Fluoride Retention in the Mouth of Older Adults

Optimizing Fluoride Retention in the Mouth of Older Adults With Distinct Salivary Flow Rates

Individuals with dry mouth (a reduction in the production of saliva) suffer from high rates of oral diseases. Dry mouth is a common problem among older individuals, because many medications to control chronic conditions (such as blood pressure, bladder-control problems and depression) reduce the flow of saliva. For these individuals, fluoride is used to maintain a good oral health. Usually, higher fluoride concentration products, such as prescription toothpastes, are recommended. In this project, the ability to increase fluoride retention in the mouth by using calcium before a conventional fluoride rinse will be tested in older adults with a range of salivary flow rates. This approach was never tested in patients with dry mouth, for whom the treatment with calcium may also be beneficial. A crossover, clinical study with two experimental phases will be conducted, in which patients with a range of saliva flows (from normal to dry mouth) will rinse with a fluoride rinse only (used at over the counter concentration), or a fluoride rinse preceded by a calcium rinse. The concentration of fluoride and calcium in the saliva and dental plaque residues will be determined up to two hours after the rinse(s), to test the effect of the approach to optimize fluoride retention in the mouth of patients with dry mouth.

Study Overview

• Status: Completed
• Conditions: Hyposalivation
• Intervention / Treatment: Drug: Fluoride mouthwash; Drug: Calcium and fluoride mouthwash

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • School of Dentistry, University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Good general health as evidenced by medical history
• Good oral health as evidenced by a clinical oral exam
• Having at least 20 teeth in the mouth, being at least 4 (natural or crowned) teeth in all four quadrants of the mouth
• Having salivary flow rate ranging from normal to hyposalivation according to direct flow rate determination methods
• Agreement to adhere to the study protocol

Exclusion Criteria:

• Unable to understand and/or follow study instructions
• Active periodontitis
• Oral pain
• In need of urgent dental care

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluoride mouthwash alone, then Calcium mouthwash before a fluoride mouthwash; Participants with normal to dry mouth will first test a Fluoride mouthwash containing 226 ppm of fluoride, and fluoride concentration in saliva and dental biofilm will be assessed overtime for up to 2 hours. After a washout period of at least 3 days, they will then test a Calcium mouthwash (150 milimolars of calcium) immediately before the Fluoride mouthwash, and fluoride concentration in saliva and dental biofilm will be assessed overtime for up to 2 hours.	Drug: Fluoride mouthwash; Sodium fluoride, at a concentration of 0.05% (226 parts per million (ppm) of fluoride), will be used to rinse the mouth for 1 minute and expectorated.; Other Names: Fluoride rinse; Drug: Calcium and fluoride mouthwash; Calcium lactate, at a concentration of 150 milimolar, will be used to rinse the mouth for 1 minute and expectorated; immediately after, a sodium fluoride rinse, at a concentration of 0.05% (226 ppm of fluoride), will be used to rinse the mouth for 1 minute, and expectorated.; Other Names: Calcium and fluoride rinse
Experimental: Calcium mouthwash before a fluoride mouthwash, then Fluoride mouthwash alone; Participants with normal to dry mouth will first test a Calcium mouthwash (150 milimolars of calcium) immediately before a Fluoride mouthwash containing 226 ppm of fluoride, and fluoride concentration in saliva and dental biofilm will be assessed overtime for up to 2 hours. After a washout period of at least 3 days, they will then test the Fluoride mouthwash alone, and fluoride concentration in saliva and dental biofilm will be assessed overtime for up to 2 hours.	Drug: Fluoride mouthwash; Sodium fluoride, at a concentration of 0.05% (226 parts per million (ppm) of fluoride), will be used to rinse the mouth for 1 minute and expectorated.; Other Names: Fluoride rinse; Drug: Calcium and fluoride mouthwash; Calcium lactate, at a concentration of 150 milimolar, will be used to rinse the mouth for 1 minute and expectorated; immediately after, a sodium fluoride rinse, at a concentration of 0.05% (226 ppm of fluoride), will be used to rinse the mouth for 1 minute, and expectorated.; Other Names: Calcium and fluoride rinse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluoride Concentration in Dental Biofilm Fluid at Baseline	Dental biofilm was collected at baseline (before mouthwash(es)), and the fluid phase was separated using centrifugation. Fluoride concentration in the dental biofilm fluid was measured using an ion-specific electrode adapted for microanalysis.	Baseline
Fluoride Concentration in Dental Biofilm Fluid at 15 Minutes	Dental biofilm was collected 15 minutes after mouthwash(es), and the fluid phase was separated using centrifugation. Fluoride concentration in the dental biofilm fluid was measured using an ion-specific electrode adapted for microanalysis.	15 minutes after mouthwash(es)
Fluoride Concentration in Dental Biofilm Fluid at 60 Minutes	Dental biofilm was collected 60 minutes after mouthwash(es), and the fluid phase was separated using centrifugation. Fluoride concentration in the dental biofilm fluid was measured using an ion-specific electrode adapted for microanalysis.	60 minutes after mouthwash(es)
Fluoride Concentration in Dental Biofilm Fluid at 120 Minutes	Dental biofilm was collected 120 minutes after mouthwash(es), and the fluid phase was separated using centrifugation. Fluoride concentration in the dental biofilm fluid was measured using an ion-specific electrode adapted for microanalysis.	120 minutes after mouthwash(es)
Fluoride Concentration in Dental Biofilm Solids at Baseline	Dental biofilm was collected at baseline (before mouthwash(es)). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of fluoride reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Fluoride concentration in the dental biofilm solids acid extract was measured using an ion-specific electrode adapted for microanalysis; protein concentration in the alkali extract was determined using the Lowry colorimetric method. Fluoride concentration in the biofilm was expressed as micrograms of fluoride/milligrams of protein.	Baseline
Fluoride Concentration in Dental Biofilm Solids at 15 Minutes	Dental biofilm was collected 15 minutes after mouthwash(es). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of fluoride reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Fluoride concentration in the dental biofilm solids acid extract was measured using an ion-specific electrode adapted for microanalysis; protein concentration in the alkali extract was determined using the Lowry colorimetric method. Fluoride concentration in the biofilm was expressed as micrograms of fluoride/milligrams of protein.	15 minutes after mouthwash(es)
Fluoride Concentration in Dental Biofilm Solids at 60 Minutes	Dental biofilm will be collected 60 minutes after mouthwash(es). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of fluoride reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Fluoride concentration in the dental biofilm solids acid extract was measured using an ion-specific electrode adapted for microanalysis; protein concentration in the alkali extract was determined using the Lowry colorimetric method. Fluoride concentration in the biofilm was expressed as micrograms of fluoride/milligrams of protein.	60 minutes after mouthwash(es)
Fluoride Concentration in Dental Biofilm Solids at 120 Minutes	Dental biofilm was collected 120 minutes after mouthwash(es). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of fluoride reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Fluoride concentration in the dental biofilm solids acid extract was measured using an ion-specific electrode adapted for microanalysis; protein concentration in the alkali extract was determined using the Lowry colorimetric method. Fluoride concentration in the biofilm was expressed as micrograms of fluoride/milligrams of protein.	120 minutes after mouthwash(es)
Area Under the Curve of Fluoride Concentration in Dental Biofilm Fluid Overtime	Fluoride concentration in dental biofilm fluid collected at baseline (before mouthwash(es)), 15, 60 and 120 minutes after mouthwash(es) was expressed as the area under the curve of fluoride concentration in dental biofilm fluid as a function of time (parts per million x min).	Baseline, 15, 60 and 120 minutes after mouthwash(es)
Area Under the Curve of Fluoride Concentration in Dental Biofilm Solids Overtime	Fluoride concentration in dental biofilm solids collected at baseline (before mouthwash(es)), 15, 60 and 120 minutes after mouthwash(es) was expressed as the area under the curve of fluoride concentration in dental biofilm solids as a function of time (micrograms of fluoride x minutes/ milligram of proteins).	Baseline, 15, 60 and 120 minutes after mouthwash

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluoride Concentration in Saliva at Baseline	Unstimulated saliva was collected at baseline (before mouthwash(es)), for 5 minutes. Fluoride concentration in unstimulated saliva was measured using an ion-specific electrode adapted for microanalysis.	Baseline
Fluoride Concentration in Saliva at 16 Minutes	Unstimulated saliva was collected 16 minutes after mouthwash(es), for 5 minutes. Fluoride concentration in unstimulated saliva was measured using an ion-specific electrode adapted for microanalysis.	16-21 minutes after mouthwash(es)
Fluoride Concentration in Saliva at 30 Minutes	Unstimulated saliva was collected 30 minutes after mouthwash(es), for 5 minutes. Fluoride concentration in unstimulated saliva was measured using an ion-specific electrode adapted for microanalysis.	30-35 minutes after mouthwash(es)
Fluoride Concentration in Saliva at 61 Minutes	Unstimulated saliva was collected 61 minutes after mouthwash(es), for 5 minutes. Fluoride concentration in unstimulated saliva was measured using an ion-specific electrode adapted for microanalysis.	61-66 minutes after mouthwash(es)
Fluoride Concentration in Saliva at 90 Minutes	Unstimulated saliva was collected 90 minutes after mouthwash(es), for 5 minutes. Fluoride concentration in unstimulated saliva was measured using an ion-specific electrode adapted for microanalysis.	90-95 minutes after mouthwash(es)
Fluoride Concentration in Saliva at 121 Minutes	Unstimulated saliva was collected 121 minutes after mouthwash(es), for 5 minutes. Fluoride concentration in unstimulated saliva was measured using an ion-specific electrode adapted for microanalysis.	121-126 minutes after mouthwash(es)
Calcium Concentration in Dental Biofilm Fluid at Baseline	Dental biofilm will be collected at baseline (before mouthwash(es)), and the fluid phase will be separated using centrifugation. Calcium concentration in the dental biofilm fluid will be measured using an ion-specific electrode adapted for microanalysis, and will be expressed in millimolar.	Baseline
Calcium Concentration in Dental Biofilm Fluid at 15 Minutes	Dental biofilm will be collected 15 minutes after mouthwash(es), and the fluid phase will be separated using centrifugation. Calcium concentration in the dental biofilm fluid will be measured using an ion-specific electrode adapted for microanalysis, and will be expressed in millimolar.	15 minutes after mouthwash(es)
Calcium Concentration in Dental Biofilm Fluid at 60 Minutes	Dental biofilm will be collected 60 minutes after mouthwash(es), and the fluid phase will be separated using centrifugation. Calcium concentration in the dental biofilm fluid will be measured using an ion-specific electrode adapted for microanalysis, and will be expressed in millimolar.	60 minutes after mouthwash(es)
Calcium Concentration in Dental Biofilm Fluid at 120 Minutes	Dental biofilm will be collected 120 minutes after mouthwash(es), and the fluid phase will be separated using centrifugation. Calcium concentration in the dental biofilm fluid will be measured using an ion-specific electrode adapted for microanalysis, and will be expressed in millimolar.	120 minutes after mouthwash(es)
Calcium Concentration in Dental Biofilm Solids at Baseline	Dental biofilm was collected at baseline (before mouthwash(es)). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of calcium reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Calcium concentration in the dental biofilm solids acid extract was measured using a colorimetric reaction (Arsenazo III); protein concentration in the alkali extract was determined using the Lowry colorimetric method. Calcium concentration in the biofilm was expressed as micrograms of calcium/milligrams of protein.	Baseline
Calcium Concentration in Dental Biofilm Solids at 15 Minutes	Dental biofilm was collected 15 minutes after mouthwash(es). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of calcium reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Calcium concentration in the dental biofilm solids acid extract was measured using a colorimetric reaction (Arsenazo III); protein concentration in the alkali extract was determined using the Lowry colorimetric method. Calcium concentration in the biofilm was expressed as micrograms of calcium/milligrams of protein.	15 minutes after mouthwash(es)
Calcium Concentration in Dental Biofilm Solids at 60 Minutes	Dental biofilm was collected 60 minutes after mouthwash(es). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of calcium reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Calcium concentration in the dental biofilm solids acid extract was measured using a colorimetric reaction (Arsenazo III); protein concentration in the alkali extract was determined using the Lowry colorimetric method. Calcium concentration in the biofilm was expressed as micrograms of calcium/milligrams of protein.	60 minutes after mouthwash(es)
Calcium Concentration in Dental Biofilm Solids at 120 Minutes	Dental biofilm was collected 120 minutes after mouthwash(es). The fluid phase of the biofilm was collected after centrifugation, and the remaining solids were treated with strong acid for dissolution of calcium reservoirs. Solids remaining after acid extraction were treated with strong alkali for total dissolution of the biofilm and estimation of biofilm mass by protein concentration. Calcium concentration in the dental biofilm solids acid extract was measured using a colorimetric reaction (Arsenazo III); protein concentration in the alkali extract was determined using the Lowry colorimetric method. Calcium concentration in the biofilm was expressed as micrograms of calcium/milligrams of protein.	120 minutes after mouthwash(es)
Calcium Concentration in Saliva at Baseline	Unstimulated saliva was collected at baseline (before mouthwash(es)), for 5 minutes. Calcium concentration in unstimulated saliva was measured using a colorimetric reaction (Arsenazo III).	Baseline
Calcium Concentration in Saliva at 16 Minutes	Unstimulated saliva was collected at 16 minutes after mouthwash(es), for 5 minutes. Calcium concentration in unstimulated saliva was measured using a colorimetric reaction (Arsenazo III).	16-21 minutes after mouthwash(es)
Calcium Concentration in Saliva at 30 Minutes	Unstimulated saliva was collected at 30 minutes after mouthwash(es), for 5 minutes. Calcium concentration in unstimulated saliva was measured using a colorimetric reaction (Arsenazo III).	30-35 minutes after mouthwash(es)
Calcium Concentration in Saliva at 61 Minutes	Unstimulated saliva was collected at 61 minutes after mouthwash(es), for 5 minutes. Calcium concentration in unstimulated saliva was measured using a colorimetric reaction (Arsenazo III).	61-66 minutes after mouthwash(es)
Calcium Concentration in Saliva at 90 Minutes	Unstimulated saliva was collected at 90 minutes after mouthwash(es), for 5 minutes. Calcium concentration in unstimulated saliva was measured using a colorimetric reaction (Arsenazo III).	90-95 minutes after mouthwash(es)
Calcium Concentration in Saliva at 121 Minutes	Unstimulated saliva was collected at 121 minutes after mouthwash(es), for 5 minutes. Calcium concentration in unstimulated saliva was measured using a colorimetric reaction (Arsenazo III).	121-126 minutes after mouthwash(es)
Area Under the Curve of Fluoride Concentration in Saliva Overtime	Fluoride concentration in unstimulated saliva collected at baseline (before mouthwash(es)), 16, 30, 61, 90 and 121 minutes after mouthwash(es) was expressed as the area under the curve of fluoride concentration in saliva as a function of time.	Baseline, 16, 30, 61, 90 and 121 minutes after mouthwash(es)
Area Under the Curve of Calcium Concentration in Dental Biofilm Fluid Overtime	Calcium concentration in dental biofilm fluid collected at baseline (before mouthwash(es)), 15, 60 and 120 minutes after mouthwash(es) will be expressed as the area under the curve of calcium concentration in dental biofilm fluid as a function of time (millimolar x min).	Baseline, 15, 60 and 120 minutes after mouthwash(es)
Area Under the Curve of Calcium Concentration in Dental Biofilm Solids Overtime	Calcium concentration in dental biofilm solids collected at baseline (before mouthwash(es)), 15, 60 and 120 minutes after mouthwash(es) was expressed as the area under the curve of calcium concentration in dental biofilm solids as a function of time.	Baseline, 15, 60 and 120 minutes after mouthwash(es)
Area Under the Curve of Calcium Concentration in Saliva Overtime	Calcium concentration in unstimulated saliva collected at baseline (before mouthwash(es)), 16, 30, 61, 90 and 121 minutes after mouthwash(es) was expressed as the area under the curve of calcium concentration in saliva as a function of time (millimolar x min).	Baseline, 16, 30, 61, 90 and 121 minutes after a mouthwash(es)

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Livia M Tenuta, DDS, MS, PhD, Associate Professor, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2020
• Primary Completion (Actual): April 5, 2021
• Study Completion (Actual): April 5, 2021

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 20, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Xerostomia; Physiological Effects of Drugs; Protective Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Cariostatic Agents; Calcium; Fluorides; Calcium, Dietary
• Other Study ID Numbers: HUM00159624; UL1TR002240 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No