Evaluation of Oral Hygiene Products in an In Situ Caries Model

Study Overview
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Brief Summary
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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.

Official Title
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Clinical Evaluation of Oral Hygiene Products in an In Situ Caries Model

Conditions
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Dental Caries

Intervention / Treatment
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* Drug: Fluoride free toothpaste
* Drug: Fluoride toothpaste
* Drug: Fluoride mouthwash


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 85 years inclusive Understands and is willing, able and likely to comply with all study procedures and restrictions 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 Currently living in the Indianapolis, Indiana area and has not had a professional fluoride treatment within 14 days of the first treatment visit Currently wearing a removable mandibular partial denture with sufficient room in one posterior buccal flange areas to accommodate two enamel specimens 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 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: Pregnant or breast feeding women Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients Currently taking antibiotics or have taken antibiotics in the two weeks prior to the screening visit. Taking or have taken a bisphosphonate drug for treatment of osteoporosis. Participation in another GSKCH investigational dental product study within seven days of first study treatment. Previous participation in this study. Recent history (within the last year) of alcohol or other substance abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo dentifrice/Fluoride rinse<br>Twice daily brushing with a non-fluoride (placebo) toothpaste followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride | Drug: Fluoride free toothpaste<br>* Brushing with fluoride free toothpaste<br>Drug: Fluoride mouthwash<br>* 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<br>|
| Placebo Comparator: Placebo dentifrice/No rinse<br>Twice daily brushing with a non-fluoride (placebo) toothpaste | Drug: Fluoride free toothpaste<br>* Brushing with fluoride free toothpaste<br>|
| Active Comparator: Fluoride dentifrice/No rinse<br>Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride | Drug: Fluoride toothpaste<br>* Brushing with fluoride containing toothpaste<br>|
| Experimental: Fluoride dentifrice/Fluoride rinse<br>Twice daily brushing with a fluoride toothpaste containing 1150 ppm of fluoride as sodium fluoride, followed by once daily rinsing (post night time brushing) with a fluoride mouthwash containing 220 ppm of fluoride as sodium fluoride. | Drug: Fluoride toothpaste<br>* Brushing with fluoride containing toothpaste<br>Drug: Fluoride mouthwash<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to 14 days | 
| 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). | Baseline to 14 days | 
| 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. | Baseline to Day14 | 
| 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. | Baseline up to Day 14 |