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

NCT06010732 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 23-I-121
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Caries

Keywords

Caries; Remineralization; Fluoride; Dentifrice

Outcome Measures

Primary Outcomes (1)

• Percent Surface Microhardness Recovery (%SMH Recovery)

  The SMH test was 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.

  at the end of each two-week treatment per

Secondary Outcomes (6)

• Enamel Fluoride Uptake (µg F/cm2)

  at the end of each two-week treatment period

• Percent Net Acid Resistance

  at the end of each two-week treatment period

• Percentage Comparative Acid Resistance

  at the end of each two-week treatment period

• Integrated Mineral Loss (∆Z)

  at the end of each two-week treatment period

• Lesion Depth (µm)

  at the end of each two-week treatment period

Study Arms (6)

Test-Positive-Placebo

OTHER

Crossover design - Cleaning, 2-3 day non-Fluoride (F) dentifrice, Period 1 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 2 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 3 product for 2 weeks. Product sequence: 1100 ppm F as sodium fluoride Test Product,1100 ppm F as sodium fluoride (positive control) , 0 ppm F (placebo, negative control)

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

Test-Placebo-Positive

OTHER

Crossover design - Cleaning, 2-3 day non-F dentifrice, Period 1 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 2 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 3 product for 2 weeks. Product sequence: 1100 ppm F as sodium fluoride Test Product, 0 ppm F (placebo, negative control),1100 ppm F as sodium fluoride (positive control)

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

Positive-Test-Placebo

OTHER

Crossover design - Cleaning, 2-3 day non-F dentifrice, Period 1 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 2 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 3 product for 2 weeks. Product sequence: 1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product, 0 ppm F (placebo, negative control)

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

Positive-Placebo-Test

OTHER

Crossover design - Cleaning, 2-3 day non-F dentifrice, Period 1 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 2 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 3 product for 2 weeks. Product sequence: 1100 ppm F as sodium fluoride (positive control), 0 ppm F (placebo, negative control), 1100 ppm F as sodium fluoride Test Product

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

Placebo-Test-Positive

OTHER

Crossover design - Cleaning, 2-3 day non-F dentifrice, Period 1 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 2 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 3 product for 2 weeks. Product sequence: 0 ppm F (placebo, negative control), 1100 ppm F as sodium fluoride Test Product,1100 ppm F as sodium fluoride (positive control)

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

Placebo-Positive-Test

OTHER

Crossover design - Cleaning, 2-3 day non-F dentifrice, Period 1 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 2 product for 2 weeks, 4-5 day washout, cleaning, 2-3 day non-F dentifrice, Period 3 product for 2 weeks. Product sequence: 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); Drug: 1100 ppm F as sodium fluoride (positive control); Drug: 1100 ppm F as sodium fluoride Test Product

Interventions

0 ppm F (placebo, negative control) DRUG

• Each subject will use this product during one of the three treatment periods in the crossover study design.

Also known as: Tom's of Maine Silly Strawberry

Placebo-Positive-Test; Placebo-Test-Positive; Positive-Placebo-Test; Positive-Test-Placebo; Test-Placebo-Positive; Test-Positive-Placebo

1100 ppm F as sodium fluoride (positive control) DRUG

• Each subject will use this product during one of the three treatment periods in the crossover study design.

Also known as: Crest Cavity Protection Toothpaste

Placebo-Positive-Test; Placebo-Test-Positive; Positive-Placebo-Test; Positive-Test-Placebo; Test-Placebo-Positive; Test-Positive-Placebo

1100 ppm F as sodium fluoride Test Product DRUG

• Each subject will use this product during one of the three treatment periods in the crossover study design.

Also known as: Pronamel Daily Protection

Placebo-Positive-Test; Placebo-Test-Positive; Positive-Placebo-Test; Positive-Test-Placebo; Test-Placebo-Positive; Test-Positive-Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• provide voluntary, written informed consent;
• be between 18 and 85 years old;
• understand and be willing, able and likely to comply with all study procedures and restrictions;
• 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;
• be willing and capable of wearing their removable partial denture 24 hours a day for three (3), two-week treatment periods;
• 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;
• 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
• 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).

You may not qualify if:

• currently be pregnant, intending to become pregnant during the study period or breast feeding;
• currently have any medical condition that could be expected to interfere with the subject's safety during the study period;
• currently be taking antibiotics or have taken antibiotics in the two weeks prior to the beginning treatment 1;
• known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients;
• have participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or
• be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement.

Sponsors & Collaborators

• Indiana University: lead
• HALEON: collaborator

Study Sites (1)

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

Indianapolis, Indiana, 46202, United States

Location

Related Publications (17)

• 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.

  PMID: 8615941 BACKGROUND

• 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.

  PMID: 3463611 BACKGROUND

• 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.

  PMID: 6937246 BACKGROUND

• 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.

  PMID: 18285 BACKGROUND

• 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.

  PMID: 4219029 BACKGROUND

• 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.

  PMID: 23108261 BACKGROUND

• 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.

  PMID: 23082383 BACKGROUND

• 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.

  PMID: 24798979 BACKGROUND

• 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.

  PMID: 12535435 BACKGROUND

• 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.

  PMID: 1592986 BACKGROUND

• 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.

  PMID: 1592992 BACKGROUND

• 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.

  PMID: 6592201 BACKGROUND

• 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.

  PMID: 14960006 BACKGROUND

• 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.

  PMID: 20091655 BACKGROUND

• 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.

  PMID: 3471346 BACKGROUND

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

  PMID: 8615944 BACKGROUND

• 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.

  PMID: 2364403 BACKGROUND

MeSH Terms

Interventions

Sodium Fluoride; hydrated silica gel-based toothpaste

Intervention Hierarchy (Ancestors)

Fluorides; Hydrofluoric Acid; Fluorine Compounds; Inorganic Chemicals; Sodium Compounds; Cariostatic Agents; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Domenick T. Zero
• Organization: Indiana University School of Dentistry

dzero@iu.edu

3179877507

Study Officials

• Domenick Zero, DDS, MS

  Indiana University

  PRINCIPAL INVESTIGATOR

• Anderson Hara, DDS, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

• Frank Lippert, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 25, 2023
• Study Start: October 2, 2023
• Primary Completion: February 22, 2024
• Study Completion: February 22, 2024
• Last Updated: June 15, 2025
• Results First Posted: June 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)