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

Phase 3

Completed

• Conditions: Caries
• Interventions: 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

• Registration Number: NCT06010732
• Lead Sponsor: Indiana University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-08-17
• Study First Submitted QC: 2023-08-22
• Study First Posted: 2023-08-25
• Study Start: 2023-10-02
• Primary Completion: 2024-02-22
• Study Completion: 2024-02-22
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-07
• Last Update Posted: 2024-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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 to accommodate two 4 mm round specimens in the buccal surface of two posterior denture teeth on the same side;
5. be willing and capable of wearing their removable partial denture 24 hours a day for three (3), two-week treatment periods;
6. 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;
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; and
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. known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients;
5. have participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or
6. be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Period 1	1100 ppm F as sodium fluoride Test Product	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 1	0 ppm F (placebo, negative control)	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 2	1100 ppm F as sodium fluoride Test Product	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 2	0 ppm F (placebo, negative control)	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 3	1100 ppm F as sodium fluoride (positive control)	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 3	1100 ppm F as sodium fluoride Test Product	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 1	1100 ppm F as sodium fluoride (positive control)	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 2	1100 ppm F as sodium fluoride (positive control)	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product
Treatment Period 3	0 ppm F (placebo, negative control)	0 ppm F (placebo, negative control,1100 ppm F as sodium fluoride (positive control), 1100 ppm F as sodium fluoride Test Product

Primary Outcome Measures

Name	Time	Method
Percent Surface Microhardness Recovery (%SMH Recovery)	Two weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Indiana University School of dentistry, Oral Health Research institute 415 Lansing Street; 🇺🇸 Indianapolis, Indiana, United States