Healthy Subjects, Partial Denture Wearers, Caries
Conditions
Keywords
remineralization, enamel, fluoride, caries, in situ
Brief summary
This study is to evaluate the effect of fluoride dentifrices on enamel with artificial caries lesions in an in situ model.
Detailed description
Topical fluorides have been proven to be clinically effective in the prevention of dental caries. It is generally agreed that anti-caries effect of fluoride (F) is mainly by decreasing the rate of enamel demineralization and enhancing the rate of enamel remineralization. An in-situ Surface Micro-hardness (SMH) test is widely used to evaluate enamel demineralization and remineralization during the caries process. The aim of this study was to evaluate the efficacy of toothpaste formulations containing fluoride from different sources \[sodium fluoride (NaF) and sodium monofluorophosphate (NaMFP)\] using an in situ caries model.
Interventions
Various fluoride toothpastes containing 1350 ppm F, 1450 ppm F, 1400 ppm F and 250 ppm F
Fluoride free toothpaste (0 ppm F)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
Yes
Inclusion criteria
1. Consent: Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form. 2. Age:Aged between 18 and 78 years. 3. Compliance:Understands and is willing, able and likely to comply with all study procedures and restrictions. 4. General Health:Good general health with (in the opinion of the investigator) no clinically significant and/or relevant abnormalities of medical history or oral examination that could interfere with subject safety during the study period. 5. Diagnosis: Oral - i. Currently living in the Indianapolis area which is a fluoridated community (1 ppm F). ii. Currently wearing a removable mandibular partial denture with sufficient room in the posterior buccal flange area to accommodate two enamel specimens (required dimensions 12 x 7 millimeters (mm). iii. Willing and capable of wearing their removable partial dentures 24 hours per day during each two week treatment period. iv.All restorations in a good state of repair. 6. Salivary Flow:Have a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate = 0.2 ml/minute; gum base stimulated whole saliva flow rate = 0.8 ml/minute).
Exclusion criteria
1. Pregnancy:Women who are known to be pregnant or who are intending to become pregnant over the duration of the study. No pregnancy test will be required. 2. Breast-feeding:Women who are breast-feeding. 3. Allergy/Intolerance: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. 4. Clinical Study/Experimental Medication:Participation in another clinical study or receipt of an investigational drug within 30 days of the first treatment visit, with the exception of study T3157495 where the wash in period prior to treatment is sufficient. 5. Antibiotics:Currently taking antibiotics or have taken antibiotics in the 2 weeks prior to the screening visit. 6. Fluoride:Taking fluoride supplements for medical reasons. 7. Dental Health: Current active caries or periodontal disease that may compromise the study or health of the subjects. 8. Personnel: a) A member of the site study staff, b) An employee of the sponsor, c) Any employee of any toothpaste manufacturer or their spouse or family member.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF) Compared to NaMFP/NaF Toothpaste (1450ppmF) | Baseline to 14 days | %SMHR test was used to assess 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. %SMHR 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 |
|---|---|---|
| Mean %SMHR of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (250ppmF) and Placebo Toothpaste (0ppmF) | Baseline to 14 days | %SMHR test was used to assess 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. %SMHR 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. |
| Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 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 and expressed as ug F/cm2. The difference between treatments was calculated with respect to fluoride uptake by enamel. |
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
Two days, prior to each treatment visit ,participants used a fluoride- free dentifrice twice daily to avoid any carry over effect.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All randomized participants were included for baseline evaluation. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Period 1 | Protocol Violation | 0 | 1 | 0 | 1 | 0 |
| Period 2 | Other Reason | 1 | 0 | 0 | 0 | 0 |
| Period 2 | Protocol Violation | 0 | 0 | 0 | 1 | 0 |
| Period 3 | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 |
| Period 4 | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age Continuous | 67.31 years STANDARD_DEVIATION 9.166 |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 33 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 | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 56 | 4 / 54 | 1 / 55 | 1 / 56 | 2 / 54 |
| serious Total, serious adverse events | 0 / 56 | 0 / 54 | 0 / 55 | 0 / 56 | 0 / 54 |
Outcome results
Primary
Mean Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF) Compared to NaMFP/NaF Toothpaste (1450ppmF)
%SMHR test was used to assess 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. %SMHR 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: Intent to treat population: All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to subject drop outs, there are differences in the n per treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NaF/Carbopol Toothpaste (1400 Ppm F) | Mean Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF) Compared to NaMFP/NaF Toothpaste (1450ppmF) | 33.54 %SMHR | Standard Error 1.72 |
| NaF Toothpaste (1350 Ppm F) | Mean Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF) Compared to NaMFP/NaF Toothpaste (1450ppmF) | 35.23 %SMHR | Standard Error 1.74 |
| NaMFP/NaF Toothpaste (1450 Ppm F) | Mean Percentage Surface Microhardness Recovery (%SMHR) of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF) Compared to NaMFP/NaF Toothpaste (1450ppmF) | 29.57 %SMHR | Standard Error 1.72 |
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.026595% CI: [0.47, 7.48]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.001795% CI: [2.15, 9.18]ANOVA
Secondary
Adjusted Mean Change From Baseline in 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 the amount of fluoride (F) divided by the area of the enamel cores and expressed as ug F/cm2. The difference between treatments was calculated with respect to fluoride uptake by enamel.
Time frame: Baseline to 14 days
Population: ITT population: All randomized participants who had a least one post baseline efficacy assessment. Missing data was not imputed. Due to drop outs, there were differences in the n per treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NaF/Carbopol Toothpaste (1400 Ppm F) | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 1283.13 µg*F/cm^2 | Standard Error 71.53 |
| NaF Toothpaste (1350 Ppm F) | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 1333.09 µg*F/cm^2 | Standard Error 72.08 |
| NaMFP/NaF Toothpaste (1450 Ppm F) | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 680.20 µg*F/cm^2 | Standard Error 71.48 |
| NaMFP/NaF Toothpaste (1450 Ppm F) | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 1086.39 µg*F/cm^2 | Standard Error 71.42 |
| Placebo Toothpaste (0 Ppm F) | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 435.58 µg*F/cm^2 | Standard Error 71.54 |
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.002495% CI: [87.62, 401.61]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided at 5% significance level.p-value: 0.014895% CI: [38.89, 354.6]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.002495% CI: [88.3, 405.1]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.532895% CI: [-207.62, 107.71]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [-564, -248.37]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [445.97, 759.9]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [495.05, 810.72]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [690.54, 1004.55]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [739.92, 1055.08]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [493.61, 808]ANOVA
Secondary
Mean %SMHR of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (250ppmF) and Placebo Toothpaste (0ppmF)
%SMHR test was used to assess 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. %SMHR 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: ITT population: All randomized participants who had at least one post baseline efficacy assessment. Missing data was not imputed. Due to drop outs, there were differences in the n per treatment group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NaF/Carbopol Toothpaste (1400 Ppm F) | Mean %SMHR of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (250ppmF) and Placebo Toothpaste (0ppmF) | 33.54 %SMHR | Standard Error 1.72 |
| NaF Toothpaste (1350 Ppm F) | Mean %SMHR of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (250ppmF) and Placebo Toothpaste (0ppmF) | 35.23 %SMHR | Standard Error 1.74 |
| NaMFP/NaF Toothpaste (1450 Ppm F) | Mean %SMHR of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (250ppmF) and Placebo Toothpaste (0ppmF) | 24.98 %SMHR | Standard Error 1.72 |
| NaMFP/NaF Toothpaste (1450 Ppm F) | Mean %SMHR of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (250ppmF) and Placebo Toothpaste (0ppmF) | 29.57 %SMHR | Standard Error 1.72 |
| Placebo Toothpaste (0 Ppm F) | Mean %SMHR of Enamel Specimens Exposed to NaF/Carbopol Toothpaste (1400 ppmF), NaF Toothpaste (1350ppmF), NaMFP/NaF Toothpaste (1450ppmF), NaF Toothpaste (250ppmF) and Placebo Toothpaste (0ppmF) | 22.05 %SMHR | Standard Error 1.73 |
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.341395% CI: [-5.19, 1.8]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [6.76, 13.76]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [9.69, 16.68]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [5.09, 12.05]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [8.01, 14.98]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.010495% CI: [-8.1, -1.09]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: <0.000195% CI: [4.04, 11.01]ANOVA
Comparison: Null hypothesis was no difference between treatments being compared. Tests were 2-sided at 5% significance level.p-value: 0.098695% CI: [-0.55, 6.41]ANOVA