Evaluation of the Fluoride Dose Response of a Modified In Situ Caries Model

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03383783

Enrollment

Registered

2017-12-26

Start date

2017-12-19

Completion date

2018-05-02

Last updated

2019-05-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Caries

Keywords

Caries

Brief summary

The purpose of this study is to evaluate the fluoride dose response of different dentifrice fluoride concentrations - 0, 250, 500 and 1100 ppm fluoride of our existing in situ model involving the use of human enamel specimens placed in the buccal flange area of the subjects partial denture with the modified model involving placement of bovine enamel specimens in a denture tooth location.

Detailed description

This will be a double blind, single center, 4-way crossover design study involving 34 adult subjects, between the ages of 18 and 85 years. Two to three days before the start of each treatment period the subjects will have their teeth cleaned to remove all accessible plaque and calculus and will be provided with a non-fluoride dentifrice to use until their next visit. At the beginning of each testing period, two gauze-covered 4 × 4 mm partially demineralized human enamel specimens will be placed in the buccal flange area of the subject's mandibular partial denture. In addition, two gauze-covered 4 mm round partially demineralized bovine enamel specimens will be placed in the buccal surface of two posterior denture teeth of the same side of the partial denture. Once specimens are placed, subjects will wear their partial dentures twenty-four hours a day and use their assigned toothpaste twice daily, as instructed, until their next visit. Specimens will be removed after two weeks and the subjects will undergo a four to five day washout period followed by another cleaning and two to three day lead in period. This process will be repeated until all subjects have used all four test products. Changes in the mineral content of the enamel specimens will be assessed using the SMH and TMR. Enamel fluoride uptake (EFU) will be determined using the microdrill enamel biopsy technique. In addition the net acid resistance (NAR) and the comparative acid resistance (CAR) of the remineralized enamel specimens will be determined.

Interventions

DRUG0 ppm F (placebo, negative control)

Each subject will use this product during one of the four treatment periods in the crossover study design.

DRUG250 ppm F as NaF (dose-response control)

Each subject will use this product during one of the four treatment periods in the crossover study design.

DRUG500 ppm F as NaF (dose-response control)

Each subject will use this product during one of the four treatment periods in the crossover study design.

DRUG1100 ppm F as NaF (positive control)

Each subject will use this product during one of the four treatment periods in the crossover study design.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

DOUBLE (Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

Healthy volunteers

Yes

Inclusion criteria

1. provide voluntary, written informed consent; 2. be between 18 and 85 years old; 3. understand and be willing, able and likely to comply with all study procedures and restrictions; 4. be wearing a removable mandibular partial denture with sufficient room in one posterior buccal flange area to accommodate two enamel specimens (required dimensions 12 × 7 mm) and room on the same side to accommodate two 4 mm round specimens in the buccal surface of two posterior denture teeth; 5. be willing and capable of wearing their removable partial denture 24 hours a day for four (4), two-week treatment periods; 6. be willing to allow study personnel to drill specimen sites (as described #4) in their mandibular partial denture; 7. be in good medical and dental health with no active caries or periodontal disease; NOTE; subjects presenting at screening with caries may continue in the study if their carious lesions are restored prior to beginning treatment 1. 8. have a salivary flow rate in the range of normal values (unstimulated whole saliva flow rate ≥ 0.2 mL/min; gum base stimulated whole saliva flow rate ≥ 0.8 mL/min).

Exclusion criteria

1. currently be pregnant, intending to become pregnant during the study period or breast feeding; 2. currently have any medical condition that could be expected to interfere with the subject's safety during the study period; 3. currently be taking antibiotics or have taken antibiotics in the two weeks prior to the beginning treatment 1; 4. have participated in another clinical study or receipt of an investigational drug within 30 days of beginning treatment 1; or 5. be taking fluoride supplements, required to use a fluoride mouthrinse or have received a professional fluoride treatment in the two weeks preceding specimen placement; 6. be taking or have ever taken bisphosphonate drugs (e.g., Fosamax, Actonel and Boniva) for the treatment of osteoporosis;

Design outcomes

Primary

Measure	Time frame	Description
Percentage Surface Microhardness Recovery (%SMH)	Enamel specimens will be evaluated after 14 days of intra-oral exposure	The extent of remineralization will be calculated based on the method of \[Gelhard et al., 1979\]. * SMH recovery = (D1-R)/(D1-B) ×100 B = indentation length (µm) of sound enamel specimen at baseline D1 = indentation length (µm) after in vitro demineralization R = indentation length (µm) after intra-oral exposure.

Secondary

Measure	Time frame	Description
Comparative Acid Resistance (CAR)	Enamel specimens will be evaluated after 14 days of intra-oral exposure	Using the data from the four centrally located enamel specimens, the equation used will compare explicitly the reduction in SMH brought by the first and second acid challenges: * Comparative Acid Resistance = \[(D2-R) / (D1-B)\] \* 100 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 in vitro demineralization D2= Indentation length (µm) after second in vitro demineralization
Enamel Fluoride Uptake (EFU)	Enamel specimens will be evaluated after 14 days of intra-oral exposure	The amount of fluoride-uptake by enamel will be calculated based on the amount of fluoride divided by the area of the enamel cores and expressed as µg F/cm2.
Net Acid Resistance (NAR)	Enamel specimens will be evaluated after 14 days of intra-oral exposure	The %NAR will be calculated by the method of Corpron \[Corpron et al., 1986\]: * Net Acid Resistance = \[(D1-D2) / (D1-B)\] \* 100 B= Indentation length (µm) of sound enamel at baseline D1= Indentation length (µm) after first in vitro demineralization D2= Indentation length (µm) after second in vitro demineralization
Transverse Microradiography (TMR) - Lesion Depth - L	Enamel specimens will be evaluated after 14 days of intra-oral exposure	Lesions will be analyzed after in situ demineralization and the following three parameters calculated: 1. Integrated Mineral Loss - ∆Z= \[(lesion depth x 87) - area under the curve\*\] 2. Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) 3. Maximum mineral density at the surface-zone - SZmax
Transverse Microradiography (TMR) - Maximum Mineral Density at the Surface-zone	Enamel specimens will be evaluated after 14 days of intra-oral exposure	Lesions will be analyzed after in situ demineralization and the following three parameters calculated: 1. Integrated Mineral Loss - ∆Z= \[(lesion depth x 87) - area under the curve\*\] 2. Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) 3. Maximum mineral density at the surface-zone - SZmax (arbitrary unit from TMR software)
Transverse Microradiography (TMR) - Integrated Mineral Loss - ∆Z	Enamel specimens will be evaluated after 14 days of intra-oral exposure	Lesions will be analyzed after in situ demineralization and the following three parameters calculated: 1. Integrated Mineral Loss - ∆Z= \[(lesion depth x 87) - area under the curve\*\] 2. Lesion Depth - L (83% mineral i.e. 95% of the mineral content of sound enamel) 3. Maximum mineral density at the surface-zone - SZmax

Countries

United States

Participant flow

Pre-assignment details

1 participant signed the informed consent and attended up to visit 2, but were dropped from the study as they no longer met inclusion criteria, and this occurred before randomization to interventions.

Participants by arm

Arm	Count
All Study Participants This was a 4-way crossover design study. All participants were randomized to receive the following interventions: Dentifrice fluoride concentrations - 0, 250, 500 and 1100 ppm fluoride of our existing in situ model involving the use of human enamel specimens placed in the buccal flange area of the subjects partial denture with the modified model involving placement of bovine enamel specimens in a denture tooth location.	27
Total	27

Arm

Count

All Study Participants

This was a 4-way crossover design study. All participants were randomized to receive the following interventions: Dentifrice fluoride concentrations - 0, 250, 500 and 1100 ppm fluoride of our existing in situ model involving the use of human enamel specimens placed in the buccal flange area of the subjects partial denture with the modified model involving placement of bovine enamel specimens in a denture tooth location.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	All Study Participants
Age, Continuous	67 Years
Race/Ethnicity, Customized African-American	14 Participants
Race/Ethnicity, Customized White	12 Participants
Race/Ethnicity, Customized White/African-American	1 Participants
Region of Enrollment United States	27 Participants
Sex: Female, Male Female	18 Participants
Sex: Female, Male Male	9 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 / 27	0 / 27	0 / 27	0 / 27	0 / 27	0 / 28
other Total, other adverse events	10 / 27	5 / 27	6 / 27	5 / 27	7 / 27	18 / 28
serious Total, serious adverse events	0 / 27	0 / 27	0 / 27	0 / 27	0 / 27	0 / 28

Outcome results

Primary

Percentage Surface Microhardness Recovery (%SMH)

The extent of remineralization will be calculated based on the method of \[Gelhard et al., 1979\]. * SMH recovery = (D1-R)/(D1-B) ×100 B = indentation length (µm) of sound enamel specimen at baseline D1 = indentation length (µm) after in vitro demineralization R = indentation length (µm) after intra-oral exposure.