Caries
Conditions
Keywords
Caries, Remineralization, Fluoride, Dentifrice
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.
Interventions
• Each subject will use this product during one of the three treatment periods in the crossover study design.
DRUG1100 ppm F as sodium fluoride (positive control)
• Each subject will use this product during one of the three treatment periods in the crossover study design.
DRUG1100 ppm F as sodium fluoride Test Product
• Each subject will use this product during one of the three treatment periods in the crossover study design.
Sponsors
HALEON
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
double blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
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 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Surface Microhardness Recovery (%SMH Recovery) | at the end of each two-week treatment per | The SMH test was 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
| Measure | Time frame | Description |
|---|---|---|
| Enamel Fluoride Uptake (µg F/cm2) | at the end of each two-week treatment period | 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 | at the end of each two-week treatment period | % 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 |
| Percentage Comparative Acid Resistance | at the end of each two-week treatment period | % 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 |
| Integrated Mineral Loss (∆Z) | at the end of each two-week treatment period | ∆Z= \[(lesion depth x 87) - area under the curve\*\] calculated using Transverse Microradiography software program |
| Lesion Depth (µm) | at the end of each two-week treatment period | Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) determined using Transverse Microradiography software program |
| Maximum Mineral Density at the Surface-zone (SZmax) | at the end of each two-week treatment period | SZmax was determined using Transverse Microradiography software program |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants This was a three-way crossover design:
0 ppm F (placebo, negative control;1100 ppm F as sodium fluoride (positive control); 1100 ppm F as sodium fluoride Test Product | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Crossover Period 1 | Protocol Violation | 0 | 0 | 1 | 0 | 1 | 0 |
| Crossover Period 2 | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Crossover Period 2 | broken denture | 0 | 0 | 1 | 0 | 0 | 0 |
| Washout Between Periods 1 and 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 70 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 52 | 0 / 52 |
| other Total, other adverse events | 23 / 52 | 16 / 52 | 19 / 52 |
| serious Total, serious adverse events | 1 / 52 | 0 / 52 | 1 / 52 |
Outcome results
Primary
Percent Surface Microhardness Recovery (%SMH Recovery)
The SMH test was 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.
Time frame: at the end of each two-week treatment per
Population: Analyses were performed using all available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0 Ppm F (Placebo) | Percent Surface Microhardness Recovery (%SMH Recovery) | 24.4 Percent Surface Microhardness Recovery |
| 1100 Ppm F as Sodium Fluoride (Positive Control) | Percent Surface Microhardness Recovery (%SMH Recovery) | 51.6 Percent Surface Microhardness Recovery |
| 1100 Ppm F as Sodium Fluoride Test Product | Percent Surface Microhardness Recovery (%SMH Recovery) | 51.5 Percent Surface Microhardness Recovery |
Comparison: Based on previous studies we estimate the standard deviation of the differences between treatments in the crossover model to be 20 for % SMH recovery. With a sample size of 58 subjects completing the study, the study had 80% power to detect a difference between any two treatments of 7.5 for % SMH recovery, assuming two-sided tests each conducted at a 5% significance level.p-value: 0.98695% CI: [-5.5, 5.4]Mixed Models Analysis
Comparison: Based on previous studies we estimate the standard deviation of the differences between treatments in the crossover model to be 20 for % SMH recovery. With a sample size of 58 subjects completing the study, the study had 80% power to detect a difference between any two treatments of 7.5 for % SMH recovery, assuming two-sided tests each conducted at a 5% significance level.p-value: <0.00195% CI: [21.7, 32.6]Mixed Models Analysis
Comparison: Based on previous studies we estimate the standard deviation of the differences between treatments in the crossover model to be 20 for % SMH recovery. With a sample size of 58 subjects completing the study, the study had 80% power to detect a difference between any two treatments of 7.5 for % SMH recovery, assuming two-sided tests each conducted at a 5% significance level.p-value: <0.00195% CI: [21.7, 32.7]Mixed Models Analysis
Secondary
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
Time frame: at the end of each two-week treatment period
Population: Analyses were performed using all available data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 0 Ppm F (Placebo) | Enamel Fluoride Uptake (µg F/cm2) | 1.99 µg F/cm2 |
| 1100 Ppm F as Sodium Fluoride (Positive Control) | Enamel Fluoride Uptake (µg F/cm2) | 10.32 µg F/cm2 |
| 1100 Ppm F as Sodium Fluoride Test Product | Enamel Fluoride Uptake (µg F/cm2) | 11.45 µg F/cm2 |
Comparison: analyzed as log(EFU)p-value: 0.2395% CI: [0.93, 1.32]Mixed Models Analysis
Comparison: analyzed as log(EFU)p-value: <0.00195% CI: [4.86, 6.85]Mixed Models Analysis
Comparison: analyzed as log(EFU)p-value: <0.00195% CI: [4.37, 6.18]Mixed Models Analysis
Secondary
Integrated Mineral Loss (∆Z)
∆Z= \[(lesion depth x 87) - area under the curve\*\] calculated using Transverse Microradiography software program
Time frame: at the end of each two-week treatment period
Population: Analyses were performed using all available data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 0 Ppm F (Placebo) | Integrated Mineral Loss (∆Z) | 998 Integrated Mineral Loss (∆Z) |
| 1100 Ppm F as Sodium Fluoride (Positive Control) | Integrated Mineral Loss (∆Z) | 703 Integrated Mineral Loss (∆Z) |
| 1100 Ppm F as Sodium Fluoride Test Product | Integrated Mineral Loss (∆Z) | 708 Integrated Mineral Loss (∆Z) |
Comparison: analyzed as log(∆Z)p-value: 0.90595% CI: [0.9, 1.13]Mixed Models Analysis
Comparison: analyzed as log(∆Z)p-value: <0.00195% CI: [0.63, 0.8]Mixed Models Analysis
Comparison: analyzed as log(∆Z)p-value: <0.00195% CI: [0.63, 0.79]Mixed Models Analysis
Secondary
Lesion Depth (µm)
Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) determined using Transverse Microradiography software program
Time frame: at the end of each two-week treatment period
Population: Analyses were performed using all available data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 0 Ppm F (Placebo) | Lesion Depth (µm) | 40.5 µm |
| 1100 Ppm F as Sodium Fluoride (Positive Control) | Lesion Depth (µm) | 31.2 µm |
| 1100 Ppm F as Sodium Fluoride Test Product | Lesion Depth (µm) | 30.6 µm |
Comparison: analyzed as log(lesion depth)p-value: 0.72195% CI: [0.88, 1.09]Mixed Models Analysis
Comparison: analyzed as log(lesion depth)p-value: <0.00195% CI: [0.68, 0.84]Mixed Models Analysis
Comparison: analyzed as log(lesion depth)p-value: <0.00195% CI: [0.69, 0.86]Mixed Models Analysis
Secondary
Maximum Mineral Density at the Surface-zone (SZmax)
SZmax was determined using Transverse Microradiography software program
Time frame: at the end of each two-week treatment period
Population: Analyses were performed using all available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0 Ppm F (Placebo) | Maximum Mineral Density at the Surface-zone (SZmax) | 59.26 Maximum mineral density at the surface-z |
| 1100 Ppm F as Sodium Fluoride (Positive Control) | Maximum Mineral Density at the Surface-zone (SZmax) | 66.17 Maximum mineral density at the surface-z |
| 1100 Ppm F as Sodium Fluoride Test Product | Maximum Mineral Density at the Surface-zone (SZmax) | 65.61 Maximum mineral density at the surface-z |
p-value: 0.64795% CI: [-2.95, 1.84]Mixed Models Analysis
p-value: <0.00195% CI: [3.95, 8.75]Mixed Models Analysis
p-value: <0.00195% CI: [4.49, 9.31]Mixed Models Analysis
Secondary
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
Time frame: at the end of each two-week treatment period
Population: Analyses were performed using all available data.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| 0 Ppm F (Placebo) | Percentage Comparative Acid Resistance | 20.27 Percentage Comparative Acid Resistance |
| 1100 Ppm F as Sodium Fluoride (Positive Control) | Percentage Comparative Acid Resistance | 16.40 Percentage Comparative Acid Resistance |
| 1100 Ppm F as Sodium Fluoride Test Product | Percentage Comparative Acid Resistance | 13.51 Percentage Comparative Acid Resistance |
Comparison: analyzed as log(%CAR+100)p-value: 0.19195% CI: [0.93, 1.32]Mixed Models Analysis
Comparison: analyzed as log(%CAR+100)p-value: 0.00395% CI: [0.91, 0.98]Mixed Models Analysis
Comparison: analyzed as log(%CAR+100)p-value: 0.09295% CI: [0.93, 1.01]Mixed Models Analysis
Secondary
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
Time frame: at the end of each two-week treatment period
Population: Analyses were performed using all available data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 0 Ppm F (Placebo) | Percent Net Acid Resistance | 2.6 Percent Net Acid Resistance |
| 1100 Ppm F as Sodium Fluoride (Positive Control) | Percent Net Acid Resistance | 34.3 Percent Net Acid Resistance |
| 1100 Ppm F as Sodium Fluoride Test Product | Percent Net Acid Resistance | 37.4 Percent Net Acid Resistance |
p-value: 0.27295% CI: [-2.5, 8.6]Mixed Models Analysis
p-value: <0.00195% CI: [29.3, 40.3]Mixed Models Analysis
p-value: <0.00195% CI: [26.2, 37.3]Mixed Models Analysis