Oral Hygiene
Conditions
Brief summary
This study will evaluate the effect of experimental sodium fluoride-silica dentifrice formulations, with and without zinc, on remineralization of enamel in situ. Following the remineralization phase, the acid resistance of the new mineral formed will be assessed. Fluoride uptake during the remineralization phase will also be measured.
Interventions
DRUGSodium fluoride (1426 ppm)
Non-zinc, 1426ppm fluoride as sodium fluoride in a silica gel base
DRUGSodium fluoride (1150 ppm)
Non-zinc, 1150ppm fluoride as sodium fluoride in a silica gel base
DRUGSodium fluoride (250 ppm)
Non-zinc, 250ppm fluoride as sodium fluoride in a silica gel base
DRUGSodium fluoride (1426 ppm) + zinc base A
Zinc base A, 1426ppm fluoride as sodium fluoride in a silica gel base
DRUGSodium fluoride (1426 ppm) + zinc base B
Zinc base B, 1426ppm fluoride as sodium fluoride in a silica gel base
DRUGFluoride (0 ppm)
Non-zinc, 0ppm fluoride in a silica gel base
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Good general health with no clinically significant and relevant abnormalities of medical history or oral examination * Participants with maxillary dental arch suitable for the retention of the palatal appliance
Exclusion criteria
* Participants taking fluoride supplement * Pregnant or breast-feeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Surface Microhardness Recovery (% SMHR) | Baseline to 4 hours | Changes in the mineral content of the four centrally-located enamel specimens were evaluated using the Surface Microhardness (SMH) Test. The SMH was measured using a Wilson 2100 Hardness Tester. The baseline SMH was determined prior to the in vitro acid challenge. SMH was determined again after the in vitro acid challenge, after the in situ remineralization test, and again after the second in vitro acid challenge. The extent of remineralization was calculated as the % recovery in SMH using the equation: % SMHR= \[(D1-R)/(D1-B)\]\*100 Where B = indentation length (μm) of sound enamel at baseline; D1 = indentation length (μm) after first acid challenge; R = indentation length (μm) after in situ remineralization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Enamel Fluoride Uptake | Baseline to 4 hours | The microdrill enamel biopsy technique was used to analyze the fluoride uptake by enamel. Each enamel specimen was mounted on the long axis of a drill attached to a microdrill and drilled to a depth of approximately 100 micrometer (μm) through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling sample was then immediately analyzed for fluoride content using fluoride specific electrode and pH/ion meter. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram per square centimeter (μg/cm\^2). |
| Percentage Net Acid Resistance (% NAR) | Baseline to 4 hours | Changes in the mineral content of the four centrally-located enamel specimens were evaluated using the SMH Test. The SMH was measured using a Wilson 2100 Hardness Tester. The baseline SMH was measured prior to the in vitro acid challenge. SMH was measured again after the in vitro acid challenge, after the in situ remineralization test, and again after the second in vitro acid challenge. The % NAR was calculated using the equation: % NAR= \[(D1-D2)/(D1-B)\]\*100 where B= Indentation length (μm) of sound enamel at baseline; D1= Indentation length (μm) after first acid challenge and D2= Indentation length (μm) after second acid challenge. |
| Percentage Comparative Acid Resistance (% CAR) | Baseline to 4 hours | Changes in the mineral content of the four centrally-located enamel specimens were evaluated using the SMH Test. The SMH was measured using a Wilson 2100 Hardness Tester. The baseline SMH was measured prior to the in vitro acid challenge. SMH was measured again after the in vitro acid challenge, after the in situ remineralization test, and again after the second in vitro acid challenge. The % CAR was calculated using the equation: % CAR= \[(D2-R)/(D1-B)\]\*100 where B= Indentation length (μm) of sound enamel at baseline; R= Indentation length (μm) of enamel after in situ remineralization; D1= Indentation length (μm) after first acid challenge; D2= Indentation length (μm) after second acid challenge. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at one clinical study site in the USA.
Pre-assignment details
A total of 64 participants were screened and 62 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants were evaluated for baseline characteristics | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other Reason | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 40.7 Years STANDARD_DEVIATION 12.03 |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 23 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 59 | 1 / 57 | 5 / 55 | 1 / 58 | 4 / 60 | 5 / 59 |
| serious Total, serious adverse events | 0 / 59 | 0 / 57 | 0 / 55 | 0 / 58 | 1 / 60 | 0 / 59 |
Outcome results
Primary
Percentage Surface Microhardness Recovery (% SMHR)
Changes in the mineral content of the four centrally-located enamel specimens were evaluated using the Surface Microhardness (SMH) Test. The SMH was measured using a Wilson 2100 Hardness Tester. The baseline SMH was determined prior to the in vitro acid challenge. SMH was determined again after the in vitro acid challenge, after the in situ remineralization test, and again after the second in vitro acid challenge. The extent of remineralization was calculated as the % recovery in SMH using the equation: % SMHR= \[(D1-R)/(D1-B)\]\*100 Where B = indentation length (μm) of sound enamel at baseline; D1 = indentation length (μm) after first acid challenge; R = indentation length (μm) after in situ remineralization.
Time frame: Baseline to 4 hours
Population: The primary population for the efficacy analysis was the Per Protocol (PP) population, including participants with a protocol violation affecting some (but not all) of the efficacy assessments. However, data from assessments when a violation occurred were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sodium Fluoride (1426 Ppm) | Percentage Surface Microhardness Recovery (% SMHR) | 32.49 Percentage of SMHR | Standard Error 1.167 |
| Sodium Fluoride (1150 Ppm) | Percentage Surface Microhardness Recovery (% SMHR) | 31.81 Percentage of SMHR | Standard Error 1.182 |
| Sodium Fluoride (250 Ppm) | Percentage Surface Microhardness Recovery (% SMHR) | 27.56 Percentage of SMHR | Standard Error 1.199 |
| Sodium Fluoride (1426 Ppm) + Zinc Base A | Percentage Surface Microhardness Recovery (% SMHR) | 22.62 Percentage of SMHR | Standard Error 1.175 |
| Sodium Fluoride (1426 Ppm) + Zinc Base B | Percentage Surface Microhardness Recovery (% SMHR) | 23.22 Percentage of SMHR | Standard Error 1.159 |
| Sodium Fluoride (0 Ppm) | Percentage Surface Microhardness Recovery (% SMHR) | 24.78 Percentage of SMHR | Standard Error 1.167 |
Comparison: Linear contrasts were fitted in order to establish whether there was a dose-response relationship. Linear contrasts were for experimental dentifrice: non-zinc treatments.p-value: <0.0001ANOVA
Comparison: Quadratic contrasts were fitted in order to establish whether there was a dose-response relationship. Quadratic contrasts are for experimental dentifrice: non-zinc treatments.p-value: 0.2274ANOVA
p-value: 0.59595% CI: [-1.84, 3.2]ANOVA
p-value: 0.000295% CI: [2.38, 7.48]ANOVA
p-value: 0.001395% CI: [1.68, 6.82]ANOVA
p-value: <0.000195% CI: [5.2, 10.21]ANOVA
p-value: <0.000195% CI: [4.51, 9.55]ANOVA
p-value: 0.032595% CI: [0.23, 5.32]ANOVA
p-value: 0.09295% CI: [-4.67, 0.35]ANOVA
p-value: 0.218595% CI: [-4.04, 0.93]ANOVA
p-value: <0.000195% CI: [7.36, 12.37]ANOVA
p-value: <0.000195% CI: [6.77, 11.75]ANOVA
Secondary
Enamel Fluoride Uptake
The microdrill enamel biopsy technique was used to analyze the fluoride uptake by enamel. Each enamel specimen was mounted on the long axis of a drill attached to a microdrill and drilled to a depth of approximately 100 micrometer (μm) through the entire lesion (four cores per specimen). The enamel powder pooled from four drilling sample was then immediately analyzed for fluoride content using fluoride specific electrode and pH/ion meter. The amount of fluoride-uptake by enamel was calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as microgram per square centimeter (μg/cm\^2).
Time frame: Baseline to 4 hours
Population: The main population for the secondary efficacy analysis was the PP population, including participants with a protocol violation affecting some (but not all) of the efficacy assessments. However, data from assessments when a violation occurred were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sodium Fluoride (1426 Ppm) | Enamel Fluoride Uptake | 2.94 microgram per square centimeter(μg/cm^2) | Standard Error 0.083 |
| Sodium Fluoride (1150 Ppm) | Enamel Fluoride Uptake | 2.70 microgram per square centimeter(μg/cm^2) | Standard Error 0.084 |
| Sodium Fluoride (250 Ppm) | Enamel Fluoride Uptake | 1.85 microgram per square centimeter(μg/cm^2) | Standard Error 0.085 |
| Sodium Fluoride (1426 Ppm) + Zinc Base A | Enamel Fluoride Uptake | 2.62 microgram per square centimeter(μg/cm^2) | Standard Error 0.083 |
| Sodium Fluoride (1426 Ppm) + Zinc Base B | Enamel Fluoride Uptake | 2.37 microgram per square centimeter(μg/cm^2) | Standard Error 0.082 |
| Sodium Fluoride (0 Ppm) | Enamel Fluoride Uptake | 0.98 microgram per square centimeter(μg/cm^2) | Standard Error 0.083 |
Secondary
Percentage Comparative Acid Resistance (% CAR)
Changes in the mineral content of the four centrally-located enamel specimens were evaluated using the SMH Test. The SMH was measured using a Wilson 2100 Hardness Tester. The baseline SMH was measured prior to the in vitro acid challenge. SMH was measured again after the in vitro acid challenge, after the in situ remineralization test, and again after the second in vitro acid challenge. The % CAR was calculated using the equation: % CAR= \[(D2-R)/(D1-B)\]\*100 where B= Indentation length (μm) of sound enamel at baseline; R= Indentation length (μm) of enamel after in situ remineralization; D1= Indentation length (μm) after first acid challenge; D2= Indentation length (μm) after second acid challenge.
Time frame: Baseline to 4 hours
Population: The main population for the secondary efficacy analysis was the PP population, including participants with a protocol violation affecting some (but not all) of the efficacy assessments. However, data from assessments when a violation occurred were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sodium Fluoride (1426 Ppm) | Percentage Comparative Acid Resistance (% CAR) | 45.00 Percentage of CAR | Standard Error 1.274 |
| Sodium Fluoride (1150 Ppm) | Percentage Comparative Acid Resistance (% CAR) | 45.23 Percentage of CAR | Standard Error 1.295 |
| Sodium Fluoride (250 Ppm) | Percentage Comparative Acid Resistance (% CAR) | 45.44 Percentage of CAR | Standard Error 1.319 |
| Sodium Fluoride (1426 Ppm) + Zinc Base A | Percentage Comparative Acid Resistance (% CAR) | 40.29 Percentage of CAR | Standard Error 1.285 |
| Sodium Fluoride (1426 Ppm) + Zinc Base B | Percentage Comparative Acid Resistance (% CAR) | 42.21 Percentage of CAR | Standard Error 1.264 |
| Sodium Fluoride (0 Ppm) | Percentage Comparative Acid Resistance (% CAR) | 75.41 Percentage of CAR | Standard Error 1.274 |
Secondary
Percentage Net Acid Resistance (% NAR)
Changes in the mineral content of the four centrally-located enamel specimens were evaluated using the SMH Test. The SMH was measured using a Wilson 2100 Hardness Tester. The baseline SMH was measured prior to the in vitro acid challenge. SMH was measured again after the in vitro acid challenge, after the in situ remineralization test, and again after the second in vitro acid challenge. The % NAR was calculated using the equation: % NAR= \[(D1-D2)/(D1-B)\]\*100 where B= Indentation length (μm) of sound enamel at baseline; D1= Indentation length (μm) after first acid challenge and D2= Indentation length (μm) after second acid challenge.
Time frame: Baseline to 4 hours
Population: The main population for the secondary efficacy analysis was the PP population, including participants with a protocol violation affecting some (but not all) of the efficacy assessments. However, data from assessments when a violation occurred were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sodium Fluoride (1426 Ppm) | Percentage Net Acid Resistance (% NAR) | -12.54 Percentage of NAR | Standard Error 1.224 |
| Sodium Fluoride (1150 Ppm) | Percentage Net Acid Resistance (% NAR) | -13.45 Percentage of NAR | Standard Error 1.244 |
| Sodium Fluoride (250 Ppm) | Percentage Net Acid Resistance (% NAR) | -17.81 Percentage of NAR | Standard Error 1.266 |
| Sodium Fluoride (1426 Ppm) + Zinc Base A | Percentage Net Acid Resistance (% NAR) | -17.60 Percentage of NAR | Standard Error 1.234 |
| Sodium Fluoride (1426 Ppm) + Zinc Base B | Percentage Net Acid Resistance (% NAR) | -18.98 Percentage of NAR | Standard Error 1.214 |
| Sodium Fluoride (0 Ppm) | Percentage Net Acid Resistance (% NAR) | -50.60 Percentage of NAR | Standard Error 1.224 |