Dental Caries
Conditions
Brief summary
This will be a single-centre, randomized, blinded, placebo-controlled, 6-treatment, 4-period crossover, incomplete block design, in situ caries study in healthy adults who wear a removable bilateral mandibular partial denture. The denture will be modified to accommodate 4 gauze-covered specimens of human dental enamel (4x3mm) that have been previously demineralized in vitro to form either S or low-R lesions (2 specimens of each lesion type will be used with each participant). After 14 days of twice daily product use off-site, the 2 S lesion specimens will be removed at the study site, with the remaining 2 low-R lesion specimens removed at the study site after a further 14 days of product use. To determine the remineralization ability of the treatments, all specimens will be analyzed by transverse microradiography (TMR) and enamel fluoride uptake (EFU), with the S lesions additionally analyzed by surface micro hardness (SMH) and the low-R lesions additionally analyzed by quantitative light fluorescence (QLF).
Interventions
DRUG0.425 % w/w phytate,1150ppm F
Participants were assigned with 1.5±0.1g twice daily dentifrice for one timed minute.
DRUG0.85 % w/w phytate,1150ppm F
Participants were assigned with 1.5±0.1g twice daily dentifrice for one timed minute.
DRUG0.85 % w/w phytate,0.3%ZnCl2 0.5% sodium citrate, 1150ppm F
Participants were assigned with 1.5±0.1g twice daily dentifrice for one timed minute.
OTHER0 ppm F
Participants were assigned with 1.5±0.1g twice daily dentifrice for one timed minute.
DRUG1150ppm F
Participants were assigned with 1.5±0.1g twice daily dentifrice for one timed minute.
DRUG0.3%ZnCl2, 0.5% sodium citrate, 1150ppm F
Participants were assigned with 1.5±0.1g twice daily dentifrice for one timed minute.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Demonstrates understanding of the study. 2. Aged 18 to 85 years. 3. Understands and is willing, able and likely to comply with all study procedures and restrictions. 4. Has good general health (in the opinion of the investigator or medically qualified designee). 5. A salivary flow-rate in the range of normal values (unstimulated whole saliva flow- Rate ≥ 0.2 g/minute (min); gum base stimulated whole saliva flow-Rate ≥ 0.8 g/min). 6. Currently wearing a removable mandibular partial denture with sufficient room in the posterior buccal flange area to accommodate two enamel specimens. 7. Have no current active caries or periodontal disease and all restorations in a good state of repair. 8. Willing and capable of brushing their natural teeth with the lower partial denture in place.
Exclusion criteria
1. Pregnant or breast feeding women. 2. Known or suspected intolerance or hypersensitivity to the study materials or their stated ingredients. 3. Currently taking antibiotics or have taken antibiotics in the two weeks prior to the screening visit. 4. Unable to measure product weights accurately using the assigned study scale as determined by the study staff as demonstrated. 5. Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit. 6. Have received a professional fluoride treatment within 14 days of randomization to the first treatment. 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 Phyte (0% 0.425% and 0.85%) at 2 Weeks | Baseline upto 2 weeks | SMHR test was used to assess the changes in mineralization status of partially demineralized enamel specimens using a Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. % SMHR was calculated from indentation length (micrometer \[μm\]) of sound enamel specimen at baseline (B), indentation length (μm) after in vitro demineralization(D), indentation length (μm) after intra-oral exposure (R): \[D-R/D-B\]\*100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate | Baseline upto 2 weeks | SMHR test was used to assess the changes in mineralization status of partially demineralized enamel specimens using a Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. % SMHR was calculated from indentation length (μm) of sound enamel specimen at baseline (B), indentation length (μm) after in vitro demineralization(D), indentation length (μm) after intra-oral exposure (R): \[D-R/D-B\]\*100. |
| Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks | Baseline upto 4 weeks | TMR was used to assess changes in the mineral status of partially demineralized enamel specimens. Lesions were analyzed at baseline and Integrated Mineral Loss (∆Z): (∆Z =(lesion depth x 87) - area under the curve \[Area under the curve which relates volume % mineral at distances from the specimen surface with respect to section thickness\]). After treatment a further section was taken from each lesion specimen for radiography assessment; ∆Z was calculated. The change which occurred in mineral content (∆M) of the lesions as a result of treatment was calculated by: ∆M= (baseline ∆Z - Post-treatment ∆Z). |
| TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate | Baseline upto 4 weeks | TMR was used to assess changes in the mineral status of partially demineralized enamel specimens. Lesions were analyzed at baseline and Integrated Mineral Loss (∆Z): (∆Z =(lesion depth x 87) - area under the curve \[Area under the curve which relates volume % mineral at distances from the specimen surface with respect to section thickness\]). After treatment a further section was taken from each lesion specimen for radiography assessment; ∆Z was calculated. The change which occurred in mineral content (∆M) of the lesions as a result of treatment was calculated by: ∆M= (baseline ∆Z - Post-treatment ∆Z). |
| Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | At Week 2 | 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 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 μg/cm\^2. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at one center in United States.
Pre-assignment details
A total of 58 participants were screened, of which 45 participants were randomized and 42 completed the study.
Participants by arm
| Arm | Count |
|---|---|
| All Randomized Participants All randomized participants were included for baseline evaluation. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | All Randomized Participants |
|---|---|
| Age, Continuous | 64.3 Years STANDARD_DEVIATION 9.69 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 24 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 20 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 | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 29 | 0 / 27 | 0 / 28 |
| other Total, other adverse events | 9 / 28 | 9 / 28 | 10 / 28 | 7 / 29 | 4 / 27 | 8 / 28 |
| serious Total, serious adverse events | 1 / 28 | 0 / 28 | 0 / 28 | 0 / 29 | 0 / 27 | 0 / 28 |
Outcome results
Primary
Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks
SMHR test was used to assess the changes in mineralization status of partially demineralized enamel specimens using a Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. % SMHR was calculated from indentation length (micrometer \[μm\]) of sound enamel specimen at baseline (B), indentation length (μm) after in vitro demineralization(D), indentation length (μm) after intra-oral exposure (R): \[D-R/D-B\]\*100.
Time frame: Baseline upto 2 weeks
Population: Intent-to-treat (ITT) population, all participants who were randomized, received the study products at least once and provided at least one post-baseline assessment of efficacy. Number of participants who missed enamel specimens were: Test product 1- \[1\], Test product 2- \[1\], Reference Product 1- \[1\], and Reference Product 2- \[1\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product 1 | Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks | 25.53 % SMHR | Standard Deviation 21.513 |
| Test Product 2 | Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks | 26.81 % SMHR | Standard Deviation 18.059 |
| Reference Product 1 | Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks | 7.41 % SMHR | Standard Deviation 18.648 |
| Reference Product 2 | Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks | 28.88 % SMHR | Standard Deviation 21.046 |
p-value: 0.760395% CI: [-8.11, 5.94]ANCOVA
p-value: 0.355595% CI: [-10.34, 3.74]ANCOVA
p-value: 0.533595% CI: [-4.81, 9.23]ANCOVA
Comparison: Treatment comparison corresponding to qualifying criteria for the analysisp-value: <0.000195% CI: [16.02, 29.9]ANCOVA
Secondary
Enamel Fluoride Uptake (EFU) of All Study Formulation Variables
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 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 μg/cm\^2.
Time frame: At Week 2
Population: ITT population, all participants who were randomized, received the study products at least once and provided at least one post-baseline assessment of efficacy. Number of participants who missed enamel specimens were: Test product1-\[1\], Test product2-\[1\], Test product3-\[2\], Reference Product1-\[1\], Reference Product2-\[1\] and Reference Product3-\[1\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product 1 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 5.35 μg/cm^2 | Standard Deviation 2.038 |
| Test Product 2 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 4.78 μg/cm^2 | Standard Deviation 2.655 |
| Reference Product 1 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 5.02 μg/cm^2 | Standard Deviation 2.499 |
| Reference Product 2 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 1.09 μg/cm^2 | Standard Deviation 0.397 |
| Reference Product 2 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 5.87 μg/cm^2 | Standard Deviation 2.772 |
| Reference Product 3 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 5.37 μg/cm^2 | Standard Deviation 2.384 |
Secondary
Enamel Fluoride Uptake (EFU) of All Study Formulation Variables
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 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 μg/cm\^2.
Time frame: At Week 4
Population: ITT population, all participants who were randomized, received the study products at least once and provided at least one post-baseline assessment of efficacy. Number of participants who missed enamel specimens were: Test product1-\[1\], Test product2-\[2\], Test product3-\[3\], Reference Product1-\[1\], Reference Product2-\[1\] and Reference Product3-\[1\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product 1 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 12.28 μg/cm^2 | Standard Deviation 6.756 |
| Test Product 2 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 11.09 μg/cm^2 | Standard Deviation 6.336 |
| Reference Product 1 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 14.16 μg/cm^2 | Standard Deviation 12.851 |
| Reference Product 2 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 1.64 μg/cm^2 | Standard Deviation 0.974 |
| Reference Product 2 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 15.29 μg/cm^2 | Standard Deviation 10.177 |
| Reference Product 3 | Enamel Fluoride Uptake (EFU) of All Study Formulation Variables | 15.11 μg/cm^2 | Standard Deviation 10.18 |
Secondary
% SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate
SMHR test was used to assess the changes in mineralization status of partially demineralized enamel specimens using a Wilson 2100 Hardness tester. SMH was determined by measuring the length of the indentations of enamel specimens. % SMHR was calculated from indentation length (μm) of sound enamel specimen at baseline (B), indentation length (μm) after in vitro demineralization(D), indentation length (μm) after intra-oral exposure (R): \[D-R/D-B\]\*100.
Time frame: Baseline upto 2 weeks
Population: ITT population, all participants who were randomized, received the study products at least once and provided at least one post-baseline assessment of efficacy. Number of participants who missed enamel specimens were: Test product 2- \[1\], Test product 3- \[2\], Reference Product 2- \[1\], and Reference Product 3- \[1\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product 1 | % SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate | 26.81 % SMHR | Standard Deviation 18.059 |
| Test Product 2 | % SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate | 23.38 % SMHR | Standard Deviation 20.177 |
| Reference Product 1 | % SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate | 28.88 % SMHR | Standard Deviation 21.046 |
| Reference Product 2 | % SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate | 28.80 % SMHR | Standard Deviation 20.83 |
Secondary
TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate
TMR was used to assess changes in the mineral status of partially demineralized enamel specimens. Lesions were analyzed at baseline and Integrated Mineral Loss (∆Z): (∆Z =(lesion depth x 87) - area under the curve \[Area under the curve which relates volume % mineral at distances from the specimen surface with respect to section thickness\]). After treatment a further section was taken from each lesion specimen for radiography assessment; ∆Z was calculated. The change which occurred in mineral content (∆M) of the lesions as a result of treatment was calculated by: ∆M= (baseline ∆Z - Post-treatment ∆Z).
Time frame: Baseline upto 4 weeks
Population: ITT population, all participants who were randomized, received the study products at least once and provided at least one post-baseline assessment of efficacy. Number of participants who missed enamel specimens were: Test product 2 - \[1\], Test product 3 - \[2\], Reference Product 2 - \[1\] and Reference Product 3 \[1\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product 1 | TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate | 2772.96 [%vol mineral x µm | Standard Deviation 989.567 |
| Test Product 2 | TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate | 2733.33 [%vol mineral x µm | Standard Deviation 1051.738 |
| Reference Product 1 | TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate | 2720.00 [%vol mineral x µm | Standard Deviation 1151.914 |
| Reference Product 2 | TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate | 2421.25 [%vol mineral x µm | Standard Deviation 677.286 |
Secondary
Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks
TMR was used to assess changes in the mineral status of partially demineralized enamel specimens. Lesions were analyzed at baseline and Integrated Mineral Loss (∆Z): (∆Z =(lesion depth x 87) - area under the curve \[Area under the curve which relates volume % mineral at distances from the specimen surface with respect to section thickness\]). After treatment a further section was taken from each lesion specimen for radiography assessment; ∆Z was calculated. The change which occurred in mineral content (∆M) of the lesions as a result of treatment was calculated by: ∆M= (baseline ∆Z - Post-treatment ∆Z).
Time frame: Baseline upto 4 weeks
Population: ITT population, all participants who were randomized, received the study products at least once and provided at least one post-baseline assessment of efficacy. Number of participants who missed enamel specimens were: Test product 1- \[1\], Test product 2- \[1\], and Reference Product 2- \[1\].
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test Product 1 | Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks | 3055.36 [%vol mineral x µm | Standard Deviation 1459.283 |
| Test Product 2 | Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks | 2772.96 [%vol mineral x µm | Standard Deviation 989.567 |
| Reference Product 1 | Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks | 3849.83 [%vol mineral x µm | Standard Deviation 1978.088 |
| Reference Product 2 | Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks | 2720.00 [%vol mineral x µm | Standard Deviation 1151.914 |