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

This study has been completed.
Sponsor:
Collaborator:
The Borrow Foundation
Information provided by (Responsible Party):
Frank Lippert, Indiana University School of Dentistry
ClinicalTrials.gov Identifier:
NCT01665911
First received: August 7, 2012
Last updated: September 2, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention
Caries
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Official Title: An in Situ Study on the Impact of Fluoride Dose and Concentration in Milk on Its Anti-caries Efficacy

Resource links provided by NLM:


Further study details as provided by Indiana University School of Dentistry:

Primary Outcome Measures:
  • % Surface Microhardness (SMH) Recovery Score Per Each of Five Arms [ Time Frame: Three Weeks per each of five arms ] [ Designated as safety issue: No ]
    • 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).


Secondary Outcome Measures:
  • % Acid Resistance Score Per Each of Five Arms [ Time Frame: Three Weeks per each of five arms ] [ Designated as safety issue: No ]
    % 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.

  • Enamel Fluoride Uptake Per Each of Five Arms [ Time Frame: Three Weeks per each of five arms ] [ Designated as safety issue: No ]
    Enamel fluoride uptake is a measure of fluoridation of a caries lesion


Enrollment: 28
Study Start Date: August 2012
Study Completion Date: June 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm 1
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
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 1.5 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 100 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Other: Non-fluoridated milk, 200 ml
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Name: Kroger Nonfat Dry Milk
Arm 2
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
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 1.5 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 100 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Other: Non-fluoridated milk, 200 ml
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Name: Kroger Nonfat Dry Milk
Arm 3
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
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 1.5 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 100 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Other: Non-fluoridated milk, 200 ml
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Name: Kroger Nonfat Dry Milk
Arm 4
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
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 1.5 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 100 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Other: Non-fluoridated milk, 200 ml
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Name: Kroger Nonfat Dry Milk
Active Comparator: Arm 5
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
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 1.5 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 100 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Drug: 3 mg sodium fluoride in 200 ml milk
Each subject will use this product during one of the five treatment periods in the crossover study design
Other Names:
  • sodium fluoride (PCCA Sodium Fluoride USP 51927-1038-00)
  • Kroger Nonfat Dry Milk reconstituted with fluoride-free milk
Other: Non-fluoridated milk, 200 ml
Each subject will use this product during one of the five treatment periods in the crossover study design.
Other Name: Kroger Nonfat Dry Milk

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01665911

Locations
United States, Indiana
Oral Health Research Institute, Indiana University School of Dentistry
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Frank Lippert
The Borrow Foundation
Investigators
Principal Investigator: Frank Lippert, PhD Indiana University School of Dentistry
Principal Investigator: Domenick Zero, DDS, MS Indiana University School of Dentistry
  More Information

Publications:
Responsible Party: Frank Lippert, Assistant Research Professor, Indiana University School of Dentistry
ClinicalTrials.gov Identifier: NCT01665911     History of Changes
Other Study ID Numbers: 12-I-086
Study First Received: August 7, 2012
Results First Received: August 5, 2014
Last Updated: September 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University School of Dentistry:
Caries

Additional relevant MeSH terms:
Fluorides
Listerine
Sodium Fluoride
Anti-Infective Agents
Anti-Infective Agents, Local
Cariostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014