Enamel Erosion
Conditions
Brief summary
The proposed study will evaluate the performance of fluoride delivered from a new dentifrice formulation without potassium nitrate. It will also evaluate the dose-response to fluoride by testing four dentifrices covering a range of sodium fluoride concentration.
Interventions
DRUGsodium fluoride
fluoride as sodium fluoride
DRUGno added fluoride in a silica base
no added fluoride
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* intact maxillary dental arch suitable to retain a palatal appliance, an intact mandibular dental arch and a stimulated/unstimulated saliva flow rate of ≥ 0.8 milliliter/minute (ml/min) and ≥ 0.2 ml/min respectively.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Surface Microhardness Recovery (%SMHR) Dose Response Relationship | Baseline to 4 hours | 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 erosive challenge (E1) using formula: \[(E1-R)/ (E1-B)\]\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| %SMHR | Baseline to 4 hours | 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 erosive challenge (E1) using formula: \[(E1-R)/ (E1-B)\]\*100. |
| Percentage Relative Erosion Resistance | 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 relative erosion resistance which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent relative erosion resistance was calculated by formula: \[(E1-E2)/ (E1-B)\]\*100. |
| Enamel Fluoride Uptake (Corrected Data) | 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 fluoride divided by area of the enamel cores. Data analysis was based on corrected data. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
A total of 72 participants were screened, and 62 were randomized into the study. 9 participants did not meet the study criteria and 1 withdrew consent. A washout non-fluoridated toothpaste was used for 2 days prior treatment. In-situ appliances were prepared for participants to fit enamel specimens.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants who received at least one dose of the study treatments. | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period II | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Period III | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 36.7 Years STANDARD_DEVIATION 12.2 |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 27 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 | 3 / 62 | 6 / 61 | 1 / 62 | 4 / 60 |
| serious Total, serious adverse events | 0 / 62 | 0 / 61 | 0 / 62 | 0 / 60 |
Outcome results
Primary
Percentage Surface Microhardness Recovery (%SMHR) Dose Response Relationship
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 erosive challenge (E1) using formula: \[(E1-R)/ (E1-B)\]\*100.
Time frame: Baseline to 4 hours
Population: Per protocol 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 values were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Dentifrice (1426 ppmF) | Percentage Surface Microhardness Recovery (%SMHR) Dose Response Relationship | 30.89 %SMHR | Standard Error 1.38 |
| NaF Dentifrice (1150 ppmF) | Percentage Surface Microhardness Recovery (%SMHR) Dose Response Relationship | 28.71 %SMHR | Standard Error 1.38 |
| NaF Dentifrice (250 ppmF) | Percentage Surface Microhardness Recovery (%SMHR) Dose Response Relationship | 25.28 %SMHR | Standard Error 1.38 |
| Placebo Dentifrice (0 ppmF) | Percentage Surface Microhardness Recovery (%SMHR) Dose Response Relationship | 21.03 %SMHR | Standard Error 1.39 |
Comparison: Test for linear dose-response relationship was performed for %SMHR as a function of fluoride concentration.p-value: <0.0001ANOVA
Comparison: Test for quadratic dose-response relationship was performed for %SMHR as a function of fluoride concentration.p-value: 0.3748ANOVA
Secondary
Enamel Fluoride Uptake (Corrected Data)
Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on amount of fluoride divided by area of the enamel cores. Data analysis was based on corrected data.
Time frame: Baseline to 4 hours
Population: 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 values were not imputed. Data analysis for this outcome measure was performed based on a correction factor.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Dentifrice (1426 ppmF) | Enamel Fluoride Uptake (Corrected Data) | 3.13 micrograms*F/centimeters^2 | Standard Error 0.09 |
| NaF Dentifrice (1150 ppmF) | Enamel Fluoride Uptake (Corrected Data) | 3.07 micrograms*F/centimeters^2 | Standard Error 0.09 |
| NaF Dentifrice (250 ppmF) | Enamel Fluoride Uptake (Corrected Data) | 2.09 micrograms*F/centimeters^2 | Standard Error 0.09 |
| Placebo Dentifrice (0 ppmF) | Enamel Fluoride Uptake (Corrected Data) | 1.47 micrograms*F/centimeters^2 | Standard Error 0.09 |
Comparison: Test for linear dose-response relationship was performed for EFU as a function of fluoride concentration.p-value: <0.0001ANOVA
Comparison: Test for quadratic dose-response relationship was performed for EFU as a function of fluoride concentration.p-value: 0.0008ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [1.42, 1.9]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [1.36, 1.85]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [0.38, 0.86]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: 0.66895% CI: [-0.19, 0.29]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [0.8, 1.28]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [0.75, 1.23]ANOVA
Secondary
Percentage Relative Erosion Resistance
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 relative erosion resistance which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent relative erosion resistance was calculated by formula: \[(E1-E2)/ (E1-B)\]\*100.
Time frame: Baseline to 4 hours
Population: 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 values were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Dentifrice (1426 ppmF) | Percentage Relative Erosion Resistance | -38.83 % Relative Erosion Resistance | Standard Error 2.75 |
| NaF Dentifrice (1150 ppmF) | Percentage Relative Erosion Resistance | -39.75 % Relative Erosion Resistance | Standard Error 2.75 |
| NaF Dentifrice (250 ppmF) | Percentage Relative Erosion Resistance | -50.40 % Relative Erosion Resistance | Standard Error 2.75 |
| Placebo Dentifrice (0 ppmF) | Percentage Relative Erosion Resistance | -71.21 % Relative Erosion Resistance | Standard Error 2.77 |
Comparison: Test for linear dose-response relationship was performed for %RER as a function of fluoride concentration.p-value: <0.0001ANOVA
Comparison: Test for quadratic dose-response relationship was performed for %RER as a function of fluoride concentration.p-value: 0.0002ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [25.18, 39.59]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [24.25, 38.67]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: <0.000195% CI: [13.6, 28.02]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: 0.895% CI: [-6.25, 8.1]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: 0.001795% CI: [4.4, 18.74]ANOVA
Comparison: Null hypothesis considered no difference between treatments, being compared.p-value: 0.003895% CI: [3.48, 17.81]ANOVA
Secondary
%SMHR
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 erosive challenge (E1) using formula: \[(E1-R)/ (E1-B)\]\*100.
Time frame: Baseline to 4 hours
Population: 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 values were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Dentifrice (1426 ppmF) | %SMHR | 30.9 %SMHR | Standard Error 1.38 |
| NaF Dentifrice (1150 ppmF) | %SMHR | 28.7 %SMHR | Standard Error 1.38 |
| NaF Dentifrice (250 ppmF) | %SMHR | 25.3 %SMHR | Standard Error 1.38 |
| Placebo Dentifrice (0 ppmF) | %SMHR | 21.0 %SMHR | Standard Error 1.39 |
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: 0.189895% CI: [-1.09, 5.43]ANOVA
Comparison: Null hypothesis considered no dose-response relationship between %SMHR and fluoride concentration in the dentifrice.p-value: 0.000995% CI: [2.35, 8.86]ANOVA
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: 0.038995% CI: [0.18, 6.68]ANOVA
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: <0.000195% CI: [6.58, 13.13]ANOVA
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: <0.000195% CI: [4.41, 10.96]ANOVA
Comparison: Null hypothesis considered treatments in comparison to be equal.p-value: 0.011295% CI: [0.98, 7.53]ANOVA