ABSTRACT Introduction Dental 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 analysis Here 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 dissemination Ethical 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 number www.clinicaltrials.gov, NCT05600517

The authors have declared no competing interest.

Trial registration number www.clinicaltrials.gov, NCT05600517

This work was supported by VR-KBF (Dnr 2019-00453) and other grants.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics approval: Dnr 2020-02533

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.