Evaluation of Caries Prevention Based on Genetic Etiology and Risk. (PRECARIES)

Evaluation of Caries Prevention Based on Genetic Etiology and Risk: Protocol for a Multicenter Randomized Controlled and Adaptive Trial for Oral Personalized Care (PRECARIES)

Dental caries affects billions of people worldwide and involves saliva immunodeficiency, commensal pathogen and exposure (lifestyle) causal subtypes of the disease. Up to 85% of adolescents in Swedish and other low prevalence populations are caries-free while the remaining 15% show high, recurrent caries activity. Accordingly, there is a lack of cost-effective risk assessment and prevention tools for personalized oral care. This randomized adaptive clinical trial (RCT) evaluates both caries prevention based on genetic etiology and risk, as a consequence of saliva immunodeficiency genes specifying individuals as susceptible or resistant to caries, and the effect of intensified versus selfcare traditional prevention on the two groups.

Study Overview

• Status: Recruiting
• Conditions: Caries,Dental
• Intervention / Treatment: Other: Fluoride

Detailed Description

This is a protocol for a multicenter risk assessment and intervention study (PRECARIES) with an adaptive component. The study design comprises a prescreen of 2000 adolescents of which 520 will be included in the RCT study part with adolescents undergoing ordinary orthodontic treatment with multibrackets at the Public Dental Service. The orthodontic treatment allows for rapid caries development and improved discrimination between susceptible versus resistant individuals. The children are genotyped into two risk groups; genetic susceptible and non-susceptible children that are assigned to intensive or traditional standard prevention. The clinical outcomes will adaptively be measured at different time points (0, 6, 12 and months) as caries lesions at different teeth and surfaces using tactile, visual and X-ray bitewing, clinical photos and quantitative laser fluorescence (QLF). Secondary outcomes will be inflammation at the gingival margins and pocket depth at debonding of the orthodontic appliances. Questionaires are collected as well as biological samples; swab-dna, whole and parotid saliva and microbiota. Human and microbiota geno-and protein typing involves in and ex house platforms adaptively.

• Study Type: Interventional
• Enrollment (Anticipated): 520
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicklas Strömberg, Prof; Phone Number: +46733544395; Email: nicklas.stromberg@umu.se
• Study Contact Backup: Name: Anna Westerlund, Ass Prof; Phone Number: +46703171213; Email: anna.westerlund@odontologi.gu.se

Study Locations

• Sweden
  • Umeå, Sweden, 90188
    • Recruiting
    • Umeå University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 23 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- undergoing orthodontic treatment with fixed multibrackets appliance in the upper and lower arch

Exclusion Criteria:

• impacted canines
• agenesis in the frontal region
• maxillofacial surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard prevention fluoride P4+; self-care prevention on diet, oral hygiene and fluoridated toothpaste 1450 ppm with checkup every second month with one occasion of fluoride varnish at the clinic.
Experimental: Intensive prevention P4+; a patient-centered education on diet, oral hygiene and fluoridated toothpaste 5000ppm with check up´s and topical fluoride application (varnish) every second month.	Other: Fluoride; a patient-centered education on diet, oral hygiene and fluoridated toothpaste 5000ppm with check up´s and topical fluoride application (varnish) every second month.
No Intervention: Standard prevention fluoride P4-; self-care prevention on diet, oral hygiene and fluoridated toothpaste 1450 ppm with checkup every second month with one occasion of fluoride varnish at the clinic.
Experimental: Intensive prevention P4-; a patient-centered education on diet, oral hygiene and fluoridated toothpaste 5000ppm with check up´s and topical fluoride application (varnish) every second month.	Other: Fluoride; a patient-centered education on diet, oral hygiene and fluoridated toothpaste 5000ppm with check up´s and topical fluoride application (varnish) every second month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% change in increment DeFS (decayed, enamel included and filled tooth surfaces)	The % change in ΔDeFS caries increment over a follow up period of 6 and 24 months related to prevention.	6 months
% change in increment DeFS (decayed, enamel included and filled tooth surfaces)	The % change in ΔDeFS caries increment over a follow up period of 6 and 24 months related to prevention.	24 months
DFS (decayed and filled tooth surfaces) and DeFS (decayed, enamel included and filled tooth surfaces)	The baseline and prospective caries scores for incidence and progression of lesions related to risk group	Baseline (0 months)
DFS (decayed and filled tooth surfaces) and DeFS (decayed, enamel included and filled tooth surfaces)	The baseline and prospective caries scores for incidence and progression of lesions related to risk group	6 months
DFS (decayed and filled tooth surfaces) and DeFS (decayed, enamel included and filled tooth surfaces)	The baseline and prospective caries scores for incidence and progression of lesions related to risk group	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gingival inflammation	Bleeding on probing quadrant 3, Gingival inflammation will be represented by the index Bleeding on probing (BoP). BoP will be performed at the buccal surfaces in the third quadrant of the mouth approximately 21 surfaces	Baseline (0 months)
Gingival inflammation	Bleeding on probing quadrant 3, Gingival inflammation will be represented by the index Bleeding on probing (BoP). BoP will be performed at the buccal surfaces in the third quadrant of the mouth approximately 21 surfaces	6 months
Gingival inflammation	Bleeding on probing quadrant 3, Gingival inflammation will be represented by the index Bleeding on probing (BoP). BoP will be performed at the buccal surfaces in the third quadrant of the mouth approximately 21 surfaces	24 months
Mineralization disorders	Mineralization disturbances in enamel, including fluorosis, molar-incisor-hypo-mineralization, amelogenesis imperfecta are noted in the clinical examinations and by viewing clinical photographs and QLF technique.	Baseline (0 months)
Mineralization disorders	Mineralization disturbances in enamel, including fluorosis, molar-incisor-hypo-mineralization, amelogenesis imperfecta are noted in the clinical examinations and by viewing clinical photographs and QLF technique.	6 months
Mineralization disorders	Mineralization disturbances in enamel, including fluorosis, molar-incisor-hypo-mineralization, amelogenesis imperfecta are noted in the clinical examinations and by viewing clinical photographs and QLF technique.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Life style variables	Sociodemographic data (sex and ethnicity), oral hygiene, intake frequency of sweets (e.g., cookies, biscuits, ice cream or dried fruit) and sugary drinks (never, once per month, once per week, several times per week, once per day, several times per day), and the use of extra fluoride	Baseline (0 months)
Life style variables	Sociodemographic data (sex and ethnicity), oral hygiene, intake frequency of sweets (e.g., cookies, biscuits, ice cream or dried fruit) and sugary drinks (never, once per month, once per week, several times per week, once per day, several times per day), and the use of extra fluoride	24 months
Microbiota	Number and type of S. mutans	Baseline (0 months)
Microbiota	Number and type of S. mutans	24 months

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: The Swedish Research Council; Vastra Gotaland Region; Region Östergötland; Region Skane; Region Västerbotten; Region Gävleborg; Region Halland; Uppsala-Örebro Regional Research Council; County Council of Norrbotten, Sweden; Västernorrland County Council, Sweden
• Investigators: Principal Investigator: Nicklas Stromberg, Prof, Umeå University

Publications and helpful links

General Publications

• Strömberg N, Esberg A, Sheng N, Mårell L, Löfgren-Burström A, Danielsson K, Källestål C. Genetic- and Lifestyle-dependent Dental Caries Defined by the Acidic Proline-rich Protein Genes PRH1 and PRH2. EBioMedicine. 2017 Dec;26:38-46. doi: 10.1016/j.ebiom.2017.11.019. Epub 2017 Nov 22.

Helpful Links

• E Biomedicine publication

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2021
• Primary Completion (Anticipated): January 31, 2023
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): October 31, 2022

Study Record Updates

• Last Update Posted (Actual): October 31, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: genetic; prevention; caries; exposure; microbiota; lifestyle; saliva; S. Mutans; Proline rich protein gene 1 (PRH1); Proline rich protein gene 2 (PRH2); Deleted malignant brain tumour (DMBT-1)
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Demineralization; Tooth Diseases; Dental Caries; Physiological Effects of Drugs; Protective Agents; Cariostatic Agents; Fluorides
• Other Study ID Numbers: Dnr 2020-02533

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Clinical Study Report
   Information identifier: 10.1016/j.ebiom.2017.11.019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No