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

Study Overview
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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.

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

Conditions
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Caries

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Period 1<br>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)<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Tom's of Maine Silly Strawberry;Drug: 1100 ppm F as sodium fluoride (positive control)<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Crest Cavity Protection Toothpaste;Drug: 1100 ppm F as sodium fluoride Test Product<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Pronamel Daily Protection;|
| Other: Treatment Period 2<br>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)<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Tom's of Maine Silly Strawberry;Drug: 1100 ppm F as sodium fluoride (positive control)<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Crest Cavity Protection Toothpaste;Drug: 1100 ppm F as sodium fluoride Test Product<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Pronamel Daily Protection;|
| Other: Treatment Period 3<br>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)<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Tom's of Maine Silly Strawberry;Drug: 1100 ppm F as sodium fluoride (positive control)<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Crest Cavity Protection Toothpaste;Drug: 1100 ppm F as sodium fluoride Test Product<br>* • Each subject will use this product during one of the three treatment periods in the crossover study design.<br>* Other names: Pronamel Daily Protection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Surface Microhardness Recovery (%SMH Recovery) | 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. | Two weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Caries, Remineralization, Fluoride, Dentifrice