Hydroxyapatite-toothpaste and Enamel Caries in the Primary Dentition

Study Overview
=================
Brief Summary
-----------------
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

Detailed Description
-----------------
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.

Official Title
-----------------
Impact of the Daily Use of Hydroxyapatite-toothpaste on the Occurrence of Enamel Caries in the Primary Dentition (ECIPDEN17)

Conditions
-----------------
Tooth Decay, Hydroxyapatite, Tooth Demineralization, Tooth Diseases

Intervention / Treatment
-----------------
* Procedure: Prophylactic
* Procedure: Cleaning teeth
* Device: Restorative dentistry


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 3 Years
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, double-blind, randomized, active-controlled parallel-group study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tooth Brushing HAP+Restorative dentistry<br>Arm Intervention: HA-Toothpaste Tooth Brushing HA Prophylactic cleaning of all teeth using a standardized electric tooth brush and a non-fluoridated toothpaste containing microcrystalline hydroxylapatite 3x daily over the duration of the study (336 days). Procedure: Tooth Brushing HA | Procedure: Prophylactic<br>* Tooth Brushing HA 3x daily repeated cleaning of all teeth using a standardized electric tooth brush and a non-fluoridated tooth paste containing microcrystalline hydroxylapatite.<br>* Other names: ECIPDEN17;Device: Restorative dentistry<br>* If in a subject a significant increase of carious lesions will be observed, her/his parents are informed about the necessity for further caries preventive measures (e.g. dietary changes, use of fluoride products, reduction of cariogenic microflora with chlorhexidine, xylitol chewing gum, etc.) and caries preventive treatment (removing caries and placing a restoration) by the study centers is offered.<br>|
| Active Comparator: Tooth Brushing F+Restorative dentistry<br>Cleaning teeth using a standardized electric tooth brush and a fluoridated tooth paste containing amino fluoride (500 ppm F-), (three times daily over the duration of the study (336 days). Intervention: Procedure: Tooth Brushing F 3x daily repeated cleaning of all teeth using a standardized electric tooth brush and a fluoridated toothpaste. | Procedure: Cleaning teeth<br>* Tooth Brushing F 3x daily repeated cleaning of all teeth using a standardized electric tooth brush and a fluoridated tooth paste.<br>* Other names: ECIPDEN17;Device: Restorative dentistry<br>* If in a subject a significant increase of carious lesions will be observed, her/his parents are informed about the necessity for further caries preventive measures (e.g. dietary changes, use of fluoride products, reduction of cariogenic microflora with chlorhexidine, xylitol chewing gum, etc.) and caries preventive treatment (removing caries and placing a restoration) by the study centers is offered.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of study subjects experiencing new enamel caries lesions (≥ ICDAS code 1) | Percentage of study subjects experiencing the new development of at least one enamel caries lesions ≥ ICDAS code 1 or the progression of an existing enamel caries lesion by at least one ICDAS code on any of the evaluated primary molars during the observation period of 336 days. Reference: ICDAS II code (International Caries Detection and Assessment System; ICDAS); Ismail et al. 2007. | 336 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gingival Inflammation using the Gingival Index | Changes in the status of gingival health in the gingiva of the assessed primary molars according to the criteria of the Modified Gingival Index.. | 336 days | 
| Plaque Coverage using the Plaque Control Record | Changes in the coverage of the assessed primary molars with bacterial plaque according to the criteria of the Plaque Control Record. | 336 days | 
| Percentage of study subjects experiencing new enamel caries lesions (≥ ICDAS code 2) | Percentage of study subjects experiencing the new development of at least one enamel caries lesions ≥ ICDAS code 2 during the observation period (336 days). | 336 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dental caries, Toothpaste, Fluoride, Hydroxyapatite