical Photodynamic therapy (PDT) has proven its efficacy on treatment of AK and cancerization field. PDT's action in global improvement of photodamaged skin, texture, pigmentation and reduction of wrinkles has been well documented in literature. Immunohistochemical and histopathological essays describe the hypothesis of conventional PDT's mechanisms of action in photoaging by dermal remodeling, with enhancement of collagen, statiscally significant. Daylight-Photodynamic Therapy (DL-PDT) is a new modality that keeps the efficacy of topical PDT in treatment of AK and cancerization field, but painless and more practically. Until this moment, there is no report of DL-PDT efficacy on photorejuvenation and actinic keratosis evaluated by clinical, histopathological and immunohistochemical studies. The investigator's aim is to evaluate the alterations induced by isolated DLPDT or DLPDT associated with other techniques of transepidermal drug delivery (microneedles, CO2 laser and microdermabrasion) in the treatment of field cancerization in photodamaged skin with actinic keratosis, through clinical evaluation, histopathological and immunohistochemical studies. It is an interventional, prospective, randomized controlled, parallels-groups, four-arm trial with 1:1 allocation ratio study performed in forty patients attended at the Dermatology Service of Hospital Universitário Antonio Pedro- Universidade Federal Fluminense.

Detailed Description

This is a randomized controlled, parallels-groups, four-arm trial with 1:1 allocation ratio study on the clinical, histological and immunohistochemical changes induced by Daylight-Photodynamic Therapy (DL-PDT) in 40 patients presenting face-photodamaged skin with actinic keratosis, attended at the Dermatology outpatient clinic of Hospital Antônio Pedro (HUAP) of Universidade Federal Fluminense - UFF, who meet the inclusion criteria and agree to sign the informed consent form (TCLE) for participation in clinical research. There will be four treatment groups with different protocols. These protocols were chosen by hand draw using two boxes containing folded papers. One with the 4 numbers of the groups (1, 2, 3, 4), and another with 4 papers with the names of the protocols. At each draw, one paper from each box was withdrawn, and the combined results from the two boxes defined the treatments of each group. Group I was randomly selected to be DL-PDT alone (standard procedure - group control); Group II was randomly selected to be DL-PDT with TED (microneedles); Group III was randomly selected to be DL-PDT with TED (CO2 laser) and Group IV was was randomly selected to be DL-PDT with TED (microdermabrasion with crystal peeling). Two treatment sessions will be performed with a 4-week interval, regardless of the protocol chosen per group. Patients will be numbered according to the registration for participation in the study. These numbers will be distributed in 4 groups randomly through the computer, using an Apple application called Random (random number generator: seller Mireia Lluch Ortoloa, category utilities, version 1). Each DL-PDT session will consist of: superficial skin curettage all face with a dermatological curette; application of pure chemical sunscreen for 15 minutes; application of methyl-aminolevulinate (Metvix®, GALDERMA), approved by ANVISA under Registration No. 1291600650016, for 30 minutes without occlusion, before exposure to daylight for 2 hours. Regarding the association of techniques, these will be varied according to the group. For clinical evaluation, patient data will be recorded on the evaluation form, and photographs with the same position and lighting patterns will be performed before and after predetermined periods. For histological and immunohistochemical evaluations, skin biopsies will be performed before and after 3 months of the last treatment session.

Conditions

Skin Diseases

Study Design

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

Study Groups

Group I (Standard DL-PDT)

1. Superficial skin curettage all face with a dermatological curette

2. All exposed skin was covered with pure chemical sunscreen

3. After 15 minutes, a uniform layer of methyl-aminolevulinate (MAL) (Metvix®, Galderma- 1g) was applied to the face without occlusion

In all protocols, the patients remained indoor for 30 min after procedures and then exposed to daylight in an open environment for 2 hours. After this period, the skin was cleaned with 0.9% saline, and the sunscreen reapplied.

Group Type: ACTIVE_COMPARATOR

Group I (Standard DL-PDT)

Intervention Type: PROCEDURE

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®)

Group II (DL-PDT with microneedles)

1. Superficial skin curettage all face with a dermatological curette

2. All exposed skin was covered with pure chemical sunscreen

3. After 15 minutes, a uniform layer of methyl-aminolevulinate (MAL) (Metvix®, Galderma- 1g) was applied to the face without occlusion

4. A motorized pen with a tip of 17 grouped needles with 0,5mm (Dermapen Beauty®- Korea) was applied without bleeding

In all protocols, the patients remained indoor for 30 min after procedures and then exposed to daylight in an open environment for 2 hours. After this period, the skin was cleaned with 0.9% saline, and the sunscreen reapplied.

Group Type: EXPERIMENTAL

Group II (DL-PDT with microneedles)

Intervention Type: PROCEDURE

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®) and Microneedles - motorized pen with a tip of 17 grouped needles with 0,5mm (Dermapen Beauty®- Korea) as a techniques of transepidermal drug delivery (TED)

Group III (DL-PDT with CO2 laser)

1. Superficial skin curettage all face with a dermatological curette

2. All exposed skin was covered with pure chemical sunscreen

3. After 15 minutes and removing excess sunscreen, Ablative Fractional Laser (AFXL), CO2 laser, roller-type ferrule, composed of one row with seven fractionating pins (7x1), 60 W, 15 mJ/pixel, 125μm/pixel, 2 mm spacing between ablation zones, density <1% (Pixel Alma Lasers ®) was applied, single-pass

4. A uniform layer of methyl-aminolevulinate (MAL) (Metvix®, Galderma- 1g) was applied to the face without occlusion

In all protocols, the patients remained indoor for 30 min after procedures and then exposed to daylight in an open environment for 2 hours. After this period, the skin was cleaned with 0.9% saline, and the sunscreen reapplied.

Group Type: EXPERIMENTAL

Group III (DL-PDT with CO2 laser)

Intervention Type: PROCEDURE

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®) and Ablative Fractional Laser (AFXL), CO2 laser, roller-type ferrule, composed of one row with seven fractionating pins (7x1), 60 W, 15 mJ/pixel, 125μm/pixel, 2 mm spacing between ablation zones, density \<1% (Pixel Alma Lasers ®) was applied, single-pass

Group IV (DL-PDT with microdermabrasion)

1. Superficial skin curettage all face with a dermatological curette

2. Microdermabrasion with aluminum oxide crystal (Pan Eletronic®) was performed after superficial skin curettage. Three passes on the skin in different directions (vertical, horizontal, and oblique) were applied

3. All exposed skin was covered with pure chemical sunscreen

4. After 15 minutes, a uniform layer of methyl-aminolevulinate (MAL) (Metvix®, Galderma- 1g) was applied to the face without occlusion

In all protocols, the patients remained indoor for 30 min after procedures and then exposed to daylight in an open environment for 2 hours. After this period, the skin was cleaned with 0.9% saline, and the sunscreen reapplied.

Group Type: EXPERIMENTAL

Group IV (DL-PDT with microdermabrasion)

Intervention Type: PROCEDURE

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®) and Microdermabrasion - aluminum oxide crystal (Pan Eletronic®) as a techniques of transepidermal drug delivery (TED)

Interventions

Group I (Standard DL-PDT)

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®)

Intervention Type: PROCEDURE

Group II (DL-PDT with microneedles)

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®) and Microneedles - motorized pen with a tip of 17 grouped needles with 0,5mm (Dermapen Beauty®- Korea) as a techniques of transepidermal drug delivery (TED)

Intervention Type: PROCEDURE

Group III (DL-PDT with CO2 laser)

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®) and Ablative Fractional Laser (AFXL), CO2 laser, roller-type ferrule, composed of one row with seven fractionating pins (7x1), 60 W, 15 mJ/pixel, 125μm/pixel, 2 mm spacing between ablation zones, density \<1% (Pixel Alma Lasers ®) was applied, single-pass

Intervention Type: PROCEDURE

Group IV (DL-PDT with microdermabrasion)

Daylight photodynamic therapy with photosensitizer (MAL - Metvix, Galderma ®) and Microdermabrasion - aluminum oxide crystal (Pan Eletronic®) as a techniques of transepidermal drug delivery (TED)

Intervention Type: PROCEDURE

Other Intervention Names

Daylight PDT; Daylight PDT with microneedles; Daylight PDT with CO2 laser; Daylight PDT with microdermabrasion

Eligibility Criteria

Inclusion Criteria

• Both gender;
• Fitzpatrick phototypes I - IV;
• age between 40 and 75 years;
• photodamaged skin with at least 1 lesion of actinic keratosis

Exclusion Criteria

• Pregnancy and lactation;
• photosensitivity;
• smoking;
• malignant neoplasms;
• infections;
• immunosuppression;
• collagenoses;
• any systemic disease or emotional/psychological disorder that could contraindicate the procedure.
• any topical treatment or interventions for at least three months before the study started

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universidade Federal Fluminense

OTHER

Sponsor Role: lead

Responsible Party

Maria Claudia Almeida Issa

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria Claudia Issa

Role: PRINCIPAL_INVESTIGATOR

Professor

Locations

Hospital Universitário Antonio Pedro - Universidade Federal Fluminense

Niterói, Rio de Janeiro, Brazil

Countries

Brazil

Other Identifiers

Daylight PDT

Identifier Type: -

Identifier Source: org_study_id