An Erosion Study to Investigate the Efficacy of an Experimental Dentifrice to Remineralize Enamel

A Randomized, Examiner Blind, Crossover, in Situ Erosion Study To Investigate The Efficacy Of An Experimental Dentifrice In Remineralization Of Softened Enamel Compared To Placebo and Reference Dentifrices

The purpose of this study is to investigate the ability of an experimental dentifrice containing 1150 parts per million (ppm) fluoride to remineralize acid-softened dental enamel and help prevent further demineralization compared to a 0 ppm fluoride placebo dentifrice and a marketed, fluoride-containing dentifrice (Reference Dentifrice).

Study Overview

• Status: Completed
• Conditions: Tooth Erosion
• Intervention / Treatment: Drug: Experimental Dentifrice; Drug: Placebo Control Dentifrice; Drug: Reference Dentifrice

Detailed Description

This will be a randomized, controlled, single center, single-blind, 3 period, 3 treatment, cross-over, in situ design study. Previously demineralized bovine enamel specimens will be placed intra orally using a palatal appliance and the remineralizing performance of the experimental, reference and placebo dentifrices will be evaluated at 4 and 12 hours post toothbrushing, based on surface micro hardness measurements of the bovine enamel specimens. At each treatment visit, once the palatal the appliance is fitted in the mouth, a five minute equilibration period will ensue following which each participant will brush their teeth with their assigned product. Participants will remove the appliance for 30 minutes at 4 and 8.5 hours post brushing and will remove and store the appliance 13 hours post brushing (12 hours intraoral exposure). Sufficient participants will be screened to randomize approximately 33 participants to study treatment to ensure approximately 30 participants complete the study.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Oral Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant provision of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed.
• Participant is of either sex and any gender who, at the time of screening, is between the ages of 18-65 years, inclusive.
• Participant is willing and able to comply with scheduled visits, and other study procedures and restrictions.
• Participant is in good general and mental health with, in the opinion of the investigator or medically qualified designee, no clinically significant or relevant abnormalities in medical history or upon oral examination, or condition, that would impact the participant's safety, wellbeing or the outcome of the study, if they were to participate in the study, or affect the individual's ability to understand and follow study procedures and requirements.

• Participant with generally good oral health that fulfil all of the following:

  1. Having an unstimulated salivary flow rate of at least 0.2 milliliter per minute (mL/minute) and a stimulated salivary flow rate of at least 0.8 mL/minute.
  2. Having a maxillary dental arch suitable for the retention of the palatal appliance.
  3. Having no lesions of the oral cavity that could interfere with the study evaluations.

Exclusion Criteria:

• Participant who is an employee of the investigational site, either directly involved in the conduct of the study or a member of their immediate family; or an employee of the investigational site otherwise supervised by the investigator; or, a Haleon employee directly involved in the conduct of the study or a member of their immediate family (employees of the study site and associated academic institutes who are not directly involved in the conduct of the study are eligible to be considered as participants.)
• Participant who has participated in other studies (including non-medicinal studies) involving investigational product(s) within 30 days prior to study entry and/or during study participation.
• Participant with, in the opinion of the investigator or medically qualified designee, an acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator or medically qualified designee, would make the participant inappropriate for entry into this study.
• Participant who is pregnant (self-reported) or intending to become pregnant over the duration of the study or who is breastfeeding.
• Participant with known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients.
• A participant who, in the opinion of the investigator or medically qualified designee, can't comply with study requirements or who should not participate in the study for other reasons.
• Participant unwilling or unable to comply with the Lifestyle Considerations described in this protocol.
• Participant taking medication that may interfere significantly with the saliva flow in the judgment of the investigator. Should new medications that may interfere with the saliva flow be added, a second salivary flow test will be performed.
• Participant with any condition that would impact on their safety or wellbeing or affect their ability to understand and follow study procedures and requirements.
• Participant with any sign of grossly carious lesions (active), moderate or severe periodontal conditions, or severe tooth wear. Participant presenting at screening with minor caries may continue in the study if their carious lesions are repaired prior to the first treatment visit of the study.
• Participant who wears an oral piercing or oral appliance or orthodontia (besides participants wearing permanent lower retainers, which are eligible).
• Participant who has previously been enrolled in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Dentifrice; Participants will brush the buccal surfaces of their natural teeth using 1.5+/- 0.1 grams (g) of the experimental dentifrice containing 1150 ppm fluoride and 5 percent (%) potassium nitrate (KNO3) for 25 timed seconds and then swish the resulting dentifrice slurry around the mouth, without further brushing, for a timed period of 95 seconds. Participants will use the dentifrice under supervision of the study staff while the intraoral appliance is in place in Treatment Periods 1 to 3. There will be a washout period of a minimum of 3 days prior to each treatment during which the participants will use their own dentifrice for at least one day, and a 0 ppm fluoride washout dentifrice for two days.	Drug: Experimental Dentifrice; Dentifrice containing 1150 ppm fluoride and 5% KNO3.
Placebo Comparator: Placebo Control Dentifrice; Participants will brush the buccal surfaces of their natural teeth using 1.5+/- 0.1 g of the placebo dentifrice containing 0 ppm fluoride and 5% KNO3 for 25 timed seconds and then swish the resulting dentifrice slurry around the mouth, without further brushing, for a timed period of 95 seconds. Participants will use the dentifrice under supervision of the study staff while the intraoral appliance is in place in Treatment Periods 1 to 3. There will be a washout period of a minimum of 3 days prior to each treatment during which the participants will use their own dentifrice for at least one day, and a 0 ppm fluoride washout dentifrice for two days.	Drug: Placebo Control Dentifrice; Dentifrice containing 0 ppm fluoride and 5% KNO3.
Active Comparator: Reference Dentifrice; Participants will brush the buccal surfaces of their natural teeth using 1.5+/- 0.1 g of the reference dentifrice containing 1100 ppm fluoride as stannous fluoride (SnF2) for 25 timed seconds and then swish the resulting dentifrice slurry around the mouth, without further brushing, for a timed period of 95 seconds. Participants will use the dentifrice under supervision of the study staff while the intraoral appliance is in place in Treatment Periods 1 to 3. There will be a washout period of a minimum of 3 days prior to each treatment during which the participants will use their own dentifrice for at least one day, and a 0 ppm fluoride washout dentifrice for two days.	Drug: Reference Dentifrice; Dentifrice containing 1100 ppm fluoride as SnF2.; Other Names: Crest Pro-Health Densify Daily Protection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Percent Surface Microhardness Recovery (%SMHR) at 4 Hours (Test Dentifrice Versus (vs.) Placebo Control Dentifrice)	%SMHR was used to measure the ability of the dentifrice to remineralize enamel. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and the extent of remineralization was evaluated using surface microhardness (SMH) technique to yield the %SMHR. The enamel specimens were evaluated both prior to and after intra-oral exposure and indentation lengths were measured. The %SMHR was derived as [(E1-R)/(E1-B)] * 100 where: B = indentation length (micrometre [μm]) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), R = indentation length (μm) after 4 hours in situ remineralization.	At 4 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Percent Relative Erosion Resistance (%RER) at 4 Hours (Test Dentifrice vs. Placebo Control Dentifrice)	%RER was used to measure the ability of the dentifrice to protect enamel from further acid-induced demineralization by both acid protection and remineralization. SMH technique was used to calculate %RER. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and further treated with acid ex situ followed by additional SMH evaluations to calculate %RER. The %RER was derived as [(E1-E2)/(E1-B)] * 100 where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), E2 = indentation length (μm) after second erosive challenge (with a commercially available grapefruit juice).	At 4 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean %SMHR at 4 Hours (Test Dentifrice vs. Reference Dentifrice)	%SMHR was used to measure the ability of the dentifrice to remineralize enamel. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and the extent of remineralization was evaluated using surface SMH technique to yield the %SMHR. The enamel specimens were evaluated both prior to and after intra-oral exposure and indentation lengths were measured. The %SMHR was derived as [(E1-R)/(E1-B)] * 100 where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), R = indentation length (μm) after 4 hours in situ remineralization.	At 4 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean %SMHR at 12 Hours	%SMHR was used to measure the ability of the dentifrice to remineralize enamel. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and the extent of remineralization was evaluated using SMH technique to yield the %SMHR. The enamel specimens were evaluated both prior to and after intra-oral exposure and indentation lengths were measured. The %SMHR was derived as [(E1-R)/(E1-B)] * 100 where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), R = indentation length (μm) after 12 hours in situ remineralization.	At 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean %RER at 4 Hours (Test Dentifrice vs. Reference Dentifrice)	%RER was used to measure the ability of the dentifrice to protect enamel from further acid-induced demineralization by both acid protection and remineralization. SMH technique was used to calculate %RER. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and further treated with acid ex situ followed by additional SMH evaluations to calculate %RER. The %RER was derived as [(E1-E2)/(E1-B)] * 100 where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), E2 = indentation length (μm) after second erosive challenge (with a commercially available grapefruit juice).	At 4 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean %RER at 12 Hours	%RER was used to measure the ability of the dentifrice to protect enamel from further acid-induced demineralization by both acid protection and remineralization. SMH technique was used to calculate %RER. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and further treated with acid ex situ followed by additional SMH evaluations to calculate %RER. The %RER was derived as [(E1-E2)/(E1-B)] * 100 where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), E2 = indentation length (μm) after second erosive challenge (with a commercially available grapefruit juice).	At 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean Enamel Fluoride Uptake (EFU) at 4 and 12 Hours	EFU is a measure of how much fluoride has been incorporated into the enamel during the process of remineralization. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and chemically analyzed to measure the amount of fluoride incorporated into the enamel by the dentifrice treatment.	At 4 and 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean Acid Resistance Ratio (ARR) at 4 and 12 Hours	ARR was used to measure the resistance of the remineralized enamel to further acid softening. SMH technique was used to calculate ARR. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and further treated with acid ex situ followed by additional SMH evaluations to calculate ARR. The ARR was derived as 1 - [(E2-R)/(E1-B)] where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), E2 = indentation length (μm) after second erosive challenge (with a commercially available grapefruit juice), R = indentation length (μm) after 4 and 12 hours in situ remineralization.	At 4 and 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean %SMHR at 4 and 12 Hours (Reference Dentifrice vs Placebo Control Dentifrice)	%SMHR was used to measure the ability of the dentifrice to remineralize enamel. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatment in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and the extent of remineralization was evaluated using SMH technique to yield the %SMHR. The enamel specimens were evaluated both prior to and after intra-oral exposure and indentation lengths were measured. The %SMHR was derived as [(E1-R)/(E1-B)] * 100 where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), R = indentation length (μm) after 4 and 12 hours in situ remineralization.	At 4 and 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean %RER at 4 and 12 Hours (Reference Dentifrice vs Placebo Control Dentifrice)	%RER was used to measure the ability of the dentifrice to protect enamel from further acid-induced demineralization by both acid protection and remineralization. SMH technique was used to calculate %RER. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and further treated with acid ex situ followed by additional SMH evaluations to calculate %RER. The %RER was derived as [(E1-E2)/(E1-B)] * 100 where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), E2 = indentation length (μm) after second erosive challenge (with a commercially available grapefruit juice).	At 4 and 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean EFU at 4 and 12 Hours (Reference Dentifrice vs Placebo Control Dentifrice)	EFU is a measure of how much fluoride has been incorporated into the enamel during the process of remineralization. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and chemically analyzed to measure the amount of fluoride incorporated into the enamel by the dentifrice treatment.	At 4 and 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)
Adjusted Mean ARR at 4 and 12 Hours (Reference Dentifrice vs Placebo Control Dentifrice)	ARR was used to measure the resistance of the remineralized enamel to further acid softening. SMH technique was used to calculate ARR. Previously demineralized, sterilized bovine enamel specimens were placed intra orally using a palatal appliance. The enamel specimens were exposed to the dentifrice treatments in the mouth during the treatment application and allowed to remineralize intra orally under the action of the participant's saliva. The specimens were then removed from the palatal appliance and further treated with acid ex situ followed by additional SMH evaluations to yield ARR. The ARR was derived as 1 - [(E2-R)/(E1-B)] where: B = indentation length (μm) of sound enamel at baseline, E1 = indentation length (μm) after first erosive challenge (with a commercially available grapefruit juice), E2 = indentation length (μm) after second erosive challenge (with a commercially available grapefruit juice), R = indentation length (μm) after 4 and 12 hours in situ remineralization.	At 4 and 12 hours of intra-oral exposure following treatment on Day 1 of each treatment period (each treatment period was of 2 days with 3 days washout in between)

Collaborators and Investigators

• Sponsor: HALEON

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2024
• Primary Completion (Actual): May 7, 2024
• Study Completion (Actual): May 7, 2024

Study Registration Dates

• First Submitted: January 29, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): February 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Tooth Diseases; Tooth Demineralization; Tooth Wear; Tooth Erosion
• Other Study ID Numbers: 300057

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual participant data and study documents can be requested for further research from ww.clinical-trial-register@haleon.com
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No