Personalized oral care (Precaries): an intervention study customized according to genetic cause and risk

IntroductionDental caries is a disease that affects billions of people, and involves high and low genetic susceptibility phenotypes and different causal subtypes. The randomized clinical trial Precaries-RCT will evaluate caries prevention in adolescents, customized according to genetic cause and risk. Here we describe the Precaries-RCT and two nested Precaries studies for cost-efficient oral healthcare and personalized dentistry. Methods and analysisHere we present a basic and adaptive protocol for the Precaries-RCT multicentre caries intervention study, customized according to genetic cause and risk. It includes prescreening for high versus low genetic caries susceptibility, through self-performed sampling by mail of up to 2000 adolescents aimed for orthodontic treatment at community clinics, of which 520 are enrolled in the RCT. The participants are allocated into two groups - a high and a low genetic caries susceptibility group - that each is assigned to intensive or standard prevention. The primary outcome is % reduction in caries increment, relative to prevention and genotype, with caries outcomes measured using tactile and visual methods, bitewing radiographs, clinical photos, and quantitative laser fluorescence. The adaptive design allows for determination of incidence and progression rates and for inclusion of additional human and microbiota biomarkers and study subjects. Biological samples (e.g. swab DNA, whole and parotid saliva, and microbiota) and questionnaire data are collected. Here we also outline the nested Precaries-adolescent sample for mining of predictor and therapeutic target genes and Precaries-birth cohort samples for implementation of our findings in childhood. Ethics and disseminationEthical approval was obtained from the Swedish national board research ethics committee (Dnr 2020-02533). Informed consent will be obtained from each participant. The findings will be disseminated to the public through conference presentations and publication in peer-reviewed scientific journals. Trial registration numberwww.clinicaltrials.gov, NCT05600517 STRENGTHS AND LIMITATIONS OF THIS STUDYO_LICaries classification and prevention customized according to genetic cause and risk, and caries outcome measurements by tactile and visual methods, bitewing radiographs, clinical photos, and quantitative laser fluorescence. C_LIO_LIMulticentre study with orthodontic patients and conditions representative of the Public Dental Service clinics in Sweden, facilitating implementation, though in a part of the population. C_LIO_LIProspective study design in an orthodontic model with shortened study time and caries development on available smooth tooth surfaces. Frequent follow-up enables study termination of individuals with high caries progression, which may allow further shortening of study times, but with reduced individual data for the entire study period. C_LIO_LIConsensus-based intensified and self-care prevention in multiple repeated blocks, ensuring a high therapeutic dose; and basic and adaptive design, allowing flexible study time, caries incidence and progression outcomes, and extensive genetic profiling for online multimodal machine learning. C_LIO_LISynergizes with the Precaries-adolescence sample for mining of caries predictors and therapeutics, and Precaries-birth cohort for implementation in primary dentition/childhood. C_LI