This multicenter, non-inferiority trial randomized, double-blind, active controlled parallel group study evaluates the hypothesis that the home regular use of a toothpaste containing microcrystalline hydroxylapatite (HAP) (test toothpaste) provides a caries preventive effect in caries-active children with primary dentition age 3-6 which is comparable to the caries preventive effect provided by the regular use of a fluoridated tooth paste (F) (control toothpaste) over observation periods of max. 336 days. Caries development will be assessed according to the clinical criteria of the International Caries Detection and Assessment System (ICDAS).

Condition or disease:

Intervention Procedure: Tooth Brushing HAP or Procedure: Tooth Brushing F

According to the criteria of evidence based medicine the use of fluoridated tooth paste (as well as fluoridated mouth rinses) with the exception of dietary control, are the only proven measures for the prevention of dental caries. Regular tooth brushing with a fluoridated toothpaste represents the golden standard of oral care also in the primary dentition established by numerous clinical studies.

Fluorides are widely used for caries prevention. However, particularly in children and adolescents the dosage of fluorides in oral care products must be carefully monitored, as chronic overdosing of fluoride may negatively interfere with the mineralization of dentin and enamel (fluorosis). Therefore the acceptable concentration of fluorides in oral care products is limited and regulated by the European Regulation (EC) No. 12223/2009 on cosmetic products:

REGULATION (EC) No 1223/2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 30 November 2009 on cosmetic products "For any toothpaste containing 0.1 to 0.15% fluoride unless it is already labelled as contra-indicated for children (e.g. 'for adult use only') the following labelling is obligatory: 'Children of 6 years and younger: Use a pea sized amount for supervised brushing to minimize swallowing. In case of intake of fluoride from other sources consult a dentist or doctor'" Toothpastes suitable for children up to six years may only contain 500 ppm due to the risk of increased fluoride uptake by swallowing the toothpaste. However, such reduced fluoride contents may also reduce the caries prophylactic efficacy of the toothpaste particularly in highly caries-active individuals (Walsh et al. 2010). Therefore, especially for children there is a need for efficacious alternative (non-toxic) caries-preventing agents.

Target Question:

Does the regular use of a fluoride-free, microcrystalline hydroxyapatite (HAP) - containing test toothpaste have a non-inferior impact on the incidence of enamel caries in the primary dentition compared to the regular use of a fluoridated control toothpaste with proven caries preventive efficacy? The aim of this clinical trial is to assess in cohorts of caries-active children with primary teeth whether daily tooth brushing at home over observation periods of max. 336 days with a hydroxyapatite-containing toothpaste (test toothpaste) provides a protection from enamel caries development which is not inferior to the protection when brushing with a fluoridated toothpaste (control toothpaste).

Material and Methods Subjects

Study subjects will be recruited from a target population of caries-active children with primary teeth aged ≥ 3 to 6 years. The target population we be stratified according to the number of filled molars:

There will be 2 strata:

Stratum A: Children with high risk of caries development. Either 1-2 filled molars or 1-2 molars with at least ICDAS 4, which will be dentally treated. Thus, 6-7 enamel surfaces can be assessed.

Stratum B: Children with very high risk of caries development. Either 3-4 filled molars or 3-4 molars with at least ICDAS 4, which will be dentally treated. Thus, 4-5 enamel surfaces can be assessed.

Number of test centers and subjects The trial will be performed at three test centers (Poznan, Bialystok, Regensburg) Total number of subjects to be enrolled: n=200

Methods Test intervention: Oral hygiene instruction and regular domestic application of the test toothpaste (3x daily over a period of 336 days); also during weekends and holidays Reference (control) intervention: Oral hygiene instruction and regular domestic application of the fluoridated (reference) toothpaste (3x daily over a period of 336 days); also during weekends and holidays (The reference intervention corresponds to the established scientific standard for the prevention of enamel caries in primary teeth).

The following parameters will be evaluated each three months:

• caries development will be assessed according to the clinical criteria of the International Caries Detection and Assessment System (ICDAS), (Ismail et al 2007).
• changes in the coverage of the assessed primary molars with bacterial plaque according to the criteria of the Plaque Control Record.
• changes in the status of gingival health in the gingiva of the assessed primary molars according to the criteria of the Modified Gingival Index.

Inclusion Criteria:

• age 3-6 years
• complete set of fully erupted primary molars (teeth 55, 54, 64, 65, 75, 74, 84, 85)
• presence of a caries restoration (filling) on a minimum of 1 primary molar
• minimum of 4 primary molars without a restoration or fissure sealing

Exclusion Criteria:

• untreated caries lesions of ICDAS code 3-6
• known hypersensitivity to one of the ingredients of the toothpastes to be tested
• systemic disorders interfering with salivary function or flow
• regular medication intake interfering with salivary function or flow
• need for antibiotic prophylaxis during dental treatments
• participation in any other clinical study within the past 3 months or ongoing
• lack of intellectual or physical ability to conduct the study properly
• any other reason that, in the opinion of the investigator, disqualifies the subject from participating in the study

we do not plan any individual participant data available data to other researchers

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)