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.

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

Skin Diseases

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.

Group I (Standard DL-PDT)

Group II (DL-PDT with microneedles)

Group III (DL-PDT with CO2 laser)

Group IV (DL-PDT with microdermabrasion)

Transepidermal Application of Metilaminolevulinate in Daylight Photodynamic Therapy in the Treatment of Photodamaged Skin

Numbers of Actinic keratoses on the face: count of lesions before treatment and one
month/three months/six months after the second session.

Actinic keratoses will be classified by degrees of thickness (grades 1, 2 and 3), based
on the Olsen scale (J Am Acad Dermatol. 1991 May;24(5 Pt 1):738-43), before treatment and
one month/three months/six months after the second session.

The overall improvement of photodanificated skin was evaluated using the GAIS scale
(Global Aesthetic Improvement Scale) which ranges from: 1 = very much improvement; 2 =
marked improvement; 3 = improved; 4 = no change; 5 = worse. Also performed before
treatment and one month/three months/six months after the second session.

Clinical Professor

Morphologic study: the aspect of the corneal layer and epidermis, the thickness of the
epidermis (distance between granular layer and basal layer), the extension of the
keratinocytes atypia, the amount and cytological aspect of melanocytes, the thickness of
the subepidermal collagen (distance between membrane basal and onset of solar elastosis
in the papillary dermis), distribution of solar elastosis (diffuse or compact
distribution), the presence and the type of inflammatory infiltrate, the presence or
absence of ectasia in the papillary dermis vessels. These measurements were performed
through an ocular lens with a millimeter ruler (Olympus).

Orcein (morphologic study): the distribution of solar elastosis and the organization of
the elastic fibers (elaunin and oxytalan fibers present in the papillary dermis and
dermo-epidermal junction).

Picrosirius (morphometry of dermis collagen)

Expression of these substrates:

Ki 67, P53 (wild type and mutated): percentage and extent (1/3, 2/3 or 3/3) in the
epidermis

Collagen type I and III, MMP 1,3,9, TIMP 1: semiquantitative method: 0, absence of
expression; +, weak expression; ++, moderate expression; +++, strong expression.

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.

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.

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.

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.

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

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the participation requirements?

Locations

Location

Status