Clinical trial NCT03963765: Transepidermal Application of Metilaminolevulinate in Daylight PDT in the Treatment of Photodamaged Skin
Official title: Transepidermal Application of Metilaminolevulinate in Daylight Photodynamic Therapy in the Treatment of Photodamaged Skin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Skin Diseases
Lead sponsor: Universidade Federal Fluminense
Sponsor class: OTHER
First posted: 2019-05-28
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Transepidermic Application of Metilaminolevulinate in Daylight Photodynamic Therapy in the Treatment of Photodamaged Skin
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Quantitative clinical evaluation of Actinic keratoses
timeFrame: 6 months
measure: Qualitative clinical evaluation of Actinic keratoses
timeFrame: 6 months
measure: Qualitative evaluation of global clinical skin change
timeFrame: 6 months
Secondary outcomes:
measure: Histological evaluation: Routine stain - haematoxylin and eosin
timeFrame: 1 year
measure: Histological evaluation: Special stains (Orcein and Picrosirius)
timeFrame: 1 year
measure: Immunohistochemistry: epidermis and dermis
timeFrame: 1 year
Other outcomes:
Locations:
city: Niteroi
country: Brazil
facility: Hospital Universitário Antonio Pedro - Universidade Federal Fluminense
state: Rio De Janeiro
Study officials:
affiliation: Professor
name: Maria Claudia Issa
role: PRINCIPAL_INVESTIGATOR
References: