Dental Erosion
Conditions
Keywords
enamel fluoride uptake, erosion, enamel remineralization
Brief summary
The purpose of this study is to determine whether an experimental fluoridated dentifrice is effective in the treatment of dental caries
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. Determination of fluoride uptake in-situ also provides better estimation of true fluoride bioavailability of fluoride dentifrice products. In this study, an in-situ remineralization fluoride uptake model will be used to compare the efficacy of experimental dentifrice with a marketed dentifrice and placebo dentifrice. Participants wore partial dentures containing two partially demineralized enamel specimens for two weeks- 24 hours per day, except when brushing (twice daily) with test dentifrice. Following each treatment period, the enamel specimens were analyzed for SMH recovery and fluoride uptake through microdrill enamel biopsy technique.
Interventions
DRUGNaF/ KNO3/isopentane Dentifrice
Experimental toothpaste
DRUGNaF/KNO3 Dentifrice
Experimental toothpaste
DRUGNaF Dentifrice
Active comparator
OTHERPlacebo Dentifrice
Placebo comparator
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age: Aged between 18 and 78 2. Fluoride: Currently living in the Indianapolis area which has a fluoridated water supply (1 ppm F) and not taking fluoride supplements for medical reasons 3. Dentures: 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 mm). Willing and capable of wearing their removable partial dentures 24 hours per day during the experimental periods 4. Dental health:Have no current active caries or periodontal disease that may compromise the study or the health of the participants and all restorations in a good state of repair 5. Salivary flow:Have a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate ≥ 0.2 mL/min; gum base stimulated whole saliva flow rate ≥ 0.8 mL/min 6. Compliance: Understands and is willing, able and likely to comply with all study procedures and restrictions 7. 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 8. 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 participant safety during the study period
Exclusion criteria
1. Antibiotics:Currently taking antibiotics or have taken antibiotics in the two weeks prior to the screening visit 2. Allergy/Intolerance:Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients 3. Pregnancy:Women who are known to be pregnant or who are intending to become pregnant over the duration of the study. 4. Breast-feeding:Women who are breast-feeding. 5. Clinical Study/Experimental Medication: Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit 6. Personnel:An employee of the sponsor or the study site who is directly involved in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens | Baseline to 14 days | 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 re-hardening of enamel surface. Percent 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 |
|---|---|---|
| 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/cm\^3. 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 to three days before the start of each treatment period participants got their teeth cleaned to remove all accessible plaque and calculus, and were provided with a fluoride free dentifrice for maintaining wash-out period and standardizing the oral conditions.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Participants All randomized participants who received all four treatments NaF/ KNO3/ 2% isopentane Dentifrice, NaF/KNO3/ 0% isopentane Dentifrice, NaF Dentifrice, and placebo were included in the baseline assessment. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Cannot continue the study | 1 |
| Overall Study | Could not attend visit 9 | 1 |
| Overall Study | Not capable of wearing partial denture | 1 |
| Overall Study | Protocol Deviation | 2 |
Baseline characteristics
| Characteristic | Overall Study Participants |
|---|---|
| Age, Continuous | 65.31 years STANDARD_DEVIATION 8.226 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 7 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 / 17 | 3 / 17 | 4 / 18 | 2 / 18 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 18 | 0 / 18 |
Outcome results
Primary
Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens
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 re-hardening of enamel surface. Percent 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: Per-Protocol (PP) population: All randomized participants who received at least one dose of study product, had at least one post-baseline efficacy assessments and no major protocol deviations. 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/ KNO3/ 2% Isopentane Dentifrice | Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens | 39.46 % SMHR | 95% Confidence Interval 4.1 |
| NaF/KNO3/ 0% Isopentane Dentifrice | Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens | 38.31 % SMHR | 95% Confidence Interval 4.11 |
| NaF Dentifrice | Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens | 36.17 % SMHR | 95% Confidence Interval 4.1 |
| Placebo Dentifrice | Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens | 17.26 % SMHR | 95% Confidence Interval 4.04 |
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: 0.775695% CI: [-6.904, 9.196]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: 0.419495% CI: [-4.84, 11.421]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: <0.000195% CI: [14.28, 30.12]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: 0.592795% CI: [-5.874, 10.164]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: <0.000195% CI: [13.189, 28.919]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: <0.000195% CI: [11.036, 26.783]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/cm\^3. 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 product, had at least one post-baseline efficacy assessments and no major protocol deviations. 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/ KNO3/ 2% Isopentane Dentifrice | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 2445.86 ug*F/cm^3 | 95% Confidence Interval 256.55 |
| NaF/KNO3/ 0% Isopentane Dentifrice | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 2767.30 ug*F/cm^3 | 95% Confidence Interval 257.16 |
| NaF Dentifrice | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 2518.54 ug*F/cm^3 | 95% Confidence Interval 256.55 |
| Placebo Dentifrice | Adjusted Mean Change From Baseline in Enamel Fluoride Uptake | 661.18 ug*F/cm^3 | 95% Confidence Interval 252.88 |
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: 0.19995% CI: [-818.118, 175.242]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: 0.771895% CI: [-574.398, 429.039]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: <0.000195% CI: [1296.044, 2273.306]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: 0.316495% CI: [-245.962, 743.478]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: <0.000195% CI: [1620.906, 2591.32]ANOVA
Comparison: Null hypothesis was no difference between treatments. Tests were 2-sided.p-value: <0.000195% CI: [1371.637, 2343.072]ANOVA