Caries
Conditions
Keywords
remineralization, enamel, in situ, fluoride, caries
Brief summary
This study is to evaluate the effect of fluoride dentrifrices on enamel with artificial caries lesions in an in situ model
Interventions
Test product
DRUGAmine Fluoride Toothpaste
Test product
DRUGSodium monofluorophosphate/Sodium Fluoride Toothpaste
test product
DRUGPlacebo
placebo and washout treatment
DRUG675 ppmf toothpaste
dose response
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* 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 * Age:Aged 18 to 80 years inclusive * Compliance: Understands and is willing, able and likely to comply with all study procedures and restrictions * 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 * Residency: Currently living in the Indianapolis, Indiana area * Dentures: a) 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). b) Willing and capable of wearing their removable partial dentures 24 hours per day during each two week treatment period. c) All restorations in a good state of repair * 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
* Pregnancy:Women who are known to be pregnant or who are intending to become pregnant over the duration of the study * Breast-feeding: Women who are breast-feeding * 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: a. Participation in another clinical study or receipt of an investigational drug within 30 days of the first treatment visit, with the exception of study GSK dental studies where the wash in period prior to treatment is sufficient. b. Previous participation in this study * Antibiotics: Currently taking antibiotics or have taken antibiotics in the two weeks prior to the screening visit * Fluoride: Prescribed or professionally recommended use of fluoride supplements or fluoride mouthrinse * Substance abuse: Recent history (within last year) of alcohol or other substance abuse * Dental Health: Current active caries or periodontal disease that may compromise the study or health of the subjects * Personnel: a. A member of the site study staff who is directly working on the project or living in that staff's household. 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 |
|---|---|---|
| Percent Surface Microhardness (SMH) Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF) and AmF Toothpaste (1400ppmF) | Baseline to 14 days | SMH recovery test was used to assess the changes in 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. Difference in percent SMH recovery was calculated by comparing study NaF toothpaste (1426ppmF) with reference AmF toothpaste (1400ppmF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent SMH Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste (1400ppm F) and Placebo (0ppmF) | Baseline to 14 days | SMH test was used to assess the changes in 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. Differences in percent SMH recovery due to study and reference toothpastes were calculated. |
| Change From Baseline in Enamel Fluoride Uptake Potential | 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. |
Participant flow
Recruitment details
Participants were recruited at the clinical site.
Pre-assignment details
83 participants were screened and 18 participants did not meet the study criteria thus 65 participants were enrolled into the study. The subjects were randomized to receive all 5 study treatments in a pre-determined computerized randomised order as per a typical cross-over design.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants who received at least one dose of the study treatments or who have been evaluated for AEs were included. | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Treatment Period 1 (14 Days) | Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Treatment Period 1 (14 Days) | Protocol Violation | 1 | 0 | 1 | 0 | 0 |
| Treatment Period 2 (14 Days) | Adverse Event | 0 | 1 | 1 | 0 | 0 |
| Treatment Period 2 (14 Days) | Protocol Violation | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 2 (14 Days) | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
| Treatment Period 3 (14 Days) | Protocol Violation | 0 | 1 | 0 | 0 | 1 |
| Treatment Period 4 (14 Days) | Other Reason | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 4 (14 Days) | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Washout Period 1 (4 Days) | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age Continuous | 67.0 years STANDARD_DEVIATION 9.97 |
| Region of Enrollment United States | 65 participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 24 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 | 1 / 57 | 5 / 57 | 0 / 59 | 3 / 59 | 2 / 59 | 10 / 65 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 | 0 / 59 | 0 / 59 | 0 / 59 | 0 / 65 |
Outcome results
Primary
Percent Surface Microhardness (SMH) Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF) and AmF Toothpaste (1400ppmF)
SMH recovery test was used to assess the changes in 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. Difference in percent SMH recovery was calculated by comparing study NaF toothpaste (1426ppmF) with reference AmF toothpaste (1400ppmF).
Time frame: Baseline to 14 days
Population: Per protocol (PP) population: All randomized participants who received at least one dose of the study treatments and provided at least one measurement SMH. Participants without any major protocol violations in given study treatment period were included in the PP population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1426ppmF) | Percent Surface Microhardness (SMH) Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF) and AmF Toothpaste (1400ppmF) | 38.05 Percentage SMHR | Standard Error 2.52 |
| AmF Toothpaste (1400ppmF) | Percent Surface Microhardness (SMH) Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF) and AmF Toothpaste (1400ppmF) | 41.06 Percentage SMHR | Standard Error 2.53 |
Comparison: Null hypothesis considered population means for NaF toothpaste and AmF toothpaste to be equal with respect to enamel remineralization potential.p-value: 0.211795% CI: [-7.75, 1.73]ANOVA
Secondary
Change From Baseline in Enamel Fluoride Uptake Potential
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 the study treatments or provided at least one significant measurement of fluoride uptake. Participants without any major protocol violations in given study treatment period were included in the PP population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1426ppmF) | Change From Baseline in Enamel Fluoride Uptake Potential | 2342.35 micrograms (μg)* F/centimeters(cm)^2 | Standard Error 123.65 |
| AmF Toothpaste (1400ppmF) | Change From Baseline in Enamel Fluoride Uptake Potential | 2305.11 micrograms (μg)* F/centimeters(cm)^2 | Standard Error 123.83 |
| NaMFP/NaF Toothpaste (1450ppmF) | Change From Baseline in Enamel Fluoride Uptake Potential | 1809.74 micrograms (μg)* F/centimeters(cm)^2 | Standard Error 121.83 |
| NaF Toothpaste (675ppmF) | Change From Baseline in Enamel Fluoride Uptake Potential | 1649.44 micrograms (μg)* F/centimeters(cm)^2 | Standard Error 121.93 |
| Placebo Toothpaste (0ppmF) | Change From Baseline in Enamel Fluoride Uptake Potential | 462.95 micrograms (μg)* F/centimeters(cm)^2 | Standard Error 120.92 |
Comparison: Null hypothesis considered population means for the NaF toothpaste (1426ppmF) and AmF toothpaste (1400ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: 0.791295% CI: [-239.62, 314.09]ANOVA
Comparison: Null hypothesis considered population means for the NaF toothpaste (1426ppmF) and Na MFP/NaF toothpaste (1450ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: 0.000295% CI: [259.06, 806.16]ANOVA
Comparison: Null hypothesis considered population means for the NaF toothpaste (1426ppmF) and NaF toothpaste (675ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: <0.000195% CI: [418.73, 967.09]ANOVA
Comparison: Null hypothesis considered population means for the NaF toothpaste (1426ppmF) and Placebo toothpaste (0ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: <0.000195% CI: [1605.75, 2153.04]ANOVA
Comparison: Null hypothesis considered population means for AmF toothpaste (1400ppmF) and Na MFP/ NaF toothpaste (1450ppmF) and to be equal with respect to enamel fluoride uptake potential.p-value: 0.000595% CI: [221.09, 769.66]ANOVA
Comparison: Null hypothesis considered population means for AmF toothpaste (1400ppmF) and NaF toothpaste (675ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: <0.000195% CI: [382.41, 928.93]ANOVA
Comparison: Null hypothesis considered population means for AmF toothpaste (1400ppmF) and placebo toothpaste (0ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: <0.000195% CI: [1568.73, 2115.6]ANOVA
Comparison: Null hypothesis considered population means for the Na MFP/NaF toothpaste (1450ppmF) and NaF toothpaste (675ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: 0.244895% CI: [-110.58, 431.18]ANOVA
Comparison: Null hypothesis considered population means for the Na MFP/NaF toothpaste (1450ppmF) and Placebo toothpaste (0ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: <0.000195% CI: [1076.46, 1617.11]ANOVA
Comparison: Null hypothesis considered population means for the NaF toothpaste (675ppmF) and Placebo toothpaste (0ppmF) to be equal with respect to enamel fluoride uptake potential.p-value: <0.000195% CI: [915.38, 1457.6]ANOVA
Secondary
Percent SMH Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste (1400ppm F) and Placebo (0ppmF)
SMH test was used to assess the changes in 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. Differences in percent SMH recovery due to study and reference toothpastes were calculated.
Time frame: Baseline to 14 days
Population: PP population: All randomized participants who received at least one dose of the study treatments or provided at least one measurement SMH. Participants without any major protocol violations in given study treatment period were included in the PP population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NaF Toothpaste (1426ppmF) | Percent SMH Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste (1400ppm F) and Placebo (0ppmF) | 38.05 Percentage SMHR | Standard Error 2.52 |
| AmF Toothpaste (1400ppmF) | Percent SMH Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste (1400ppm F) and Placebo (0ppmF) | 41.06 Percentage SMHR | Standard Error 2.53 |
| NaMFP/NaF Toothpaste (1450ppmF) | Percent SMH Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste (1400ppm F) and Placebo (0ppmF) | 33.48 Percentage SMHR | Standard Error 2.49 |
| NaF Toothpaste (675ppmF) | Percent SMH Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste (1400ppm F) and Placebo (0ppmF) | 29.08 Percentage SMHR | Standard Error 2.5 |
| Placebo Toothpaste (0ppmF) | Percent SMH Recovery of Enamel Specimens Exposed to NaF Toothpaste (1426ppmF), NaF Toothpaste (675ppmF), NaMFP/NaF Toothpaste (1400ppm F) and Placebo (0ppmF) | 14.49 Percentage SMHR | Standard Error 2.48 |
Comparison: Null hypothesis considered population means for the NaF toothpaste (1426ppmF) and NaF toothpaste (675ppmF) to be equal with respect to enamel remineralization potential.p-value: 0.000295% CI: [4.27, 13.66]ANOVA
Comparison: Null hypothesis considered population means for the NaF toothpaste (1426ppmF) and Na MFP/NaF toothpaste (1450ppmF) to be equal with respect to enamel remineralization potential.p-value: 0.055795% CI: [-0.11, 9.24]ANOVA
Comparison: Null hypothesis considered population means for the NaF toothpaste (1426ppmF) and Placebo toothpaste (0ppmF) to be equal with respect to enamel remineralization potential.p-value: <0.000195% CI: [18.86, 28.24]ANOVA
Comparison: Null hypothesis considered population means for the Na MFP/NaF toothpaste (1450ppmF) and NaF toothpaste (675ppmF) to be equal with respect to enamel remineralization potential.p-value: 0.062595% CI: [-0.23, 9.03]ANOVA
Comparison: Null hypothesis considered population means for the Na MFP/NaF toothpaste (1450ppmF) and Placebo toothpaste (0ppmF) to be equal with respect to enamel remineralization potential.p-value: <0.000195% CI: [14.36, 23.61]ANOVA
Comparison: Null hypothesis considered population means for the NaF toothpaste (675ppmF) and Placebo toothpaste (0ppmF) to be equal with respect to enamel remineralization potential.p-value: <0.000195% CI: [9.95, 19.23]ANOVA
Comparison: Null hypothesis considered population means for the AmF toothpaste (1400ppmF) and Na MFP/NaF toothpaste (1450ppmF) to be equal with respect to enamel remineralization potential.p-value: 0.001795% CI: [2.88, 12.27]ANOVA
Comparison: Null hypothesis considered population means for AmF toothpaste (1400ppmF) and NaF toothpaste (675ppmF) to be equal with respect to enamel remineralization potential.p-value: <0.000195% CI: [7.31, 16.64]ANOVA
Comparison: Null hypothesis considered population means for AmF toothpaste (1400ppmF) and placebo toothpaste (0ppmF) to be equal with respect to enamel remineralization potential.p-value: <0.000195% CI: [21.88, 31.24]ANOVA