Evaluation of the Fluoride Dose Response of a Modified In Situ Caries Model

• Sponsor: Domenick Zero (Other)
• Overall Status: Completed
• CT.gov ID: NCT03383783
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 28
• Location: 1
• Arms: 4
• Actual Duration (Months): 4.4
• Patients Per Site Per Month: 6.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the fluoride dose response of different dentifrice fluoride concentrations - 0, 250, 500 and 1100 ppm fluoride of our existing in situ model involving the use of human enamel specimens placed in the buccal flange area of the subjects partial denture with the modified model involving placement of bovine enamel specimens in a denture tooth location.

Condition or Disease	Intervention/Treatment	Phase
Caries	Drug: 0 ppm F (placebo, negative control); Drug: 250 ppm F as NaF (dose-response control); Drug: 500 ppm F as NaF (dose-response control); Drug: 1100 ppm F as NaF (positive control)	Phase 3

Detailed Description

This will be a double blind, single center, 4-way crossover design study involving 34 adult subjects, between the ages of 18 and 85 years. 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 × 4 mm partially demineralized human enamel specimens will be placed in the buccal flange area of the subject's mandibular partial denture. In addition, two gauze-covered 4 mm round partially demineralized bovine enamel specimens will be placed in the buccal surface of two posterior denture teeth 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 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 four test products. Changes in the mineral content of the enamel specimens will be assessed using the SMH and 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 remineralized enamel specimens will be determined.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Evaluation of the Fluoride Dose Response of a Modified In Situ Caries Model
• Actual Study Start Date: Dec 19, 2017
• Actual Primary Completion Date: May 2, 2018
• Actual Study Completion Date: May 2, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Treatment Period 1 0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)	Drug: 0 ppm F (placebo, negative control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 250 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 500 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 1100 ppm F as NaF (positive control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation
Other: Treatment Period 2 0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)	Drug: 0 ppm F (placebo, negative control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 250 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 500 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 1100 ppm F as NaF (positive control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation
Other: Treatment Period 3 0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)	Drug: 0 ppm F (placebo, negative control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 250 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 500 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 1100 ppm F as NaF (positive control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation
Other: Treatment Period 4 0 ppm F (placebo, negative control), 250 ppm F as NaF (dose-response control), 500 ppm F as NaF (dose-response control), 1100 ppm F as NaF (positive control)	Drug: 0 ppm F (placebo, negative control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 250 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 500 ppm F as NaF (dose-response control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation ; Drug: 1100 ppm F as NaF (positive control); Each subject will use this product during one of the four treatment periods in the crossover study design.; Other Names: Sensodyne sodium fluoride/silica toothpaste base formulation

Outcome Measures

Primary Outcome Measures

1. Percentage Surface Microhardness Recovery (%SMH) [Enamel specimens will be evaluated after 14 days of intra-oral exposure]

   The extent of remineralization will be calculated based on the method of [Gelhard et al., 1979]. 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.

Secondary Outcome Measures

1. Net Acid Resistance (NAR) [Enamel specimens will be evaluated after 14 days of intra-oral exposure]

   The %NAR will be calculated by the method of Corpron [Corpron et al., 1986]: 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

2. Comparative Acid Resistance (CAR) [Enamel specimens will be evaluated after 14 days of intra-oral exposure]

   Using the data from the four centrally located enamel specimens, the equation used will compare explicitly the reduction in SMH brought by the first and second acid challenges: 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

3. Enamel Fluoride Uptake (EFU) [Enamel specimens will be evaluated after 14 days of intra-oral exposure]

   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.

4. Transverse Microradiography (TMR) - Integrated Mineral Loss - ∆Z [Enamel specimens will be evaluated after 14 days of intra-oral exposure]

   Lesions will be analyzed after in situ demineralization and the following three parameters calculated: Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*] Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) Maximum mineral density at the surface-zone - SZmax

5. Transverse Microradiography (TMR) - Lesion Depth - L [Enamel specimens will be evaluated after 14 days of intra-oral exposure]

   Lesions will be analyzed after in situ demineralization and the following three parameters calculated: Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*] Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) Maximum mineral density at the surface-zone - SZmax

6. Transverse Microradiography (TMR) - Maximum Mineral Density at the Surface-zone [Enamel specimens will be evaluated after 14 days of intra-oral exposure]

   Lesions will be analyzed after in situ demineralization and the following three parameters calculated: Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*] Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) Maximum mineral density at the surface-zone - SZmax (arbitrary unit from TMR software)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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 in one posterior buccal flange area to accommodate two enamel specimens (required dimensions 12 × 7 mm) and room on the same side to accommodate two 4 mm round specimens in the buccal surface of two posterior denture teeth;

5. be willing and capable of wearing their removable partial denture 24 hours a day for four (4), two-week treatment periods;

6. be willing to allow study personnel to drill specimen sites (as described #4) in their mandibular partial denture;

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.

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. have participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or

5. be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement;

6. be taking or have ever taken bisphosphonate drugs (e.g., Fosamax, Actonel and Boniva) for the treatment of osteoporosis;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University School of Dentistry, Oral Health Research Institute	Indianapolis	Indiana	United States	46202

Sponsors and Collaborators

• Domenick Zero
• GlaxoSmithKline

Investigators

• Principal Investigator: Domenick T Zero, DDS, MS, Indiana University
• Principal Investigator: Anderson Hara, DDS, PhD, Indiana University
• Principal Investigator: Frank Lippert, PhD, Indiana University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 16, 2017

More Information

Publications

None provided.

• Responsible Party: Domenick Zero, Director, Oral Health Research Institute, Indiana University
• ClinicalTrials.gov Identifier: NCT03383783
• Other Study ID Numbers: 17-I-112; 208705
• First Posted: Dec 26, 2017
• Last Update Posted: May 20, 2019
• Last Verified: May 1, 2019

• 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.: No
• Keywords provided by Domenick Zero, Director, Oral Health Research Institute, Indiana University: Caries
• Additional relevant MeSH terms: Listerine; Fluorides; Sodium Fluoride

Study Results

Participant Flow

Pre-assignment Detail	1 participant signed the informed consent and attended up to visit 2, but were dropped from the study as they no longer met inclusion criteria, and this occurred before randomization to interventions.

Arm/Group Title	All Study Participants
Arm/Group Description	This was a 4-way crossover design study. All participants were randomized to receive the following interventions: Dentifrice fluoride concentrations - 0, 250, 500 and 1100 ppm fluoride of our existing in situ model involving the use of human enamel specimens placed in the buccal flange area of the subjects partial denture with the modified model involving placement of bovine enamel specimens in a denture tooth location.
Period Title: Overall Study
STARTED	27
COMPLETED	25
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	This was a 4-way crossover design study. All participants were randomized to receive the following interventions: Dentifrice fluoride concentrations - 0, 250, 500 and 1100 ppm fluoride of our existing in situ model involving the use of human enamel specimens placed in the buccal flange area of the subjects partial denture with the modified model involving placement of bovine enamel specimens in a denture tooth location.
Overall Participants	27
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	67
Sex: Female, Male (Count of Participants)
Female	18 66.7%
Male	9 33.3%
Race/Ethnicity, Customized (Count of Participants)
White	12 44.4%
White/African-American	1 3.7%
African-American	14 51.9%
Region of Enrollment (Count of Participants)
United States	27 100%

Outcome Measures

1. Primary Outcome

Title	Percentage Surface Microhardness Recovery (%SMH)
Description	The extent of remineralization will be calculated based on the method of [Gelhard et al., 1979]. 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.
Time Frame	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bovine Specimens 0 Ppm F	Bovine Specimens 250 Ppm F	Bovine Specimens 500 Ppm F	Bovine Specimens 1100 Ppm F	Human Specimens 0 Ppm F	Human Specimens 250 Ppm F	Human Specimens 500 Ppm F	Human Specimens 1100 Ppm F
Arm/Group Description	This arm group consisted of the two bovine specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 1100 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 1100 parts per million fluoride dentifrice.
Measure Participants	27	27	27	27	27	27	27	27
Mean (95% Confidence Interval) [Percent Surface Microhardness Recovery]	13.96	30.59	40.74	48.28	7.42	16.27	21.59	26.75

2. Secondary Outcome

Title	Net Acid Resistance (NAR)
Description	The %NAR will be calculated by the method of Corpron [Corpron et al., 1986]: 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
Time Frame	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bovine Specimens 0 Ppm F	Bovine Specimens 250 Ppm F	Bovine Specimens 500 Ppm F	Bovine Specimens 1100 Ppm F	Human Specimens 0 Ppm F	Human Specimens 250 Ppm F	Human Specimens 500 Ppm F	Human Specimens 1100 Ppm F
Arm/Group Description	This arm group consisted of the two bovine specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 1100 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 1100 parts per million fluoride dentifrice.
Measure Participants	27	27	27	27	27	27	27	27
Mean (95% Confidence Interval) [% Net Acid Resistance]	-22.68	11.43	18.66	31.79	-18.60	1.99	8.31	16.87

3. Secondary Outcome

Title	Comparative Acid Resistance (CAR)
Description	Using the data from the four centrally located enamel specimens, the equation used will compare explicitly the reduction in SMH brought by the first and second acid challenges: 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
Time Frame	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bovine Specimens 0 Ppm F	Bovine Specimens 250 Ppm F	Bovine Specimens 500 Ppm F	Bovine Specimens 1100 Ppm F	Human Specimens 0 Ppm F	Human Specimens 250 Ppm F	Human Specimens 500 Ppm F	Human Specimens 1100 Ppm F
Arm/Group Description	This arm group consisted of the two bovine specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 1100 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 1100 parts per million fluoride dentifrice.
Measure Participants	27	27	27	27	27	27	27	27
Mean (95% Confidence Interval) [% Comparative Acid Resistance]	36.42	19.20	22.16	16.27	25.82	14.31	13.33	9.71

4. Secondary Outcome

Title	Enamel Fluoride Uptake (EFU)
Description	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.
Time Frame	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bovine Specimens 0 Ppm F	Bovine Specimens 250 Ppm F	Bovine Specimens 500 Ppm F	Bovine Specimens 1100 Ppm F	Human Specimens 0 Ppm F	Human Specimens 250 Ppm F	Human Specimens 500 Ppm F	Human Specimens 1100 Ppm F
Arm/Group Description	This arm group consisted of the two bovine specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 1100 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 1100 parts per million fluoride dentifrice.
Measure Participants	27	27	27	27	27	27	27	27
Mean (95% Confidence Interval) [µg F/cm^2]	0.96	2.25	2.69	2.98	0.96	2.14	2.50	2.73

5. Secondary Outcome

Title	Transverse Microradiography (TMR) - Integrated Mineral Loss - ∆Z
Description	Lesions will be analyzed after in situ demineralization and the following three parameters calculated: Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*] Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) Maximum mineral density at the surface-zone - SZmax
Time Frame	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bovine Specimens 0 Ppm F	Bovine Specimens 250 Ppm F	Bovine Specimens 500 Ppm F	Bovine Specimens 1100 Ppm F	Human Specimens 0 Ppm F	Human Specimens 250 Ppm F	Human Specimens 500 Ppm F	Human Specimens 1100 Ppm F
Arm/Group Description	This arm group consisted of the two bovine specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 1100 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 1100 parts per million fluoride dentifrice.
Measure Participants	27	27	27	27	27	27	27	27
Mean (95% Confidence Interval) [Integrated Mineral Loss - ∆Z]	1240	902	664	684	1526	912	901	859

6. Secondary Outcome

Title	Transverse Microradiography (TMR) - Lesion Depth - L
Description	Lesions will be analyzed after in situ demineralization and the following three parameters calculated: Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*] Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) Maximum mineral density at the surface-zone - SZmax
Time Frame	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bovine Specimens 0 Ppm F	Bovine Specimens 250 Ppm F	Bovine Specimens 500 Ppm F	Bovine Specimens 1100 Ppm F	Human Specimens 0 Ppm F	Human Specimens 250 Ppm F	Human Specimens 500 Ppm F	Human Specimens 1100 Ppm F
Arm/Group Description	This arm group consisted of the two bovine specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 1100 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 1100 parts per million fluoride dentifrice.
Measure Participants	27	27	27	27	27	27	27	27
Mean (95% Confidence Interval) [Micrometers]	52.01	41.74	34.85	27.31	60.73	42.12	37.38	36.02

7. Secondary Outcome

Title	Transverse Microradiography (TMR) - Maximum Mineral Density at the Surface-zone
Description	Lesions will be analyzed after in situ demineralization and the following three parameters calculated: Integrated Mineral Loss - ∆Z= [(lesion depth x 87) - area under the curve*] Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) Maximum mineral density at the surface-zone - SZmax (arbitrary unit from TMR software)
Time Frame	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bovine Specimens 0 Ppm F	Bovine Specimens 250 Ppm F	Bovine Specimens 500 Ppm F	Bovine Specimens 1100 Ppm F	Human Specimens 0 Ppm F	Human Specimens 250 Ppm F	Human Specimens 500 Ppm F	Human Specimens 1100 Ppm F
Arm/Group Description	This arm group consisted of the two bovine specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two bovine specimens and 1100 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 0 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 250 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 500 parts per million fluoride dentifrice.	This arm group consisted of the two human specimens and 1100 parts per million fluoride dentifrice.
Measure Participants	27	27	27	27	27	27	27	27
Mean (95% Confidence Interval) [SZmax]	62.17	62.54	67.13	65.93	61.22	62.99	61.38	63.66

Adverse Events

Time Frame	Each participant was monitored for a 3 month period.
Adverse Event Reporting Description	The collection/monitoring of adverse events started at visit 2 (prior to randomization), at which time there were 28 eligible subjects. Human and bovine specimens were both placed on the same side of the lower partial dentures in 27 subjects at visit 3 (randomization), and from that point forward adverse events were monitored based on the assigned treatment.
Arm/Group Title	0 Ppm F		250 Ppm F		500 Ppm F		1100 Ppm F		Between Treatment Periods		Prior to Randomization
Arm/Group Description	0 parts per million fluoride		250 parts per million fluoride		500 parts per million fluoride		1100 parts per million fluoride		Adverse Events that occurred between treatment periods.		Adverse Events that occurred prior to a subject being randomized into the study.
All Cause Mortality
	0 Ppm F		250 Ppm F		500 Ppm F		1100 Ppm F		Between Treatment Periods		Prior to Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)		0/27 (0%)		0/27 (0%)		0/27 (0%)		0/28 (0%)
Serious Adverse Events
	0 Ppm F		250 Ppm F		500 Ppm F		1100 Ppm F		Between Treatment Periods		Prior to Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/27 (0%)		0/27 (0%)		0/27 (0%)		0/27 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	0 Ppm F		250 Ppm F		500 Ppm F		1100 Ppm F		Between Treatment Periods		Prior to Randomization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/27 (37%)		5/27 (18.5%)		6/27 (22.2%)		5/27 (18.5%)		7/27 (25.9%)		18/28 (64.3%)
Eye disorders
Dry Eyes	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/28 (0%)	0
Gastrointestinal disorders
Mouth Erythema	1/27 (3.7%)	1	2/27 (7.4%)	3	4/27 (14.8%)	4	3/27 (11.1%)	4	0/27 (0%)	0	5/28 (17.9%)	5
Cavity	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Diarrhea	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/28 (0%)	0
Gum Tenderness	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Loose Crown	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Lost Filling	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Mouth Ulceration	2/27 (7.4%)	2	2/27 (7.4%)	5	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Mucosal White Patch	0/27 (0%)	0	1/27 (3.7%)	1	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Oral Burning Sensation	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	1/27 (3.7%)	1	0/27 (0%)	0	0/28 (0%)	0
Tooth Extraction	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Vomiting	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Infections and infestations
Common Cold	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	1/28 (3.6%)	1
Enlarged Lymphnode	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Fever	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Infected Cysts	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	2	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Influenza	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/28 (0%)	0
Sinus Infection	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Swollen Eye Lid	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/28 (0%)	0
Tooth Infection	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/28 (0%)	0
Injury, poisoning and procedural complications
Back Pain	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/28 (0%)	0
Head Contusion	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Hip Pain	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/28 (0%)	0
Leg Cramps	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Muscle Stiffness	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Neck Pain	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Shoulder Pain	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Nervous system disorders
Syncope	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Coughing	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Nasal Congestion	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Nasal Epitaxis	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Sinus Congestion	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/28 (0%)	0
Sinus Headache	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1
Sore Throat	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/28 (0%)	0
Skin and subcutaneous tissue disorders
Skin Keratosis	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/27 (3.7%)	1	0/28 (0%)	0
Vascular disorders
Hypertension	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0	1/28 (3.6%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.