Double-bllind, Double-dummy, Randomized Clinical Trial Comparative Between Oral Nicotinamide Versus Topical Nicotinamide in the Management of Facial Actinic Keratosis .
Phase: PHASE1
Conditions: Actinic Keratoses
Sponsor: Federal University of Rio Grande do Sul

Title: Double-bllind, double-dummy, randomized clinical trial comparative between oral 
nicotinamide versus topical nicotinamide in the management of actinic keratosis of the face. 
Thaís Cachafeiro, MS,  Renato Marchiori Bakos, MS1 
1Universidade Fereral do Rio Grande do Sul, Programa de Pós Graduação em Ciências Médicas, 
2400 Ramiro Barcelos Avenue, Porto Alegre/RS, Brazil 90035003 
Corresponding author: 
Thaís Cachafeiro, MS 
2400 Ramiro Barcelos Avenue  
Porto Alegre/RS, Brazil 90035003 
Email: dermatologista.tc@gmail.com 
 
 
 
Conflicts of Interest: None declared. 
 
IRB approval status: Reviewed and approved by Comitê de Ética e Pesquisa da Universidade 
Federal do Rio Grande do Sul; approval # 52100621.0.0000.5347  
 
Clinicaltrials.gov  listing: NCT07049068 
 
 
16th july, 2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Protocol 
A questionnaire with the following information was completed by each participant: sex, age, 
skin type, profession, current or previous history of smoking and sun exposure history. Sun 
exposure was assessed, both current and past, as little, occasional or frequent, as well as the 
use of sunscreen. All participants were examined and evaluated for the number and location of 
facial actinic keratoses and the presence of NMSC on the entire skin by a blinded 
dermatologist.  
At all visits participants were evaluated by the same blinded dermatologist regarding number 
and location of facial actinic keratoses, and presence of NMSC on the entire skin. In follow-up 
assessments (2, 4, and 6 months), the presence of potential adverse effects of topical and 
systemic medications was assessed.  Photographs of the participants' faces were also taken at 
the initial assessment and at 6 months.  
 
Statistical analyses plan 
Continuous variables were tested for normal distribution using the Shapiro-Wilks test and 
visual assessment of the Q-Q graph. Continuous variables were described using mean and 
standard deviation when they had normal distribution (age) and median and interquartile 
range when asymmetric (number of basal actinic keratoses).  Absolute and relative frequencies 
were used for categorical variables (sex, photoprotection, phototype). The comparison of 

characteristics between groups was performed using the chi-square test for heterogeneity of 
categorical variables and Student's t-test for age. To compare the number of facial actinic 
keratoses between groups throughout the evaluations, the generalized estimating equations 
(GEE) model was used with adjustment by the Bonferroni test, considering the Tweedie 
distribution and log link function, due to the asymmetry of these variables. The following 
factors were considered for the model: group, time, and the interaction between them. 
Back-transformed estimates were performed using a paired Student's t-test in each group 
based on the logarithm data for actinic keratosis counts at each study time point compared to 
the baseline. 
The absolute difference between time points in the logarithm of actinic keratosis counts 
corresponds to the relative percentage difference between time points in the count of these 
lesions. 
 
The analyses were performed by intention to treat, using the last observation carried 
forward (LOCF) method. All participants who completed at least the 60-day assessment were 
included in the analyses. Exploratory analyses were also performed including the total number 
of study participants. 
Data were processed using IBM SPSS 25.0 version for statistical analysis and a 5% significance 
level was considered for all analyses.