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

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.

Study Overview

• Status: Completed
• Conditions: Caries
• Intervention / Treatment: 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)

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 Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Dentistry, Oral Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

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 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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Surface Microhardness Recovery (%SMH)	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.	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net Acid Resistance (NAR)	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	Enamel specimens will be evaluated after 14 days of intra-oral exposure
Comparative Acid Resistance (CAR)	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	Enamel specimens will be evaluated after 14 days of intra-oral exposure
Enamel Fluoride Uptake (EFU)	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.	Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Integrated Mineral Loss - ∆Z	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	Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Lesion Depth - L	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	Enamel specimens will be evaluated after 14 days of intra-oral exposure
Transverse Microradiography (TMR) - Maximum Mineral Density at the Surface-zone	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)	Enamel specimens will be evaluated after 14 days of intra-oral exposure

Collaborators and Investigators

• Sponsor: Domenick Zero
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Anderson Hara, DDS, PhD, Indiana University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 19, 2017
• Primary Completion (ACTUAL): May 2, 2018
• Study Completion (ACTUAL): May 2, 2018

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: December 22, 2017
• First Posted (ACTUAL): December 26, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 20, 2019
• Last Update Submitted That Met QC Criteria: May 16, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Caries
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Protective Agents; Cariostatic Agents; Listerine; Fluorides; Sodium Fluoride
• Other Study ID Numbers: 17-I-112; 208705 (OTHER: GlaxoSmithKline)

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.: No