In Situ Comparison of the Remineralization Potential of Optimized Fluoride Dentifrice With Control Fluoride Dentifrice

Caries Clinical Trial

Official title:

Comparison of the Remineralization Potential of an Optimized Fluoride Dentifrice With a Control Fluoride Dentifrice Using an in Situ Caries Model

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06010732
• Other study ID #: 23-I-121
• Status: Completed
• Phase: Phase 3
• Start date: October 2, 2023
• Est. completion date: February 22, 2024

Study information

• Verified date: April 2024
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the remineralization potential of an optimized fluoride dentifrice to a control fluoride dentifrice in an in situ caries model.

Description:

This will be a double blind, single center, 3-way crossover design study. Two to three days before the start of each treatment period the subjects will have their teeth cleaned to remove all accessible plaque and calculus and will be provided with a non-fluoride dentifrice to use until their next visit. At the beginning of each testing period, two gauze-covered 4 mm round partially demineralized bovine enamel specimens will be placed in the buccal surface of two posterior denture teeth (the specimen site may extend into the buccal flange area, if needed) of the same side of the partial denture. Once specimens are placed, subjects will wear their partial dentures twenty-four hours a day and use their assigned toothpaste twice daily, as instructed, until their next visit. Specimens will be removed after two weeks, and the subjects will undergo at least a four- to five-day washout period followed by another cleaning and two to three day lead in period. This process will be repeated until all subjects have used all three test products. Changes in the mineral content of the enamel specimens will be assessed using surface microhardness (SMH) and transverse microradiography (TMR). Enamel fluoride uptake (EFU) will be determined using the microdrill enamel biopsy technique. In addition, the net acid resistance (NAR) and the comparative acid resistance (CAR) of the demineralized enamel specimens will be determined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: February 22, 2024
• Est. primary completion date: February 8, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. provide voluntary, written informed consent;

2. be between 18 and 85 years old;

3. understand and be willing, able and likely to comply with all study procedures and restrictions;

4. be wearing a removable mandibular partial denture with sufficient room to accommodate two 4 mm round specimens in the buccal surface of two posterior denture teeth on the same side;

5. be willing and capable of wearing their removable partial denture 24 hours a day for three (3), two-week treatment periods;

6. be willing to allow study personnel to drill specimen sites in two denture teeth in the posterior section of one side of their lower partial denture, which may extend into the buccal flange area below the teeth;

7. be in good medical and dental health with no active caries or periodontal disease; NOTE: subjects presenting at screening with caries may continue in the study if their carious lesions are restored prior to beginning treatment 1; and

8. have a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate = 0.2 mL/min; gum base stimulated whole saliva flow rate = 0.8 mL/min).

Exclusion Criteria:

1. currently be pregnant, intending to become pregnant during the study period or breast feeding;

2. currently have any medical condition that could be expected to interfere with the subject's safety during the study period;

3. currently be taking antibiotics or have taken antibiotics in the two weeks prior to the beginning treatment 1;

4. known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients;

5. have participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or

6. be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement.

Related Conditions & MeSH terms

• Caries

Intervention

Drug:
• 0 ppm F (placebo, negative control)
• Each subject will use this product during one of the three treatment periods in the crossover study design.
• 1100 ppm F as sodium fluoride (positive control)
• Each subject will use this product during one of the three treatment periods in the crossover study design.
• 1100 ppm F as sodium fluoride Test Product
• Each subject will use this product during one of the three treatment periods in the crossover study design.

Locations

Country	Name	City	State
United States	Indiana University School of dentistry, Oral Health Research institute 415 Lansing Street	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	HALEON

Country where clinical trial is conducted

United States, 

References & Publications (17)

Cate JM, Arends J. Remineralization of artificial enamel lesions in vitro. Caries Res. 1977;11(5):277-86. doi: 10.1159/000260279. No abstract available. — View Citation

Clinical Aspects of De/Remineralization of Teeth. Proceedings of Models Conference 1994. Rochester, New York, June 11-14, 1994. Adv Dent Res. 1995 Nov;9(3):169-340. No abstract available. — View Citation

Corpron RE, Clark JW, Tsai A, More FG, Merrill DF, Kowalski CJ, Tice TR, Rowe CE. Intraoral effects of a fluoride-releasing device on acid-softened enamel. J Am Dent Assoc. 1986 Sep;113(3):383-8. doi: 10.14219/jada.archive.1986.0202. — View Citation

Featherstone JD, Mellberg JR. Relative rates of progress of artificial carious lesions in bovine, ovine and human enamel. Caries Res. 1981;15(1):109-14. doi: 10.1159/000260508. No abstract available. — View Citation

Koulourides T, Phantumvanit P, Munksgaard EC, Housch T. An intraoral model used for studies of fluoride incorporation in enamel. J Oral Pathol. 1974;3(4):185-96. doi: 10.1111/j.1600-0714.1974.tb01710.x. No abstract available. — View Citation

Lippert F, Butler A, Lynch RJ. Characteristics of methylcellulose acid gel lesions created in human and bovine enamel. Caries Res. 2013;47(1):50-5. doi: 10.1159/000343164. Epub 2012 Oct 25. — View Citation

Lippert F, Hara AT. Fluoride dose-response of human and bovine enamel caries lesions under remineralizing conditions. Am J Dent. 2012 Aug;25(4):205-9. — View Citation

Lippert F, Lynch RJ. Comparison of Knoop and Vickers surface microhardness and transverse microradiography for the study of early caries lesion formation in human and bovine enamel. Arch Oral Biol. 2014 Jul;59(7):704-10. doi: 10.1016/j.archoralbio.2014.04.005. Epub 2014 Apr 21. — View Citation

Marinho VC, Higgins JP, Sheiham A, Logan S. Fluoride toothpastes for preventing dental caries in children and adolescents. Cochrane Database Syst Rev. 2003;2003(1):CD002278. doi: 10.1002/14651858.CD002278. — View Citation

Mellberg JR. Hard-tissue substrates for evaluation of cariogenic and anti-cariogenic activity in situ. J Dent Res. 1992 Apr;71 Spec No:913-9. doi: 10.1177/002203459207100S25. — View Citation

Proskin HM, Chilton NW, Kingman A. Interim report of the ad hoc committee for the consideration of statistical concerns related to the use of intra-oral models in submissions for product claims approval to the American Dental Association. J Dent Res. 1992 Apr;71 Spec No:949-52. doi: 10.1177/002203459207100S31. — View Citation

Sakkab NY, Cilley WA, Haberman JP. Fluoride in deciduous teeth from an anti-caries clinical study. J Dent Res. 1984 Oct;63(10):1201-5. doi: 10.1177/00220345840630100601. — View Citation

Twetman S, Axelsson S, Dahlgren H, Holm AK, Kallestal C, Lagerlof F, Lingstrom P, Mejare I, Nordenram G, Norlund A, Petersson LG, Soder B. Caries-preventive effect of fluoride toothpaste: a systematic review. Acta Odontol Scand. 2003 Dec;61(6):347-55. doi: 10.1080/00016350310007590. — View Citation

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. — View Citation

White DJ. Use of synthetic polymer gels for artificial carious lesion preparation. Caries Res. 1987;21(3):228-42. doi: 10.1159/000261026. No abstract available. — View Citation

Zero DT, Rahbek I, Fu J, Proskin HM, Featherstone JD. Comparison of the iodide permeability test, the surface microhardness test, and mineral dissolution of bovine enamel following acid challenge. Caries Res. 1990;24(3):181-8. doi: 10.1159/000261263. — View Citation

Zero DT. In situ caries models. Adv Dent Res. 1995 Nov;9(3):214-30; discussion 231-4. doi: 10.1177/08959374950090030501. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Surface Microhardness Recovery (%SMH Recovery)	The SMH test will be used to assess changes in the mineral status of partially demineralized enamel specimens.; %SMH Recovery = (D1-R)/(D1-B) ×100 B = indentation length (µm) of sound enamel specimen at baseline D1 = indentation length (µm) after in vitro demineralization R = indentation length (µm) after intra-oral exposure.	Two weeks
Secondary	Enamel Fluoride Uptake (µg F/cm2)	The microdrill enamel biopsy technique will be used to analyze the fluoride content of the partially demineralized enamel specimens. Each enamel specimen will be mounted perpendicular to the long axis of a drill bit attached to a specially designed microdrill and drilled to a depth of ~100 µm through the entire lesion (four cores per specimen). The diameter of the drill hole will be determined using a calibrated microscope interfaced with an image analysis system. The amount of fluoride-uptake by enamel will be calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as µg F/cm2	Two weeks
Secondary	Percent Net Acid Resistance	% Net Acid Resistance = [(D1-D2) / (D1-B)] * 100 B= Indentation length (µm) of sound enamel at baseline D1= Indentation length (µm) after first in vitro demineralization D2= Indentation length (µm) after second in vitro demineralization	Two weeks
Secondary	Percentage Comparative Acid Resistance	% Comparative Acid Resistance = [(D2-R) / (D1-B)] * 100 B= Indentation length (µm) of sound enamel at baseline R= Indentation length (µm) of enamel after in situ remineralization D1= Indentation length (µm) after first in vitro demineralization D2= Indentation length (µm) after second in vitro demineralization	Two weeks
Secondary	Integrated Mineral Loss (?Z)	?Z= [(lesion depth x 87) - area under the curve*] calculated using Transverse Microradiography software program	Two weeks
Secondary	Lesion Depth (µm)	Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) determined using Transverse Microradiography software program	Two weeks
Secondary	Maximum mineral density at the surface-zone (SZmax)	SZmax will be determined using Transverse Microradiography software program	Two weeks