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

May 29, 2025 updated by: Domenick Zero, Indiana University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
52

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of dentistry, Oral Health Research institute 415 Lansing Street

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 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)
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 Names:
  • 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 Names:
  • 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 Names:
  • Pronamel Daily Protection
Other: 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)
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 Names:
  • 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 Names:
  • 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 Names:
  • Pronamel Daily Protection
Other: 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)
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 Names:
  • 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 Names:
  • 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 Names:
  • Pronamel Daily Protection
Other: 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
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 Names:
  • 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 Names:
  • 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 Names:
  • Pronamel Daily Protection
Other: 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)
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 Names:
  • 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 Names:
  • 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 Names:
  • Pronamel Daily Protection
Other: 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
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 Names:
  • 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 Names:
  • 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 Names:
  • Pronamel Daily Protection

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Surface Microhardness Recovery (%SMH Recovery)
Time Frame: at the end of each two-week treatment per

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Enamel Fluoride Uptake (µg F/cm2)
Time Frame: at the end of each two-week treatment period
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
at the end of each two-week treatment period
Percent Net Acid Resistance
Time Frame: at the end of each two-week treatment period
% 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
at the end of each two-week treatment period
Percentage Comparative Acid Resistance
Time Frame: at the end of each two-week treatment period
% 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
at the end of each two-week treatment period
Integrated Mineral Loss (∆Z)
Time Frame: at the end of each two-week treatment period
∆Z= [(lesion depth x 87) - area under the curve*] calculated using Transverse Microradiography software program
at the end of each two-week treatment period
Lesion Depth (µm)
Time Frame: at the end of each two-week treatment period
Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) determined using Transverse Microradiography software program
at the end of each two-week treatment period
Maximum Mineral Density at the Surface-zone (SZmax)
Time Frame: at the end of each two-week treatment period
SZmax was determined using Transverse Microradiography software program
at the end of each two-week treatment period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Indiana University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
HALEON

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Anderson Hara, DDS, PhD, Indiana University
  • Principal Investigator: Domenick Zero, DDS, MS, Indiana University
  • Principal Investigator: Frank Lippert, PhD, Indiana University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 2, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 22, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 22, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 17, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 25, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 23-I-121

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

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Sponsor/Collaborators

Locations

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