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

• ClinicalTrials.gov Identifier: NCT06010732
• Recruitment Status: Completed
• First Posted: August 25, 2023
• Sponsor: Indiana University
• Collaborator: HALEON
• Information provided by (Responsible Party): Domenick Zero, Indiana University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Caries	Drug: 0 ppm F (placebo, negative control); Drug: 1100 ppm F as sodium fluoride (positive control); Drug: 1100 ppm F as sodium fluoride Test Product	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: double blind
• Primary Purpose: Prevention
• Official Title: Comparison of the Remineralization Potential of an Optimized Fluoride Dentifrice With a Control Fluoride Dentifrice Using an in Situ Caries Model
• Actual Study Start Date: October 2, 2023
• Actual Primary Completion Date: February 8, 2024
• Actual Study Completion Date: February 22, 2024

Arms and Interventions

Arm	Intervention/treatment
Treatment Period 1; 0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product	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.; Other Name: Tom's of Maine Silly Strawberry; Drug: 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.; Other Name: Crest Cavity Protection Toothpaste; Drug: 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.; Other Name: Pronamel Daily Protection
Treatment Period 2; 0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product	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.; Other Name: Tom's of Maine Silly Strawberry; Drug: 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.; Other Name: Crest Cavity Protection Toothpaste; Drug: 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.; Other Name: Pronamel Daily Protection
Treatment Period 3; 0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product	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.; Other Name: Tom's of Maine Silly Strawberry; Drug: 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.; Other Name: Crest Cavity Protection Toothpaste; Drug: 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.; Other Name: Pronamel Daily Protection

Outcome Measures

Primary Outcome Measures :

1. Percent Surface Microhardness Recovery (%SMH Recovery) [ Time Frame: Two weeks ]

   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.

Secondary Outcome Measures :

1. Enamel Fluoride Uptake (µg F/cm2) [ Time Frame: Two weeks ]
   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
2. Percent Net Acid Resistance [ Time Frame: Two weeks ]
   % 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
3. Percentage Comparative Acid Resistance [ Time Frame: Two weeks ]
   % 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
4. Integrated Mineral Loss (∆Z) [ Time Frame: Two weeks ]
   ∆Z= [(lesion depth x 87) - area under the curve*] calculated using Transverse Microradiography software program
5. Lesion Depth (µm) [ Time Frame: Two weeks ]
   Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) determined using Transverse Microradiography software program
6. Maximum mineral density at the surface-zone (SZmax) [ Time Frame: Two weeks ]
   SZmax will be determined using Transverse Microradiography software program

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Indiana

Indiana University School of dentistry, Oral Health Research institute 415 Lansing Street

Indianapolis, Indiana, United States, 46202

Sponsors and Collaborators

Indiana University

HALEON

Investigators

• Principal Investigator: Domenick Zero, DDS, MS; Indiana University
• Principal Investigator: Anderson Hara, DDS, PhD; Indiana University
• Principal Investigator: Frank Lippert, PhD; Indiana University

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

• Responsible Party: Domenick Zero, Principal Investigator, Indiana University
• ClinicalTrials.gov Identifier: NCT06010732
• Other Study ID Numbers: 23-I-121
• First Posted: August 25, 2023
• Last Update Posted: April 25, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Domenick Zero, Indiana University:

Caries; Remineralization; Fluoride; Dentifrice

Additional relevant MeSH terms:

Listerine; Fluorides; Sodium Fluoride; Cariostatic Agents; Protective Agents; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents