Dental Erosion, Acid Wear
Conditions
Brief summary
The purpose of this study is to compare and evaluate the ability of two European Union (EU) regulated gel to foam toothpaste formulations versus a non-fluoride toothpaste using a modified in-situ model of dental erosion and remineralization. A positive control i.e fluoride containing toothpaste marketed in EU will also be compared to non-fluoride toothpaste.
Detailed description
The aim of this study is to assess the remineralization effects of two EU gel to foam toothpaste formulations with 1450 parts per million (ppm) of fluoride as sodium fluoride (NaF) and 5% potassium nitrate (KNO3) versus a non-fluoride (0 ppm F)/KNO3 toothpaste as a negative control. The two experimental gel to foam toothpaste formulations differ in their relative dentine abrasivity (RDA) values which is an in-vitro measure of a toothpaste abrasivity to the dentinal tissues. A marketed toothpaste containing NaF and KNO3 will serve as a positive control.
Interventions
DRUGSodium Fluoride
Toothpaste containing 1450 ppm F - EU level as NaF.
All study treatments contain 5% w/w KNO3.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* General and Oral Health: Good general health with (in the opinion of the investigator) no clinically OST and OHT examinations. * Oral Requirements: * An intact maxillary dental arch suitable for the retention of the palatal appliance and an intact mandibular dental arch. Subjects may have fixed bridges replacing missing teeth. * A gum base stimulated whole saliva flow rate ≥ 0.8 g/min and an unstimulated whole saliva flow rate ≥ 0.2 g/min. * Contraception: Women of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception.
Exclusion criteria
* Oral Health: * Current active caries or periodontal disease that may compromise the study or the health of the subjects. * Lesions of the oral cavity that could interfere with the study evaluations, including severe gingivitis, grossly carious lesions, periodontitis and other severe periodontal disease. * Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. * Clinical Study/Experimental Medication: * Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit * Previous participation in this study * Substance abuse: Recent history (within the last year) of alcohol or other substance abuse. * Pregnancy: Women who are pregnant or who are intending to become pregnant over the duration of the study * Breast-feeding: Women who are breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure | Baseline, 4 hours post treatment in each treatment period | Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: \[(E1-E2)/ (E1-B)\]\*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel. |
| Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure | Baseline, 4 hours post treatment in each treatment period | SMH test was used to assess mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMH 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 SMH recovery 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. A higher percentage values indicate a better outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| RER of Enamel Specimens Post 2 Hours of Treatment Exposure | Baseline, 2 hours post treatment in each treatment period | Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: \[(E1-E2)/ (E1-B)\]\*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel. |
| SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure | Baseline, 2 hours post treatment in each treatment period | SMH test was used to assess mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMH 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 SMH recovery 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. A higher percentage values indicate a better outcome. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants were evaluated for baseline parameters. | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 38.7 Years STANDARD_DEVIATION 13.77 |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 29 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 | 2 / 55 | 0 / 55 | 1 / 54 | 2 / 56 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 | 0 / 54 | 0 / 56 |
Outcome results
Primary
Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure
Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: \[(E1-E2)/ (E1-B)\]\*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel.
Time frame: Baseline, 4 hours post treatment in each treatment period
Population: Per protocol (PP) population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis. Due to drop outs, there was difference in number of participants analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NaF/KNO3 Toothpaste 1 | Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure | -36.66 Percentage RER | Standard Error 2.824 |
| NaF/KNO3 Toothpaste 2 | Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure | -36.53 Percentage RER | Standard Error 2.848 |
| NaF/KNO3 Toothpaste 3 | Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure | -36.98 Percentage RER | Standard Error 2.847 |
| No Fluoride/KNO3 Toothpaste | Relative Erosion Resistance (RER) of Enamel Specimens Post 4 Hours of Treatment Exposure | -77.82 Percentage RER | Standard Error 2.799 |
Comparison: Null hypothesis considered population means for the treatments in comparison to be equal with respect to %RER. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [34.42, 47.89]ANOVA
Comparison: Null hypothesis considered population means for the treatments in comparison to be equal with respect to %RER. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [34.51, 48.06]ANOVA
Comparison: Null hypothesis considered population means for the treatments in comparison to be equal with respect to %RER. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [34.06, 47.61]ANOVA
Primary
Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure
SMH test was used to assess mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMH 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 SMH recovery 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. A higher percentage values indicate a better outcome.
Time frame: Baseline, 4 hours post treatment in each treatment period
Population: PP population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis. Due to drop outs, there was difference in number of participants analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NaF/KNO3 Toothpaste 1 | Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure | 32.24 Percentage SMH | Standard Error 1.469 |
| NaF/KNO3 Toothpaste 2 | Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure | 32.32 Percentage SMH | Standard Error 1.48 |
| NaF/KNO3 Toothpaste 3 | Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure | 34.53 Percentage SMH | Standard Error 1.48 |
| No Fluoride/KNO3 Toothpaste | Surface Microhardness (SMH) Recovery of Enamel Specimens Post 4 Hours of Treatment Exposure | 22.87 Percentage SMH | Standard Error 1.457 |
Comparison: Null hypothesis considered population means for the treatments in comparison to be equal with respect to %SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [6.01, 12.72]ANOVA
Comparison: Null hypothesis considered population means for the treatments in comparison to be equal with respect to %SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [6.07, 12.82]ANOVA
Comparison: Null hypothesis considered population means for the treatments in comparison to be equal with respect to %SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [8.28, 15.03]ANOVA
Other Pre-specified
RER of Enamel Specimens Post 2 Hours of Treatment Exposure
Enamel specimens were exposed to dietary erosive challenge and set of five indentations within each specimen was measured. Decrease in the indentation length compared to the baseline indicates hardening of enamel surface. Enamel specimens were exposed to second erosion challenge to determine RER which compared the indentations values of enamel specimens at baseline (B), first erosive (E1) and second erosive challenge (E2). Percent RER was calculated by formula: \[(E1-E2)/ (E1-B)\]\*100. Smaller the negative RER, better is treatment regimen in imparting resistance to enamel.
Time frame: Baseline, 2 hours post treatment in each treatment period
Population: PP population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis. Due to drop outs, there was difference in number of participants analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NaF/KNO3 Toothpaste 1 | RER of Enamel Specimens Post 2 Hours of Treatment Exposure | -43.76 % RER | Standard Error 3.182 |
| NaF/KNO3 Toothpaste 2 | RER of Enamel Specimens Post 2 Hours of Treatment Exposure | -43.33 % RER | Standard Error 3.211 |
| NaF/KNO3 Toothpaste 3 | RER of Enamel Specimens Post 2 Hours of Treatment Exposure | -41.88 % RER | Standard Error 3.21 |
| No Fluoride/KNO3 Toothpaste | RER of Enamel Specimens Post 2 Hours of Treatment Exposure | -85.88 % RER | Standard Error 3.154 |
Other Pre-specified
SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure
SMH test was used to assess mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMH 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 SMH recovery 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. A higher percentage values indicate a better outcome.
Time frame: Baseline, 2 hours post treatment in each treatment period
Population: PP population: All randomized subjects who had at least one assessment of efficacy and considered unaffected by major protocol deviations, were included in analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NaF/KNO3 Toothpaste 1 | SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure | 28.96 Percentage SMH | Standard Error 1.6 |
| NaF/KNO3 Toothpaste 2 | SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure | 28.92 Percentage SMH | Standard Error 1.615 |
| NaF/KNO3 Toothpaste 3 | SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure | 28.30 Percentage SMH | Standard Error 1.615 |
| No Fluoride/KNO3 Toothpaste | SMH Recovery of Enamel Specimens Post 2 Hours of Treatment Exposure | 17.90 Percentage SMH | Standard Error 1.585 |