Evaluation of the Fluoride Dose Response Using In Situ Caries Model

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the fluoride dose response of different dentifrice fluoride concentrations - 0, 250, 1100 and 2800 ppm fluoride as sodium monofluorophosphate (MFP) and a fifth leg of 1100 ppm Stannous Fluoride (SnF2) using an in situ caries model.

Official Title
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Evaluation of the Fluoride Dose Response of MFP Dentifrice Using In Situ Caries Model

Conditions
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Caries

Intervention / Treatment
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* Drug: 0 ppm F
* Drug: 250 ppm F as MFP
* Drug: 1100 ppm as MFP
* Drug: 2800 ppm F as MFP
* Drug: 1100 ppm SnF2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be between 18 and 85 years of age; Provide written informed consent prior to participation and be given a signed copy of the informed consent form; Be in general good health as determined by the Investigator based on a review of the health history/update for participation in the trial; Be wearing a removable mandibular partial denture with sufficient room in one posterior buccal flange area to accommodate two 4 mm round enamel specimens and room on the same side to accommodate two 4 mm round specimens in the buccal surface of two posterior denture teeth; Be willing and capable of wearing their removable partial denture 24 hours a day for four (4), three-week treatment periods; Be willing to allow study personnel to drill specimen sites (as described in #iv) in their mandibular partial denture; 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); 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 being pregnant, intending to become pregnant during the study period, or breast feeding; Currently having any medical condition that could be expected to interfere with the subject's safety during the study period; Currently taking antibiotics or having taken antibiotics in the two weeks prior to beginning treatment 1; Having participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or Taking fluoride supplements, required to use a fluoride mouth rinse, or have received a professional fluoride treatment in the two weeks preceding specimen placement; Currently taking or have ever taken bisphosphonate drugs (e.g., Fosamax, Actonel and Boniva) for the treatment of osteoporosis.

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Period 1<br>0 ppm F (placebo, negative control), 250 ppm F as MFP (dose-response control), 1100 ppm F as MFP (reference), 2800 ppm F as MFP (dose-response control) | Drug: 0 ppm F<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 250 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 1100 ppm as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 2800 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>|
| Other: Period 2<br>0 ppm F (placebo, negative control), 250 ppm F as MFP (dose-response control), 1100 ppm F as MFP (reference), 2800 ppm F as MFP (dose-response control) | Drug: 0 ppm F<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 250 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 1100 ppm as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 2800 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>|
| Other: Period 3<br>0 ppm F (placebo, negative control), 250 ppm F as MFP (dose-response control), 1100 ppm F as MFP (reference), 2800 ppm F as MFP (dose-response control) | Drug: 0 ppm F<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 250 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 1100 ppm as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 2800 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>|
| Other: Period 4<br>0 ppm F (placebo, negative control), 250 ppm F as MFP (dose-response control), 1100 ppm F as MFP (reference), 2800 ppm F as MFP (dose-response control) | Drug: 0 ppm F<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 250 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 1100 ppm as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>Drug: 2800 ppm F as MFP<br>* Each subject will be randomly assigned to this treatment during one of the four periods for this crossover study.<br>|
| Other: Period 5<br>1100 ppm SnF2 toothpaste only | Drug: 1100 ppm SnF2<br>* Each subject will be assigned to this treatment during the fifth period for this crossover study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enamel Fluoride Uptake (EFU) | The EFU test will evaluate the level of fluoride in partially demineralized enamel specimens via the microdrill enamel biopsy technique by [Sakkab et al., 1984]. The calculated scores will be measured in μg F/cm2. | Evaluations will occur after 21 days of product use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enamel Fluoride Uptake (EFU) | The EFU test will evaluate the level of fluoride in partially demineralized enamel specimens via the microdrill enamel biopsy technique by [Sakkab et al., 1984]. The calculated scores will be measured in μg F/cm2. | Evaluations will occur after 7 days of product use | 
| Percent Surface Microhardness (SMH) | The SMH test will evaluate changes in the mineral status of partially demineralized enamel specimens through use of a Wilson 2100 Hardness Tester. These scores will be calculated as a percent. | Evaluations will occur after 7 days of product use | 
| Enamel Fluoride Uptake (EFU) | The EFU test will evaluate the level of fluoride in partially demineralized enamel specimens via the microdrill enamel biopsy technique by [Sakkab et al., 1984]. The calculated scores will be measured in μg F/cm2. | Evaluations will occur after 14 days of product use | 
| Percent Surface Microhardness (SMH) | The SMH test will evaluate changes in the mineral status of partially demineralized enamel specimens through use of a Wilson 2100 Hardness Tester. These scores will be calculated as a percent. | Evaluations will occur after 14 days of product use | 
| Percent Surface Microhardness (SMH) | The SMH test will evaluate changes in the mineral status of partially demineralized enamel specimens through use of a Wilson 2100 Hardness Tester. These scores will be calculated as a percent. | Evaluations will occur after 21 days of product use |