Trial Outcomes & Findings for Efficacy of Three Toothpastes Using an in Situ Caries Model (NCT NCT02751320)

Last Updated: 2017-10-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

58 participants

Primary outcome timeframe

Baseline upto 2 weeks

Results posted on

2017-10-13

Participant Flow

Participants were recruited at one center in United States.

A total of 58 participants were screened, of which 45 participants were randomized and 42 completed the study.

Participant milestones

Participant milestones
Measure	Overall Study This was a single-centre, randomized, blinded (examiner and laboratory analyst), placebo-controlled, 6-treatment, 4-period cross-over, incomplete block design, in situ caries study in healthy adults who wore a removable bilateral mandibular partial denture. Each participant received Test Product 1 (Dentifrice containing 0.425 % weight by weight (w/w) phytate, and 1150 parts per million \[ppm\] fluoride \[F\]), Test Product 2 (Dentifrice containing 0.85 % w/w phytate, and 1150 ppm fluoride), Test Product 3 (Dentifrice containing 0.85 % w/w phytate, 0.3% zinc chloride, 0.5% sodium citrate, and 1150 ppm fluoride), Reference Product 1 (0 ppm fluoride), Reference Product 2 (Dentrifrice containing 1150 ppm fluoride toothpaste and Reference Product 3 (Dentrifrice containing 0.3% zinc chloride , 0.5% sodium citrate, and 1150 ppm fluoride).
Overall Study STARTED	45
Overall Study Received Test Product 1	29
Overall Study Received Test Prodcut 2	28
Overall Study Received Test Prodcut 3	28
Overall Study Received Reference Product 1	29
Overall Study Received Reference Product 2	28
Overall Study Received Reference Product 3	28
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Overall Study This was a single-centre, randomized, blinded (examiner and laboratory analyst), placebo-controlled, 6-treatment, 4-period cross-over, incomplete block design, in situ caries study in healthy adults who wore a removable bilateral mandibular partial denture. Each participant received Test Product 1 (Dentifrice containing 0.425 % weight by weight (w/w) phytate, and 1150 parts per million \[ppm\] fluoride \[F\]), Test Product 2 (Dentifrice containing 0.85 % w/w phytate, and 1150 ppm fluoride), Test Product 3 (Dentifrice containing 0.85 % w/w phytate, 0.3% zinc chloride, 0.5% sodium citrate, and 1150 ppm fluoride), Reference Product 1 (0 ppm fluoride), Reference Product 2 (Dentrifrice containing 1150 ppm fluoride toothpaste and Reference Product 3 (Dentrifrice containing 0.3% zinc chloride , 0.5% sodium citrate, and 1150 ppm fluoride).
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Efficacy of Three Toothpastes Using an in Situ Caries Model

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Randomized Participants n=45 Participants All randomized participants were included for baseline evaluation.
Age, Continuous	64.3 Years STANDARD_DEVIATION 9.69 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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- \[1\].

Outcome measures

Outcome measures
Measure	Test Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.425 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15 milliliters (ml) of tap water for approximately 10 seconds (s).	Test Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.85 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 1 n=29 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 0 ppm fluoride) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 3 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F, 0.3% ZnCl2) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.
Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks	25.53 % SMHR Standard Deviation 21.513	26.81 % SMHR Standard Deviation 18.059	7.41 % SMHR Standard Deviation 18.648	28.88 % SMHR Standard Deviation 21.046	—	—

SECONDARY outcome

Timeframe: 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- \[1\].

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.

Outcome measures

Outcome measures
Measure	Test Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.425 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15 milliliters (ml) of tap water for approximately 10 seconds (s).	Test Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.85 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 0 ppm fluoride) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 3 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F, 0.3% ZnCl2) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.
% 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	23.38 % SMHR Standard Deviation 20.177	28.88 % SMHR Standard Deviation 21.046	28.80 % SMHR Standard Deviation 20.830	—	—

SECONDARY outcome

Timeframe: 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- \[1\].

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).

Outcome measures

Outcome measures
Measure	Test Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.425 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15 milliliters (ml) of tap water for approximately 10 seconds (s).	Test Product 2 n=27 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.85 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 1 n=29 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 0 ppm fluoride) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 3 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F, 0.3% ZnCl2) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.
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	2772.96 [%vol mineral x µm Standard Deviation 989.567	3849.83 [%vol mineral x µm Standard Deviation 1978.088	2720.00 [%vol mineral x µm Standard Deviation 1151.914	—	—

SECONDARY outcome

Timeframe: 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 \[1\].

Outcome measures

Outcome measures
Measure	Test Product 1 n=27 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.425 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15 milliliters (ml) of tap water for approximately 10 seconds (s).	Test Product 2 n=27 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.85 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 0 ppm fluoride) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 3 Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F, 0.3% ZnCl2) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.
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	2733.33 [%vol mineral x µm Standard Deviation 1051.738	2720.00 [%vol mineral x µm Standard Deviation 1151.914	2421.25 [%vol mineral x µm Standard Deviation 677.286	—	—

SECONDARY outcome

Timeframe: 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-\[1\].

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.

Outcome measures

Outcome measures
Measure	Test Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.425 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15 milliliters (ml) of tap water for approximately 10 seconds (s).	Test Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.85 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 0 ppm fluoride) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=29 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 3 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F, 0.3% ZnCl2) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.
Enamel Fluoride Uptake (EFU) of All Study Formulation Variables	5.35 μg/cm^2 Standard Deviation 2.038	4.78 μg/cm^2 Standard Deviation 2.655	5.02 μg/cm^2 Standard Deviation 2.499	1.09 μg/cm^2 Standard Deviation 0.397	5.87 μg/cm^2 Standard Deviation 2.772	5.37 μg/cm^2 Standard Deviation 2.384

SECONDARY outcome

Timeframe: 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-\[1\].

Outcome measures

Outcome measures
Measure	Test Product 1 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.425 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15 milliliters (ml) of tap water for approximately 10 seconds (s).	Test Product 2 n=27 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned experimental dentifrice (containing 0.85 % phytate, 1150 ppm F) for one timed minute twice daily, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 1 n=27 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 0 ppm fluoride) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=29 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned reference dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 2 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.	Reference Product 3 n=28 Participants Participants brushed their natural teeth with a pre-wetted toothbrush and their assigned dentifrice (containing 1150ppm F, 0.3% ZnCl2) for one timed minute, ensuring the enamel specimens retained within their mouths were not directly brushed. Participants then rinsed their mouths with 15ml of tap water for approximately 10s.
Enamel Fluoride Uptake (EFU) of All Study Formulation Variables	12.28 μg/cm^2 Standard Deviation 6.756	11.09 μg/cm^2 Standard Deviation 6.336	14.16 μg/cm^2 Standard Deviation 12.851	1.64 μg/cm^2 Standard Deviation 0.974	15.29 μg/cm^2 Standard Deviation 10.177	15.11 μg/cm^2 Standard Deviation 10.180

Adverse Events

Test Product 1

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths