Evaluation of Caries Prevention Based on Genetic Etiology and Risk.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Caries,Dental

Intervention / Treatment
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* Other: Fluoride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 23 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard prevention fluoride P4+<br>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+<br>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<br>* a patient-centered education on diet, oral hygiene and fluoridated toothpaste 5000ppm with check up´s and topical fluoride application (varnish) every second month.<br>|
| No Intervention: Standard prevention fluoride P4-<br>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-<br>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<br>* a patient-centered education on diet, oral hygiene and fluoridated toothpaste 5000ppm with check up´s and topical fluoride application (varnish) every second month.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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caries, genetic, prevention, saliva, S. Mutans, lifestyle, microbiota, exposure, Proline rich protein gene 1 (PRH1), Proline rich protein gene 2 (PRH2), Deleted malignant brain tumour (DMBT-1)