Dental Caries
Conditions
Brief summary
The study will evaluate and compare the potential anti-caries efficacy of a test regimen: placebo (fluoride free) toothpaste (twice daily use) plus fluoride mouthwash (once daily use), in comparison with brushing with a placebo toothpaste alone (twice daily use), to remineralize previously demineralized enamel specimens, as measured by Surface MicroHardness Recovery (%SMHR). This will be a single center, randomized, laboratory analyst blinded, placebo, four treatment, cross-over study in healthy participants. Participants will be assessed at baseline and at the beginning and end of each treatment visit to monitor clinical efficacy and safety.
Interventions
Brushing with fluoride free toothpaste
DRUGFluoride toothpaste
Brushing with fluoride containing toothpaste
Fluoride mouth wash to be followed after brushing with fluoride free toothpaste in Placebo dentifrice/Fluoride rinse arm and in Fluoride dentifrice/Fluoride rinse arm
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Aged between 18 and 85 years inclusive 2. Understands and is willing, able and likely to comply with all study procedures and restrictions 3. Good general and mental health with, in the opinion of the investigator or medically qualified designee: * No clinically significant and relevant abnormalities in medical history or upon oral examination. * Absence of any condition that could affect the participant's safety or well-being or their ability to understand and follow study procedures and requirements 4. Currently living in the Indianapolis, Indiana area and has not had a professional fluoride treatment within 14 days of the first treatment visit 5. Currently wearing a removable mandibular partial denture with sufficient room in one posterior buccal flange areas to accommodate two enamel specimens 6. Willing to have their denture modified to accommodate enamel test specimens and willing and capable of wearing their removable mandibular partial dentures 24 hours per day during the experimental periods 7. Have a salivary flow rate in the range of normal values (un-stimulated whole saliva flow rate ≥ 0.2 milliliter (mL)/minute; gum base stimulated whole saliva flow rate ≥ 0.8 mL/minute).
Exclusion criteria
1. Pregnant or breast feeding women 2. Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients 3. Currently taking antibiotics or have taken antibiotics in the two weeks prior to the screening visit. 4. Taking or have taken a bisphosphonate drug for treatment of osteoporosis. 5. Participation in another GSKCH investigational dental product study within seven days of first study treatment. 6. Previous participation in this study. 7. Recent history (within the last year) of alcohol or other substance abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Surface Microhardness Recovery (%SMHR) of Placebo Dentifrice/Fluoride Rinse Compared to Placebo Dentifrice/No Rinse | Baseline to 14 days | SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer \[μm\]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): \[D1-R/D1-B\]\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse | Baseline to 14 days | SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer \[μm\]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): \[D1-R/D1-B\]\*100. |
| Enamel Fluoride Uptake | Baseline to 14 days | 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 samples 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). |
| Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14 | Baseline to Day14 | Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 baseline prior to supervised treatment. - at day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample. |
| Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14 | Baseline up to Day 14 | Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at one center in United States of America.
Pre-assignment details
A total of 80 participants were screened. Of the 80 participants, 62 were randomized and 53 completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Overall Participants All randomized participants were evaluated for baseline characteristics | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Protocol Deviation | 2 |
| Overall Study | Withdrawal by Participant | 5 |
Baseline characteristics
| Characteristic | Overall Participants |
|---|---|
| Age, Continuous | 64.1 Years STANDARD_DEVIATION 10.45 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 30 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Sex: Female, Male Female | 35 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 |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 60 | 13 / 56 | 18 / 59 | 17 / 57 |
| serious Total, serious adverse events | 1 / 60 | 1 / 56 | 0 / 59 | 1 / 57 |
Outcome results
Primary
Percentage Surface Microhardness Recovery (%SMHR) of Placebo Dentifrice/Fluoride Rinse Compared to Placebo Dentifrice/No Rinse
SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer \[μm\]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): \[D1-R/D1-B\]\*100.
Time frame: Baseline to 14 days
Population: Per-protocol (PP) population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Dentifrice/Fluoride Rinse | Percentage Surface Microhardness Recovery (%SMHR) of Placebo Dentifrice/Fluoride Rinse Compared to Placebo Dentifrice/No Rinse | 24.48 % SMHR | Standard Deviation 16.088 |
| Placebo Dentifrice/No Rinse | Percentage Surface Microhardness Recovery (%SMHR) of Placebo Dentifrice/Fluoride Rinse Compared to Placebo Dentifrice/No Rinse | 8.09 % SMHR | Standard Deviation 25.892 |
p-value: <0.000195% CI: [11.061, 22.454]ANCOVA
Secondary
Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14
Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample.
Time frame: Baseline up to Day 14
Population: PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Dentifrice/Fluoride Rinse | Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14 | 13.08 μg/mL | Standard Deviation 9.743 |
| Placebo Dentifrice/No Rinse | Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14 | 0.05 μg/mL | Standard Deviation 0.045 |
| Fluoride Dentifrice/No Rinse | Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14 | 8.62 μg/mL | Standard Deviation 6.892 |
| Fluoride Dentifrice/Fluoride Rinse | Change in Saliva Fluoride Concentration From Baseline (Post-treatment) to Day 14 | 13.81 μg/mL | Standard Deviation 10.62 |
Secondary
Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14
Fluoride concentration in saliva was measured after collecting saliva samples at the following time points: - at Day 1 baseline prior to supervised treatment. - at day 1 post supervised treatment at site. - at Day 14 post treatment. The amount of fluoride in the samples was calculated based on the amount of fluoride divided by the volume of the sample and expressed as μg/mL of sample.
Time frame: Baseline to Day14
Population: PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Dentifrice/Fluoride Rinse | Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14 | 0.06 microgram per mililitre(μg/mL ) | Standard Deviation 0.317 |
| Placebo Dentifrice/No Rinse | Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14 | -0.01 microgram per mililitre(μg/mL ) | Standard Deviation 0.03 |
| Fluoride Dentifrice/No Rinse | Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14 | 0.00 microgram per mililitre(μg/mL ) | Standard Deviation 0.245 |
| Fluoride Dentifrice/Fluoride Rinse | Change in Saliva Fluoride Concentration From Baseline (Pre-treatment) to Day 14 | 0.06 microgram per mililitre(μg/mL ) | Standard Deviation 0.203 |
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 samples 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 14 days
Population: PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Dentifrice/Fluoride Rinse | Enamel Fluoride Uptake | 7.22 microgram per square centimeter(μg/cm^2) | Standard Deviation 3.016 |
| Placebo Dentifrice/No Rinse | Enamel Fluoride Uptake | 1.60 microgram per square centimeter(μg/cm^2) | Standard Deviation 0.67 |
| Fluoride Dentifrice/No Rinse | Enamel Fluoride Uptake | 8.01 microgram per square centimeter(μg/cm^2) | Standard Deviation 3.925 |
| Fluoride Dentifrice/Fluoride Rinse | Enamel Fluoride Uptake | 9.97 microgram per square centimeter(μg/cm^2) | Standard Deviation 4.962 |
Secondary
Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse
SMHR test was used to assess the changes in mineralization status of enamel specimens using a Wilson 2100 Hardness tester. SMHR was performed ex-vivo and 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. % SMH recovery was calculated from indentation length (micrometer \[μm\]) of sound enamel specimen at baseline(B), indentation length (μm) after in vitro demineralization(D1), indentation length (μm) after intra-oral exposure (R): \[D1-R/D1-B\]\*100.
Time frame: Baseline to 14 days
Population: PP population included all participants who were randomized into the study, received at least one dose of study product, had at least one post-baseline efficacy assessment and had no protocol violations deemed to affect efficacy during the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Dentifrice/Fluoride Rinse | Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse | 24.48 % SMHR | Standard Deviation 16.088 |
| Placebo Dentifrice/No Rinse | Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse | 8.09 % SMHR | Standard Deviation 25.892 |
| Fluoride Dentifrice/No Rinse | Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse | 28.36 % SMHR | Standard Deviation 21.037 |
| Fluoride Dentifrice/Fluoride Rinse | Percentage Surface Microhardness Recovery (SMHR) of Placebo Dentifrice/Fluoride Rinse, Placebo Dentifrice/No Rinse, Fluoride Dentifrice/No Rinse and Fluoride Dentifrice/Fluoride Rinse | 30.01 % SMHR | Standard Deviation 18.203 |