Efficacy of Topical Application of Methyl Aminolevulinate 8% and 16% Mediated by Red Light and Incubation Time of 1 and 3 Hours in the Treatment of Actinic Keratoses on the Face: A Double-Blind Randomized Controlled Clinical Protocol
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Complete remission baseline
研究概览
简要总结
The objective of this protocol is to compare the efficacy of the topical application of MAL at concentrations of 8% and 16%, mediated by red light, as well as to evaluate the impact of different incubation times (1 or 3 hours) in the treatment of actinic keratoses on the face, with a 6-month follow-up. This parallel-arm, 6-month follow-up randomized controlled clinical trial will consist of 4 groups: G1 - Control Group - MAL 16% irradiated with 643nm and 75J/cm² and 3-hour incubation time (n=36), G2 - MAL 16% and 1-hour incubation (n=36), G3 - MAL 8% - 3 hours (n=36), and G4 - MAL 8% - 1 hour (n=36). The researcher conducting the collection and the participant will be blinded to the interventions. The primary outcome will be the complete remission of the lesion at 6 months. Secondary outcomes will include treatment success (75% reduction in the initial number of lesions), recurrence rate, emergence of SCC, incidence of adverse effects, and improvement in skin texture, wrinkles, and pigmentation using a validated scale. All outcomes will be assessed at 30 days, 3, and 6 months. Quality of life will be evaluated using the Actinic Keratosis Quality of Life questionnaire (AKQoL) at 6 months.
详细描述
The multifocality of actinic keratosis, the unpredictability of lesion evolution with potential progression to squamous cell carcinoma (SCC), and the consequent risk of local extension and metastasis, alongside the recent development of new therapies, make the selection of a therapeutic regimen challenging. The increasing incidence associated economic costs, and impact on quality of life have fostered interest in studying protocols for treating this severe skin condition. The topical application of 16% methyl aminolevulinate (MAL) is well-established in the literature for its local therapeutic effects and ease of application. However, the high cost of medication, long incubation time, and adverse effects such as itching and burning in some patients limit the dissemination of this treatment. Studies are needed to test other protocols of this promising therapy to increase acceptance among patients and professionals. Therefore, the objective of this protocol is to compare the efficacy of the topical application of MAL at concentrations of 8% and 16%, mediated by red light, as well as to evaluate the impact of different incubation times (1 or 3 hours) in the treatment of actinic keratoses on the face, with a 6-month follow-up. This parallel-arm, 6-month follow-up randomized controlled clinical trial will consist of 4 groups: G1 - Control Group - MAL 16% irradiated with 643nm and 75J/cm² and 3-hour incubation time (n=36), G2 - MAL 16% and 1-hour incubation (n=36), G3 - MAL 8% - 3 hours (n=36), and G4 - MAL 8% - 1 hour (n=36). The researcher conducting the collection and the participant will be blinded to the interventions. The primary outcome will be the complete remission of the lesion at 6 months. Secondary outcomes will include treatment success (75% reduction in the initial number of lesions), recurrence rate, emergence of SCC, incidence of adverse effects, and improvement in skin texture, wrinkles, and pigmentation using a validated scale. All outcomes will be assessed at 30 days, 3, and 6 months. Quality of life will be assessed using the Actinic Keratosis Quality of Life questionnaire (AKQoL) at 6 months. If data are normal, they will be subjected to 3-way ANOVA and presented as means ± standard deviation (SD). Otherwise, they will be presented as median and interquartile range and compared using the Kruskall-Wallis and Friedman tests. Categorical variables will be evaluated with the chi-square test, Fisher's exact test, or likelihood ratio test. A p-value < 0.05 will be considered significant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Only the researcher responsible for performing the treatments (who will open the randomization envelopes) will know which treatment is assigned to each participant. The group identification will be revealed only after statistical data analysis to all involved in the study by this researcher. Therefore, the researcher responsible for data collection and their assistant will be blinded to the treatments assigned to the groups. The participant will be blinded to the type of treatment performed, as will the statistician.
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Individuals of both sexes,
- •Aged between 40 and 90 years,
- •Fitzpatrick skin phototypes I to IV,
- •Photodamaged skin with at least five clinically evident actinic keratosis lesions on the face to be treated,
- •No prior treatment for at least six months.
排除标准
- •Clinically diagnosed infiltrative lesions, as the gold standard treatment is surgical with histopathological evaluation of the lesion (surgery will be performed at no cost to the participant), who will receive guidance and referral for appropriate treatment.
- •Photosensitive diseases, such as systemic lupus erythematosus, dermatomyositis, porphyria, among others.
- •History of arsenic exposure,
- •Known allergy to MAL or similar photosensitizing agents,
- •Psychoactive drug abuse,
- •Previous radiotherapy at the lesion site(s),
- •Participation in another clinical trial,
- •Intense tanning at the time of treatment,
- •Pregnant or breastfeeding women,
- •Local or systemic infection,
- •Immunosuppression: uncompensated chronic diseases or emotional disorders considered contraindications to treatment,
- •Skin conditions on the neck and anterior chest.
研究组 & 干预措施
Experimental Group (8% MAL incubation time - 3 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: light curettage (Procedure)
Experimental Group (8% MAL incubation time - 3 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Pre irradiation of 3 hour (Other)
- Control Group (gold standard - 16% MAL with 3-hour incubation time)
Participants will be treated with 16% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: light curettage (Procedure)
- Control Group (gold standard - 16% MAL with 3-hour incubation time)
Participants will be treated with 16% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Pre irradiation of 3 hour (Other)
- Control Group (gold standard - 16% MAL with 3-hour incubation time)
Participants will be treated with 16% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: topical application of 16% methyl aminolevulinate photosensitizer (MAL) (Other)
- Control Group (gold standard - 16% MAL with 3-hour incubation time)
Participants will be treated with 16% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Visible light source (Device)
Experimental Group (16% MAL incubation time - 1 hour)
Participants will be treated with 16% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: light curettage (Procedure)
Experimental Group (16% MAL incubation time - 1 hour)
Participants will be treated with 16% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Pre irradiation of 1 hour (Other)
Experimental Group (16% MAL incubation time - 1 hour)
Participants will be treated with 16% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: topical application of 16% methyl aminolevulinate photosensitizer (MAL) (Other)
Experimental Group (16% MAL incubation time - 1 hour)
Participants will be treated with 16% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Visible light source (Device)
Experimental Group (8% MAL incubation time - 3 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: topical application of 8% methyl aminolevulinate photosensitizer MAL (Other)
Experimental Group (8% MAL incubation time - 3 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 3-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Visible light source (Device)
Experimental Group (8% MAL incubation time - 1 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: light curettage (Procedure)
Experimental Group (8% MAL incubation time - 1 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Pre irradiation of 1 hour (Other)
Experimental Group (8% MAL incubation time - 1 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: topical application of 8% methyl aminolevulinate photosensitizer MAL (Other)
Experimental Group (8% MAL incubation time - 1 hour)
Participants will be treated with 8% topical MAL photosensitizer with a 1-hour incubation period. The light source used for skin illumination will be a visible light source (LED) with a wavelength of 643nm (Hygialux LLT1601®, KLD - ANVISA registration number 10245239012).
干预措施: Visible light source (Device)
结局指标
主要结局
Complete remission baseline
时间窗: baseline
Quantitative evaluation: A count of the number of lesions with complete response, i.e., those that show total disappearance measurable after treatment, will be performed. These lesions will be clinically evaluated and the number of lesions at these periods will be compared with the initial value (baseline). Both the absolute and relative number of lesions will be considered. To avoid variability in counting, only one researcher will perform the counts.
Complete remission -30 days
时间窗: 30 days
Quantitative evaluation: A count of the number of lesions with complete response, i.e., those that show total disappearance measurable after treatment, will be performed. These lesions will be clinically evaluated and the number of lesions at these periods will be compared with the initial value (baseline). Both the absolute and relative number of lesions will be considered. To avoid variability in counting, only one researcher will perform the counts.
Complete remission - 3 months
时间窗: 3 months
Quantitative evaluation: A count of the number of lesions with complete response, i.e., those that show total disappearance measurable after treatment, will be performed. These lesions will be clinically evaluated and the number of lesions at these periods will be compared with the initial value (baseline). Both the absolute and relative number of lesions will be considered. To avoid variability in counting, only one researcher will perform the counts.
Complete remission - 6 months
时间窗: 6 months
Quantitative evaluation: A count of the number of lesions with complete response, i.e., those that show total disappearance measurable after treatment, will be performed. These lesions will be clinically evaluated and the number of lesions at these periods will be compared with the initial value (baseline). Both the absolute and relative number of lesions will be considered. To avoid variability in counting, only one researcher will perform the counts.
次要结局
- Treatment success baseline(baseline)
- Treatment success 30 days(30 days)
- Treatment success 3 months(3 months)
- Treatment success 6 months(6 months)
- Actinic keratoses recurrence rate 30 days(30 days)
- Actinic keratoses recurrence rate 3 months(3 months)
- Actinic keratoses recurrence rate 6 months(6 months)
- Prevention of squamous cell carcinoma 30 days(30 days)
- Prevention of squamous cell carcinoma 3 months(3 months)
- Prevention of squamous cell carcinoma 6 months(6 months)
- Incidence of adverse effects 30 days(30 days)
- Incidence of adverse effects 3 months(3 months)
- Incidence of adverse effects 6 months(6 months)
- Subjective pain assessment 30 days(30 days)
- Subjective pain assessment 3 months(3 months)
- Subjective pain assessment 6 months(6 months)
- Rescue medication 30 days(30 days)
- Rescue medication 3 months(3 months)
- Rescue medication 6 months(6 months)
- Evaluation of skin texture, wrinkles, and pigmentation 30 days(30 days)
- Evaluation of skin texture, wrinkles, and pigmentation 3 months(3 months)
- Evaluation of skin texture, wrinkles, and pigmentation 6 months(6 months)
- Participant satisfaction baseline(baseline)
- Participant satisfaction 30 days(30 days)
- Participant satisfaction 3 months(3 months)
- Participant satisfaction 6 months(6 months)
- Satisfaction with Facial Appearance Overall(6 months)
研究者
Anna Carolina Ratto Tempestini Horliana
PhD
University of Nove de Julho