Dental Caries
Conditions
Keywords
Enamel remineralization, Fluoride, caries
Brief summary
This study will use an oral in-situ caries model to study remineralization of enamel due to the action of different combinations of fluoride salts delivered from dentifrices.
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Good general health with (in the opinion of the investigator) no clinically significant and relevant abnormalities of medical or oral health. * No current active caries or periodontal disease that may compromise the study or health of the subject. * All restorations in a good state of repair * Currently wearing a removable mandibular partial denture with sufficient room in the posterior buccal flange area to accomodate two enamel specimens required dimensions 12 x 7 mm. * Willing to have their denture modified to accomodate enamel test specimens * Willing and capable of wearing removable mandibular partial dentures 24 hours per day during the treatment periods. * Salivary flow rate in the range of normal values (unstimulated whole saliva flow rate greater than or equal to 0.2 mL/ minute; gum base stimulated whole saliva flow rate greater than or equal to 0.8 mL/minute.
Exclusion criteria
* Individuals currently taking antibiotics, or who have taken antibiotics within 30 days prior to the first treatment visit. * Current active caries or periodontal disease that may compromise the study or health of the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and SnF/NaF Toothpaste (1450ppmF) | Baseline to 14 days | SMH test was used to assess mineral status of partially demineralized enamel specimens using 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/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: \[(D-R)/(D-B)\]\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| %SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | Baseline to 14 days | SMH test was used to assess mineral status of partially demineralized enamel specimens using 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/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: \[(D-R)/ (D-B)\]\*100. |
| Change From Baseline in Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | Baseline to 14 days | Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Two to three days before the start of each treatment period, participants received a professional dental cleaning of their natural teeth, then brushed with the study wash out toothpaste and toothbrush.
Participants by arm
| Arm | Count |
|---|---|
| Overall All randomized participants | 83 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period I | Protocol Violation | 0 | 1 | 0 | 0 |
| Period I | Withdrawal by Subject | 0 | 0 | 1 | 1 |
| Period II | Protocol Violation | 0 | 1 | 0 | 0 |
| Period II | Withdrawal by Subject | 0 | 0 | 0 | 1 |
| Period III | Protocol Violation | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 64.0 Years STANDARD_DEVIATION 8.73 |
| Region of Enrollment United States | 83 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 35 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 | 10 / 79 | 12 / 79 | 18 / 80 | 15 / 80 |
| serious Total, serious adverse events | 0 / 79 | 0 / 79 | 1 / 80 | 0 / 80 |
Outcome results
Primary
Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and SnF/NaF Toothpaste (1450ppmF)
SMH test was used to assess mineral status of partially demineralized enamel specimens using 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/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: \[(D-R)/(D-B)\]\*100.
Time frame: Baseline to 14 days
Population: Per Protocol (PP) population: All randomized participants, who received at least one dose of study treatment and with at least one post-baseline efficacy assessment but did not have any major protocol violations. Missing data was not imputed. Due to drop outs, there were differences in number of participants (N) per treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1450ppmF) | Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and SnF/NaF Toothpaste (1450ppmF) | 40.94 Percentage of SMHR | Standard Error 1.93 |
| SnF/NaF Toothpaste (1450ppmF) | Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF) and SnF/NaF Toothpaste (1450ppmF) | 17.88 Percentage of SMHR | Standard Error 1.924 |
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [19.63, 26.48]ANOVA
Secondary
Change From Baseline in Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF)
Enamel fluoride uptake was determined using the microdrill enamel biopsy technique. The amount of fluoride uptake by enamel was calculated based on the amount of fluoride (F) divided by the area of the enamel cores. The difference between treatments was calculated with respect to fluoride uptake by enamel.
Time frame: Baseline to 14 days
Population: PP population: All randomized participants, who received at least one dose of study treatment and with at least one post-baseline efficacy assessment but did not have any major protocol violations. Missing data was not imputed. Due to drop outs, there were differences in number of participants (N) per treatment group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1450ppmF) | Change From Baseline in Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 22.23 micrograms (μg)*F/centimeters(cm)^2] | Standard Error 0.853 |
| SnF/NaF Toothpaste (1450ppmF) | Change From Baseline in Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 13.54 micrograms (μg)*F/centimeters(cm)^2] | Standard Error 0.854 |
| SnF/NaF Toothpaste (1450ppmF) | Change From Baseline in Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 9.13 micrograms (μg)*F/centimeters(cm)^2] | Standard Error 0.85 |
| NaF Toothpaste (675ppmF) | Change From Baseline in Enamel Fluoride Uptake Upon Exposure to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 14.31 micrograms (μg)*F/centimeters(cm)^2] | Standard Error 0.861 |
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [11.46, 14.96]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [7.04, 10.55]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [6.25, 9.8]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [2.66, 6.16]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.p-value: 0.394295% CI: [-2.54, 1]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to enamel fluoride uptake. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [-6.95, -3.41]ANOVA
Secondary
%SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF)
SMH test was used to assess mineral status of partially demineralized enamel specimens using 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/demineralization, while decrease in the indentation represents rehardening/ remineralization of enamel surface. Percent SMH recovery was calculated from indentation values of enamel specimens at baseline(B), after intra-oral exposure(R) and after in-vitro demineralization(D) using formula: \[(D-R)/ (D-B)\]\*100.
Time frame: Baseline to 14 days
Population: PP population: All randomized participants, who received at least one dose of study treatment and with at least one post-baseline efficacy assessment but did not have any major protocol violations. Missing data was not imputed. Due to drop outs, there were differences in number of participants (N) per treatment group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1450ppmF) | %SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 40.94 Percentage | Standard Error 1.93 |
| SnF/NaF Toothpaste (1450ppmF) | %SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 30.19 Percentage | Standard Error 1.932 |
| SnF/NaF Toothpaste (1450ppmF) | %SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 17.88 Percentage | Standard Error 1.924 |
| NaF Toothpaste (675ppmF) | %SMHR of Enamel Specimens Exposed to NaF Toothpaste (1450ppmF), SnF/NaF Toothpaste (1450ppmF), NaMFP/NaF Toothpaste (1450ppmF) and NaF Toothpaste (675ppmF) | 28.74 Percentage | Standard Error 1.943 |
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [7.33, 14.17]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [8.74, 15.67]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [8.9, 15.72]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: 0.40795% CI: [-2, 4.91]ANOVA
Comparison: Null hypothesis considered population means for treatments in comparison, to be equal with respect to percent SMH recovery. Statistical tests were 2-sided with a significance level of 0.05.p-value: <0.000195% CI: [-14.3, -7.4]ANOVA