An in Situ Study on the Impact of Fluoride Dose and Concentration in Milk on Its Anti-caries Efficacy

Study Overview
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Brief Summary
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The study will be randomized, investigator-blind, observer-blind, laboratory analyst-blind and will utilize a 5-way cross-over study design with a primary objective to determine if a higher dose of fluoride in milk will provide a greater caries preventive effect. Secondary objectives are to determine in a higher concentration of fluoride in milk will provide a greater caries preventive effect and if the caries preventive effect of fluoridated milk follows a dose-response pattern.

Detailed Description
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The evidence of milk fluoridation as a public health measure in caries prevention has been demonstrated in many clinical studies. While these data are encouraging, the main focus now should be on the optimization of milk fluoride programs. This protocol will concentrate on the parameters of fluoride dose and concentration utilizing an in situ model, the intra-oral caries test or model (ICT). The ICT is an established model which features the use of gauze-covered specimens to facilitate plaque growth and to simulate a caries-prone/plaque stagnation area. After subject has been consented and enrolled in the study per the inclusion/exclusion criteria, two to three days following a dental cleaning, two partially demineralized specimens will be placed in the buccal flange area of the subject's mandibular partial denture. During each of the five, three-week test periods, subjects will drink their assigned milk test product once per day for either five (100 ml milk) or ten (200 ml milk) timed minutes, wearing their mandibular partial dentures 24 hours a day during the test period. Fluoride free toothpaste will be used two to three days before and continuously during each treatment period. After each three-week test period, the two partially demineralized specimens will be removed from the subject's partial denture and analyzed using the surface microhardness test. Mineral content change (as percentage of surface microhardness recovery) in these artificially induced incipient enamel lesions will be the primary outcome variable. Each subject (n = 28) will serve as his or her own control.

Official Title
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An in Situ Study on the Impact of Fluoride Dose and Concentration in Milk on Its Anti-caries Efficacy

Conditions
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Caries

Intervention / Treatment
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* Drug: 1.5 mg Sodium Fluoride in 100 ml milk
* Drug: 1.5 mg sodium fluoride in 200 ml milk
* Drug: 3 mg sodium fluoride in 100 ml milk
* Drug: 3 mg sodium fluoride in 200 ml milk
* Other: Non-fluoridated milk, 200 ml


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sign an informed consent, authorization for the release of health information for research and provide medical history information, including medications, prior to their participation; be between 18 and 80 years old and in general good health; willingness to use a reliable form of contraception or abstaining during the course of the study (females of child-bearing potential only) wear a removable mandibular partial denture with sufficient room in one posterior buccal flange area to accommodate two enamel specimens (required dimensions 12×7 mm); be willing and capable of wearing their removable mandibular partial dentures 24 hours a day for a total of five, three-week test periods; be in good dental health with no active caries or periodontal disease; agree to comply with all subjects' responsibilities as stated in the protocol (e.g. use of study products, attendance at appointments, etc.); 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). Be able to tolerate the taste and room temperature of the mixed milk product as demonstrated by drinking the milk at screening Exclusion Criteria: be pregnant, intending to become pregnant during the study period or breast feeding. A urine pregnancy test will be required at screening, the start of each treatment visit and the last study visit for all subjects of child-bearing potential to confirm the subject is not pregnant. have any medical condition that could be expected to interfere with the subject's safety during the study period; demonstrate an inability to comply with study procedures; have factors which could contraindicate their participation, such as any condition requiring the need for antibiotic premedication prior to a dental treatment, a condition requiring the need for long-term antibiotic use, blood thinning medications that prohibit the safe conduct of a dental cleaning* or previous use of the weight loss medications Fen Phen® or Redux®. (*Note: Subjects who are taking blood thinners in which written verification is obtained from their physician indicating their PT/INR levels (anti-coagulation blood levels) are at an acceptable level to avoid serious complications, such as bleeding during dental cleanings, may be accepted into the study at the discretion of the Investigator.) be currently taking or have ever taken a bisphosphonate drug (i.e. Fosamax®, Actonel®, Boniva®, Reclast®, or Zometa®) for treatment of osteoporosis. be lactose intolerant or have known allergy or intolerance to milk or milk products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm 1<br>non-fluoridated milk, 200 ml 1.5 mg sodium fluoride in 100 ml milk, 1.5 mg sodium fluoride in 200 ml milk, 3 mg sodium fluoride in 100 ml milk, 3 mg sodium fluoride in 200 ml milk | Drug: 1.5 mg Sodium Fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 1.5 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Other: Non-fluoridated milk, 200 ml<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk;|
| Other: Arm 2<br>non-fluoridated milk, 200 ml 1.5 mg sodium fluoride in 100 ml milk, 1.5 mg sodium fluoride in 200 ml milk, 3 mg sodium fluoride in 100 ml milk, 3 mg sodium fluoride in 200 ml milk | Drug: 1.5 mg Sodium Fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 1.5 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Other: Non-fluoridated milk, 200 ml<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk;|
| Other: Arm 3<br>non-fluoridated milk, 200 ml 1.5 mg sodium fluoride in 100 ml milk, 1.5 mg sodium fluoride in 200 ml milk, 3 mg sodium fluoride in 100 ml milk, 3 mg sodium fluoride in 200 ml milk | Drug: 1.5 mg Sodium Fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 1.5 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Other: Non-fluoridated milk, 200 ml<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk;|
| Other: Arm 4<br>non-fluoridated milk, 200 ml 1.5 mg sodium fluoride in 100 ml milk, 1.5 mg sodium fluoride in 200 ml milk, 3 mg sodium fluoride in 100 ml milk, 3 mg sodium fluoride in 200 ml milk | Drug: 1.5 mg Sodium Fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 1.5 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Other: Non-fluoridated milk, 200 ml<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk;|
| Active Comparator: Arm 5<br>non-fluoridated milk, 200 ml 1.5 mg sodium fluoride in 100 ml milk, 1.5 mg sodium fluoride in 200 ml milk, 3 mg sodium fluoride in 100 ml milk, 3 mg sodium fluoride in 200 ml milk | Drug: 1.5 mg Sodium Fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 1.5 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 100 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Drug: 3 mg sodium fluoride in 200 ml milk<br>* Each subject will use this product during one of the five treatment periods in the crossover study design<br>* Other names: Kroger Nonfat Dry Milk reconstituted with fluoride-free milk;Other: Non-fluoridated milk, 200 ml<br>* Each subject will use this product during one of the five treatment periods in the crossover study design.<br>* Other names: Kroger Nonfat Dry Milk;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % Surface Microhardness (SMH) Recovery Score Per Each of Five Arms | surface microhardness recovery is a measure of caries lesion remineralization and is calculated using the following equation: SMHr=(D1-R)/(D1-B)×100 B = indentation length of sound enamel specimen at baseline D1 = indentation length after first in vitro demineralization R = indentation length after intra-oral exposure (rehardening). | Three Weeks per each of five arms | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % Acid Resistance Score Per Each of Five Arms | % Acid Resistance is a measure of acid resistance of the remineralized caries lesion which is calculated as (D1-D2)/(D1-B)*100%, where B is the indentation length of sound enamel specimen at baseline, D1 is an indentation length after first in vitro demineralization, D2 is an indentation length after second in vitro demineralization. | Three Weeks per each of five arms | 
| Enamel Fluoride Uptake Per Each of Five Arms | Enamel fluoride uptake is a measure of fluoridation of a caries lesion | Three Weeks per each of five arms | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Caries