Dental Caries
Conditions
Brief summary
An in situ model will be used to evaluate and compare enamel remineralization of human enamel specimens after single use of experimental children's toothpastes.
Interventions
DRUGFluoride
Fluoride Toothpaste
DRUGPlacebo
Fluoride free toothpaste
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
11 Years to 14 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males and females aged 11 to 14 inclusive who have an unstimulated salivary flow rate of at least 0.2 mL/minute and a stimulated salivary flow rate of at least 0.8 mL/minute (Screening Visit 1).
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Surface Microhardness Recovery of Test Dentifrices Relative to Placebo Dentifrice | Baseline to 4 hours | Surface microhardness recovery (SMHR) test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening while decrease in the indentation length represents rehardening of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first demineralization challenge (D1) using formula: \[(D1-R)/ (D1-B)\]\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| %SMHR of Enamel Specimens Exposed to Test Treatments | Baseline to 4 hours | Surface microhardness recovery (SMHR) test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening while decrease in the indentation length represents rehardening of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first demineralization challenge (D1) using formula: \[(D1-R)/ (D1-B)\]\*100. |
| Percent Net Acid Resistance (%NAR) of Enamel Specimens | Baseline to 4 hours | Changes in mineral content of enamel specimens exposed to dietary erosive challenge were determined by measuring the length of the indentations. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine NAR which compared the indentations values of sound enamel specimens at baseline (B), first demineralization challenge (D1) and second demineralization challenge (D2). Percent NAR was calculated by formula: \[(D1-D2)/ (D1-B)\]\*100. |
| Enamel Fluoride Uptake | Baseline to 4 hours | Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on amount of F divided by volume of the enamel cores and expressed as micrograms (μg)\* F/centimeters(cm)\^2. Difference between treatments was calculated with respect to F uptake by enamel. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Of the 70 participants screened, 15 were not randomized into the study (12 did not meet study criteria and 3 withdrew the consent). A washout fluoride (F) toothpaste was used for a week prior treatment. In-situ appliances were prepared for participants to fit enamel specimens.
Participants by arm
| Arm | Count |
|---|---|
| Overall All randomized participants who received atleast one dose of the study treatments | 55 |
| Total | 55 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 12.4 Years STANDARD_DEVIATION 1.12 |
| Race/Ethnicity, Customized Black or African American | 9 Participants |
| Race/Ethnicity, Customized More than one race | 5 Participants |
| Race/Ethnicity, Customized White | 41 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 55 | 6 / 55 | 7 / 55 | 6 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 | 0 / 55 | 0 / 55 |
Outcome results
Primary
Percentage Surface Microhardness Recovery of Test Dentifrices Relative to Placebo Dentifrice
Surface microhardness recovery (SMHR) test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening while decrease in the indentation length represents rehardening of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first demineralization challenge (D1) using formula: \[(D1-R)/ (D1-B)\]\*100.
Time frame: Baseline to 4 hours
Population: Per Protocol (PP) Population: All randomized participants who received at least one study product, had one efficacy assessment and did not have any protocol violations deemed to affect efficacy. Missing enamel specimen values were imputed, by averaging over the available enamel specimens.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1426 Ppm F) | Percentage Surface Microhardness Recovery of Test Dentifrices Relative to Placebo Dentifrice | 30.72 %SMHR | Standard Error 0.87 |
| NaF Toothpaste (1000 Ppm F) | Percentage Surface Microhardness Recovery of Test Dentifrices Relative to Placebo Dentifrice | 29.49 %SMHR | Standard Error 0.87 |
| NaF Toothpaste (500 Ppm F) | Percentage Surface Microhardness Recovery of Test Dentifrices Relative to Placebo Dentifrice | 28.29 %SMHR | Standard Error 0.87 |
| Placebo Toothpaste (0 Ppm F) | Percentage Surface Microhardness Recovery of Test Dentifrices Relative to Placebo Dentifrice | 25.13 %SMHR | Standard Error 0.87 |
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.p-value: <0.000195% CI: [3.6, 7.58]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: <0.000195% CI: [2.37, 6.35]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.002195% CI: [1.17, 5.15]ANOVA
Secondary
Enamel Fluoride Uptake
Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on amount of F divided by volume of the enamel cores and expressed as micrograms (μg)\* F/centimeters(cm)\^2. Difference between treatments was calculated with respect to F uptake by enamel.
Time frame: Baseline to 4 hours
Population: Per Protocol (PP) Population: All randomized participants who received at least one study product, had one efficacy assessment and did not have any protocol violations deemed to affect efficacy. Missing enamel specimen values were imputed, by averaging over the available enamel specimens
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1426 Ppm F) | Enamel Fluoride Uptake | 1.76 μg*F/cm^2 | Standard Error 0.08 |
| NaF Toothpaste (1000 Ppm F) | Enamel Fluoride Uptake | 1.77 μg*F/cm^2 | Standard Error 0.08 |
| NaF Toothpaste (500 Ppm F) | Enamel Fluoride Uptake | 1.47 μg*F/cm^2 | Standard Error 0.08 |
| Placebo Toothpaste (0 Ppm F) | Enamel Fluoride Uptake | 0.98 μg*F/cm^2 | Standard Error 0.08 |
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: <0.000195% CI: [0.58, 0.98]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: <0.000195% CI: [0.58, 0.99]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: <0.000195% CI: [0.29, 0.69]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.963195% CI: [-0.21, 0.2]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.004795% CI: [0.09, 0.49]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.00495% CI: [0.1, 0.5]ANOVA
Secondary
Percent Net Acid Resistance (%NAR) of Enamel Specimens
Changes in mineral content of enamel specimens exposed to dietary erosive challenge were determined by measuring the length of the indentations. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine NAR which compared the indentations values of sound enamel specimens at baseline (B), first demineralization challenge (D1) and second demineralization challenge (D2). Percent NAR was calculated by formula: \[(D1-D2)/ (D1-B)\]\*100.
Time frame: Baseline to 4 hours
Population: Per Protocol (PP) Population: All randomized participants who received at least one study product, had one efficacy assessment and did not have any protocol violations deemed to affect efficacy. Missing enamel specimen values were imputed, by averaging over the available enamel specimens.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1426 Ppm F) | Percent Net Acid Resistance (%NAR) of Enamel Specimens | -19.72 %NAR | Standard Error 1.9 |
| NaF Toothpaste (1000 Ppm F) | Percent Net Acid Resistance (%NAR) of Enamel Specimens | -19.52 %NAR | Standard Error 1.9 |
| NaF Toothpaste (500 Ppm F) | Percent Net Acid Resistance (%NAR) of Enamel Specimens | -25.82 %NAR | Standard Error 1.9 |
| Placebo Toothpaste (0 Ppm F) | Percent Net Acid Resistance (%NAR) of Enamel Specimens | -54.38 %NAR | Standard Error 1.9 |
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: <0.000195% CI: [30.07, 39.24]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: <0.000195% CI: [30.28, 39.44]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: <0.000195% CI: [23.97, 33.13]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.929295% CI: [-4.79, 4.38]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.009495% CI: [1.52, 10.69]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.007395% CI: [1.72, 10.89]ANOVA
Secondary
%SMHR of Enamel Specimens Exposed to Test Treatments
Surface microhardness recovery (SMHR) test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was determined by measuring the length of the indentations of enamel specimens. An increase in the indentation length compared to the baseline indicates softening while decrease in the indentation length represents rehardening of enamel surface. Percent SMHR was calculated from indentation values of enamel specimens at baseline (B), after in-situ hardening (R) and after first demineralization challenge (D1) using formula: \[(D1-R)/ (D1-B)\]\*100.
Time frame: Baseline to 4 hours
Population: Per Protocol (PP) Population: All randomized participants who received at least one study product, had one efficacy assessment and did not have any protocol violations deemed to affect efficacy. Missing enamel specimen values were imputed, by averaging over the available enamel specimens.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1426 Ppm F) | %SMHR of Enamel Specimens Exposed to Test Treatments | 30.72 %SMHR | Standard Error 0.87 |
| NaF Toothpaste (1000 Ppm F) | %SMHR of Enamel Specimens Exposed to Test Treatments | 29.49 %SMHR | Standard Error 0.87 |
| NaF Toothpaste (500 Ppm F) | %SMHR of Enamel Specimens Exposed to Test Treatments | 28.29 %SMHR | Standard Error 0.87 |
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.222595% CI: [-0.76, 3.22]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levels.p-value: 0.016895% CI: [0.44, 4.43]ANOVA
Comparison: Null hypothesis was no difference between treatments, being compared. Tests were 2 sided at 5% significance levelsp-value: 0.235295% CI: [-0.79, 3.19]ANOVA