Comparison Between 5-aminolevulinic Acid Photodynamic Therapy Versus Cryotherapy for Actinic Keratosis Treatment

Study Overview
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Brief Summary
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This study aims to compare in a prospective and randomized way actinic keratosis treatment with 5-aminolevulinic acid photodynamic therapy versus cryotherapy, from the standpoint of therapeutic efficacy, pain, and cosmetic results.

Detailed Description
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Actinic keratosis is a skin lesion induced by chronic sun exposure with a significant prevalence and malignant potential for squamous cell carcinoma, which makes essential its treatment. Today there are several possible therapies, where cryotherapy is usually applied in our practice. Photodynamic therapy (PDT)is another method also widespread for keratosis which involves the administration of a topical precursor drug which produces endogenous photosensitising substances activated by specific light, selectively destroying the diseased tissue. This study aims to evaluate the use the drug formulation for photodynamic therapy 5-aminolevulinic acid (5-ALA) associated with dimethyl sulfoxide, comparing its efficacy with conventional cryotherapy, and also pain and cosmetic results. This project enrolled 137 outpatients from the Department of Cutaneous Oncology of Barretos Cancer Hospital - Pio XII Foundation, with symmetrical and comparable keratosis in their upper limbs. With the same patient as controls, side arm and therapy to be used were randomized: cryotherapy or photodynamic therapy. For cryotherapy was utilized bottles of liquid nitrogen (Cry-ac, 500ml); and for photodynamic therapy was utilized incoherent red light lamp with a total dosis of 37J/cm² . There was one or two sessions of each therapy , at 0 and 3 months; and three assessments for evaluation were done at 0, 3 and 6 months of onset. The evaluations on efficacy were in terms of area regression, and classified as complete response or no response. Pain was assessed by visual analogue scale, and numerical scale. Cosmesis was evaluated with the presence or not, objectively, of hyper, hypopigmentation or scar retraction. Finally, patient's preference regarding utilized therapeutics was noted by the researcher.

Official Title
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Evaluation of the Formulation of 5-aminolevulinic Acid With Dimethylsulfoxide in Photodynamic Therapy for Treatment of Actinic Keratosis

Conditions
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Actinic Keratosis

Intervention / Treatment
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* Drug: 5-ALA Photodynamic Therapy
* Drug: Cryotherapy with liquid nitrogen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years. Patients with actinic keratoses symmetrical, ie, comparable in the upper limbs ( with the same grade, I, II or III). Patients in accordance with informed consent. Exclusion Criteria: Patients with concomitant skin diseases, congenital or acquired (albinism, vitiligo, xeroderma, Gorlin, etc.) Immunosuppression (HIV, transplanted patients, etc.) Pregnancy or lactation Patients who do not agree with the informed consent initially or during the protocol. Presence of pigmented lesions near the keratoses. Patients with porphyria. Patients who have undergone less than 2 months with some kind of treatment for keratosis in the upper limbs.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-ALA Photodynamic Therapy<br>Topical application of a 2mm of thickness layer of 20% 5-aminolevulinic acid (5-ALA) associated with 20% dimethyl sulfoxide (DMSO) and 3% ethylene diamine acid (EDTA) emulsion, over the actinic keratosis lesion and over a 0,5 cm margin around it. After a 4 hours interval under light protection with plastic film and aluminum foil, the light protection and the emulsion is removed. Then the lesion is lightened with a red (630 nm) incoherent LED lamp AKTILITE CL 128 (PhotoCure ASA, Oslo, Norway) with a total light dose of 37J/cm2.After that dressings are done and kept for 24H, and removed at patient home. | Drug: 5-ALA Photodynamic Therapy<br> <br> * Other names: AKTILITE CL 128 (PhotoCure ASA, Oslo, Norway);|
| Active Comparator: Cryotherapy with liquid nitrogen<br>Topical application of liquid nitrogen spray (500ml Cry-ac ® bottle) over the actinic keratosis lesion and over a 0,5 cm margin around it during sufficient time to freeze both the lesion and margin. | Drug: Cryotherapy with liquid nitrogen<br>* Topical application of liquid nitrogen spray (500ml Cry-ac ® bottle) over the actinic keratosis lesion and over a 0,5 cm margin around it during sufficient time to freeze both the lesion and margin.<br>* Other names: Cry-ac ®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rates | Clinical evaluation of treated area. | 0 months (baseline), 3 months and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogic Scale Pain Score | Pain was evaluated with a Visual Analogic Scale (blind) and a graduated scale. It was evaluated at the time 0 and 15 minutes after each intervention (Cryotherapy or PDT): at the first intervention (0 months), and at the second intervention if the residual lesion that indicates a second session (3 months). And at the third interwiew (6 months) there was no intervention, but the patients who was submitted to 2 interventions were requested about what intervention was more painfull (the first or the second one). | 0 months (baseline), 3 months, 6 months | 
| Cosmesis analysis | Cosmesis was evaluated subjetively by the patient as one of the possibilities: aesthetic outcome awfull, bad, regular, good, excellent. Cosmesis was evaluated subjetively also by the researcher as one of the possibilities: aesthetic outcome awfull, bad, regular, good, excellent. And there was and objective evaluation of cosmesis by the researcher, the presece or absence of one or more of these criteria: hypochromia, hyperpigmentation,hyperemia, scar. | 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Actinic keratosis, Photodynamic therapy, 5-aminolevulinic acid, Cryotherapy