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

NCT ID: NCT06010732

Last Updated: 2025-06-15

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-02

Study Completion Date

2024-02-22

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Caries

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
double blind

Study Groups

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Test-Positive-Placebo

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)

Group Type OTHER

0 ppm F (placebo, negative control)

Intervention Type DRUG

• 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)

Intervention Type DRUG

• 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

Intervention Type DRUG

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

Test-Placebo-Positive

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)

Group Type OTHER

0 ppm F (placebo, negative control)

Intervention Type DRUG

• 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)

Intervention Type DRUG

• 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

Intervention Type DRUG

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

Positive-Test-Placebo

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)

Group Type OTHER

0 ppm F (placebo, negative control)

Intervention Type DRUG

• 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)

Intervention Type DRUG

• 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

Intervention Type DRUG

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

Positive-Placebo-Test

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

Group Type OTHER

0 ppm F (placebo, negative control)

Intervention Type DRUG

• 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)

Intervention Type DRUG

• 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

Intervention Type DRUG

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

Placebo-Test-Positive

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)

Group Type OTHER

0 ppm F (placebo, negative control)

Intervention Type DRUG

• 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)

Intervention Type DRUG

• 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

Intervention Type DRUG

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

Placebo-Positive-Test

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

Group Type OTHER

0 ppm F (placebo, negative control)

Intervention Type DRUG

• 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)

Intervention Type DRUG

• 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

Intervention Type DRUG

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

Interventions

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0 ppm F (placebo, negative control)

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

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Tom's of Maine Silly Strawberry Crest Cavity Protection Toothpaste Pronamel Daily Protection

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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HALEON

INDUSTRY

Sponsor Role collaborator

Indiana University

OTHER

Sponsor Role lead

Responsible Party

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Domenick Zero

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Domenick Zero, DDS, MS

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Anderson Hara, DDS, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Frank Lippert, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University

Locations

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

Indianapolis, Indiana, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 8615941 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3463611 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6937246 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18285 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 4219029 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23108261 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23082383 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24798979 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12535435 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1592986 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1592992 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6592201 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14960006 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20091655 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3471346 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 8615944 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2364403 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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23-I-121

Identifier Type: -

Identifier Source: org_study_id

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