Hydroxyapatite-toothpaste and Enamel Caries in the Primary Dentition

Tooth Diseases Clinical Trial

— ECIPDEN17  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03553966
• Other study ID #: Dr. Kurt Wolff Group
• Status: Completed
• Phase: N/A
• Start date: March 1, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: February 2020
• Source: Dr. Kurt Wolff GmbH & Co. KG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Calcium Metabolism Disorders
• Hydroxyapatite
• Tooth Decay
• Tooth Demineralization
• Tooth Diseases

Intervention

Procedure:
• Prophylactic
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.
• Cleaning teeth
Tooth Brushing F 3x daily repeated cleaning of all teeth using a standardized electric tooth brush and a fluoridated tooth paste.

Device:
• Restorative dentistry
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.

Locations

Country	Name	City	State
Poland	Poznan University of Medical Sciences, Department of Integrated Dentistry	Poznan

Sponsors (4)

Lead Sponsor	Collaborator
Dr. Kurt Wolff GmbH & Co. KG	Medical University of Bialystok, Poznan University of Medical Sciences, Wuerzburg University Hospital

Country where clinical trial is conducted

Poland, 

References & Publications (15)

Harks I, Jockel-Schneider Y, Schlagenhauf U, May TW, Gravemeier M, Prior K, Petersilka G, Ehmke B. Impact of the Daily Use of a Microcrystal Hydroxyapatite Dentifrice on De Novo Plaque Formation and Clinical/Microbiological Parameters of Periodontal Healt — View Citation

Hiller KA, Buchalla W, Grillmeier I, Neubauer C, Schmalz G. In vitro effects of hydroxyapatite containing toothpastes on dentin permeability after multiple applications and ageing. Sci Rep. 2018 Mar 20;8(1):4888. doi: 10.1038/s41598-018-22764-1. — View Citation

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) adopts Consolidated Guideline on Good Clinical Practice in the Conduct of Clinical Trials on Medicinal Products for Human Use. Int — View Citation

Ismail AI, Sohn W, Tellez M, Amaya A, Sen A, Hasson H, Pitts NB. The International Caries Detection and Assessment System (ICDAS): an integrated system for measuring dental caries. Community Dent Oral Epidemiol. 2007 Jun;35(3):170-8. — View Citation

Kensche A, Holder C, Basche S, Tahan N, Hannig C, Hannig M. Efficacy of a mouthrinse based on hydroxyapatite to reduce initial bacterial colonisation in situ. Arch Oral Biol. 2017 Aug;80:18-26. doi: 10.1016/j.archoralbio.2017.03.013. Epub 2017 Mar 23. — View Citation

Lelli M, Putignano A, Marchetti M, Foltran I, Mangani F, Procaccini M, Roveri N, Orsini G. Remineralization and repair of enamel surface by biomimetic Zn-carbonate hydroxyapatite containing toothpaste: a comparative in vivo study. Front Physiol. 2014 Sep — View Citation

Lobene RR, Weatherford T, Ross NM, Lamm RA, Menaker L. A modified gingival index for use in clinical trials. Clin Prev Dent. 1986 Jan-Feb;8(1):3-6. — View Citation

Löe H. Mechanical and chemical control of dental plaque. J Clin Periodontol. 1979 Dec;6(7):32-6. — View Citation

Luz PB, Stringhini CH, Otto BR, Port AL, Zaleski V, Oliveira RS, Pereira JT, Lussi A, Rodrigues JA. Performance of undergraduate dental students on ICDAS clinical caries detection after different learning strategies. Eur J Dent Educ. 2015 Nov;19(4):235-41 — View Citation

Milsom KM, Blinkhorn AS, Tickle M. The incidence of dental caries in the primary molar teeth of young children receiving National Health Service funded dental care in practices in the North West of England. Br Dent J. 2008 Oct 11;205(7):E14; discussion 38 — View Citation

O'Leary TJ, Drake RB, Naylor JE. The plaque control record. J Periodontol. 1972 Jan;43(1):38. — View Citation

Piaggio G, Elbourne DR, Pocock SJ, Evans SJ, Altman DG; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA. 2012 Dec 26;308(24):2594-604. doi: 10.1001/jama.2012.87802. — View Citation

REGULATION (EC) No 1223/2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 30 November 2009 on cosmetic products. (2009).

Walsh T, Worthington HV, Glenny AM, Appelbe P, Marinho VC, Shi X. Fluoride toothpastes of different concentrations for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD007868. doi: 10.1002/14651858.CD007868.pub2. Review. Update in: Cochrane Database Syst Rev. 2019 Mar 04;3:CD007868. — View Citation

World Medical Association: Declaration of Helsinki. Recommendations guiding medical physi-cians in biomedical research involving human subjects, 59th WMA General Assembly, Seoul, October, 2008

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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