Effect of Chewing a Calcium Supplement Before Fluoride Rinse on Salivary Fluoride

• ClinicalTrials.gov Identifier: NCT04620252
• Recruitment Status: Completed
• First Posted: November 6, 2020
• Last Update Posted: May 9, 2022
• Sponsor: University of Michigan
• Information provided by (Responsible Party): Livia Tenuta, University of Michigan

Tracking Information

• First Submitted Date: November 5, 2020
• First Posted Date: November 6, 2020
• Last Update Posted Date: May 9, 2022
• Actual Study Start Date: February 1, 2021
• Actual Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 2, 2022)

• Calcium concentration in saliva at baseline [ Time Frame: Baseline ]
  Saliva collected as one spit, immediately before chewing one of the calcium supplements to be tested in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in the mixture of saliva and chewed calcium supplement [ Time Frame: Immediately after the 30-second chewing of calcium supplement ]
  Saliva and remnants of the chewed calcium supplement collected at the end of the chewing period (30 seconds) in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 15 seconds [ Time Frame: 15 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 15 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 30 seconds [ Time Frame: 30 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 30 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 45 seconds [ Time Frame: 45 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 45 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 60 seconds [ Time Frame: 60 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 60 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 120 seconds [ Time Frame: 120 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 120 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 180 seconds [ Time Frame: 180 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 180 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 240 seconds [ Time Frame: 240 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 240 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Calcium concentration in saliva at 300 seconds [ Time Frame: 300 seconds after chewing calcium supplement ]
  Saliva collected as one spit, 300 seconds after chewing the calcium supplement in Arm 1. Calcium concentration determined using a colorimetric method.
• Area under the curve of calcium concentration in saliva [ Time Frame: Baseline, 15, 30, 45, 60, 120, 180, 240 and 300 seconds after chewing calcium supplements ]
  Calcium concentration in saliva collected at baseline (before chewing the supplements), and 15, 30, 45, 60, 120, 180, 240 and 300 seconds after chewing the supplements in Arm 1 expressed as the area under the curve of calcium concentration in saliva as a function of time (milimolar x min).
• Fluoride concentration in saliva at baseline [ Time Frame: Baseline ]
  Saliva will be collected for 2 min, immediately before chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at time 0 [ Time Frame: 0 minutes after chewing supplement/mouthwashing ]
  Saliva and remnants of the fluoride mouth rinse collected at the end of the rinsing period (1 minute) in Arm 2. Fluoride concentration determined using an ion-specific electrode.
• Fluoride concentration in saliva at 5 min [ Time Frame: 5 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 5 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at 15 min [ Time Frame: 15 minutes after chewing supplement/mouthwashing ]
  Saliva collected for 2 min, 15 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration determined using an ion-specific electrode.
• Fluoride concentration in saliva at 30 min [ Time Frame: 30 minutes after chewing supplement/mouthwashing ]
  Saliva collected for 2 min, 30 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration determined using an ion-specific electrode.
• Fluoride concentration in saliva at 60 min [ Time Frame: 60 minutes after chewing supplement/mouthwashing ]
  Saliva collected for 2 min, 60 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration determined using an ion-specific electrode.
• Fluoride concentration in saliva at 120 min [ Time Frame: 120 minutes after chewing supplement/mouthwashing ]
  Saliva collected for 2 min, 120 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration determined using an ion-specific electrode.
• Area under the curve of fluoride concentration in saliva [ Time Frame: Baseline, 5, 15, 30, 60 and 120 minutes after chewing supplement/mouthwashing ]
  Fluoride concentration in saliva collected at baseline (before treatments), and 0, 5, 15, 30, 60 and 120 minutes after chewing the supplements and/or rinsing the fluoride mouthrinse in Arm 2 expressed as the area under the curve of fluoride concentration in saliva as a function of time (micromolar x min).

Original Primary Outcome Measures (submitted: November 5, 2020)

• Calcium concentration in saliva at baseline [ Time Frame: Baseline ]
  Saliva will be collected as one spit, immediately before chewing one of the calcium supplements to be tested in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in the mixture of saliva and chewed calcium supplement [ Time Frame: Immediately after the 30-second chewing of calcium supplement ]
  Saliva and remnants of the chewed calcium supplement will be will be collected at the end of the chewing period (30 seconds) in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 15 seconds [ Time Frame: 15 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 15 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 30 seconds [ Time Frame: 30 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 30 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 45 seconds [ Time Frame: 45 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 45 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 60 seconds [ Time Frame: 60 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 60 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 120 seconds [ Time Frame: 120 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 120 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 180 seconds [ Time Frame: 180 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 180 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 240 seconds [ Time Frame: 240 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 240 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 300 seconds [ Time Frame: 300 seconds after chewing calcium supplement ]
  Saliva will be collected as one spit, 300 seconds after chewing the calcium supplement in Arm 1. Calcium concentration will be determined using a colorimetric method.
• Area under the curve of calcium concentration in saliva [ Time Frame: Baseline, 15, 30, 45, 60, 120, 180, 240 and 300 seconds after chewing calcium supplements ]
  Calcium concentration in saliva collected at baseline (before chewing the supplements), and 15, 30, 45, 60, 120, 180, 240 and 300 seconds after chewing the supplements in Arm 1 will be expressed as the area under the curve of calcium concentration in saliva as a function of time (milimolar x min).
• Fluoride concentration in saliva at baseline [ Time Frame: Baseline ]
  Saliva will be collected for 2 min, immediately before chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at time 0 [ Time Frame: 0 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, immediately after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at 5 min [ Time Frame: 5 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 5 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at 15 min [ Time Frame: 15 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 15 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at 30 min [ Time Frame: 30 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 30 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at 60 min [ Time Frame: 60 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 60 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Fluoride concentration in saliva at 120 min [ Time Frame: 120 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 120 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Fluoride concentration will be determined using an ion-specific electrode.
• Area under the curve of fluoride concentration in saliva [ Time Frame: Baseline, 0, 5, 15, 30, 60 and 120 minutes after chewing supplement/mouthwashing ]
  Fluoride concentration in saliva collected at baseline (before treatments), and 0, 5, 15, 30, 60 and 120 minutes after chewing the supplements and/or rinsing the fluoride mouthrinse in Arm 2 will be expressed as the area under the curve of fluoride concentration in saliva as a function of time (micromolar x min).

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: November 5, 2020)

• Calcium concentration in saliva at baseline [ Time Frame: Baseline ]
  Saliva will be collected for 2 min, immediately before chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at time 0 [ Time Frame: 0 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, immediately after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 5 minutes [ Time Frame: 5 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 5 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 15 minutes [ Time Frame: 15 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 15 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 30 minutes [ Time Frame: 30 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 30 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 60 minutes [ Time Frame: 60 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 60 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Calcium concentration will be determined using a colorimetric method.
• Calcium concentration in saliva at 120 minutes [ Time Frame: 120 minutes after chewing supplement/mouthwashing ]
  Saliva will be collected for 2 min, 120 min after chewing a calcium supplement and/or rinse with the fluoride mouthrinse in Arm 2. Calcium concentration will be determined using a colorimetric method.
• Area under the curve of calcium concentration in saliva [ Time Frame: Baseline, 0, 5, 15, 30, 60 and 120 minutes after chewing supplement/mouthwashing ]
  Calcium concentration in saliva collected at baseline (before treatments), and 0, 5, 15, 30, 60 and 120 minutes after chewing the supplements and/or rinsing the fluoride mouthrinse in Arm 2 will be expressed as the area under the curve of calcium concentration in saliva as a function of time (milimolar x min).

Descriptive Information

• Brief Title: Effect of Chewing a Calcium Supplement Before Fluoride Rinse on Salivary Fluoride
• Official Title: Enhancing the Fluoride Retention in the Mouth by Chewing a Calcium Supplement Before Fluoride Rinse
• Brief Summary: The anticaries effect of fluoride is through the increase in fluoride presence and retention in the oral fluids, reducing dental demineralization and enhancing remineralization. Previous studies showed that a preapplication of calcium (in a rinse) prior to administration of fluoride greatly enhances fluoride concentration in the mouth and the anticaries effect of fluoride. The hypothesis of this study is that the same can be achieved by chewing a calcium supplement prior to a fluoride rinse. The first goal is to determine if chewing these calcium supplements will increase calcium concentration in the oral fluids above baseline levels. Secondly, the calcium supplement with the highest calcium release will be tested before a fluoride rinse to assess the increased retention of fluoride in the oral fluids when compared with the fluoride rinse alone. In both parts, healthy volunteers will participate and saliva will be collected to assess calcium and fluoride concentration.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Prevention
• Condition: Dental Caries

Intervention

• Drug: Inactive supplement
  Chewable candy (negative control), chewed for 30 seconds.
• Drug: Tricalcium phosphate supplement
  Chewable tricalcium phosphate supplement, chewed for 30 seconds.
• Drug: Calcium carbonate supplement
  Chewable calcium carbonate supplement, chewed for 30 seconds.
• Drug: Calcium citrate supplement
  Chewable calcium citrate supplement, chewed for 30 seconds.
• Drug: Inactive supplement and fluoride mouthwash
  A chewable candy chewed for 30 seconds, immediately followed by a 1 minute rinse with an over the counter sodium fluoride mouthwash, at a concentration of 0.05% (226 parts per millim (ppm) of fluoride).
• Drug: Calcium carbonate supplement and fluoride mouthwash
  A calcium carbonate supplement chewed for 30 seconds, immediately followed by a 1 minute rinse with an over the counter sodium fluoride mouthwash, at a concentration of 0.05% (226 parts per millim (ppm) of fluoride).
• Drug: Calcium citrate supplement and fluoride mouthwash
  A calcium citrate supplement chewed for 30 seconds, immediately followed by a 1 minute rinse with an over the counter sodium fluoride mouthwash, at a concentration of 0.05% (226 parts per millim (ppm) of fluoride).

Study Arms

• Experimental: Chewing calcium supplements

  Participants were given one of 4 different treatments to chew: a negative control group and 3 calcium supplements with different calcium compositions.

  Participants were randomized to determine the sequence of exposure to the different treatments.

  Interventions:

  • Drug: Inactive supplement
  • Drug: Tricalcium phosphate supplement
  • Drug: Calcium carbonate supplement
  • Drug: Calcium citrate supplement
• Experimental: Fluoride rinse
  Participants rinsed with an over the counter sodium fluoride rinse for 1 min, after having chewed a candy (negative control), a calcium calcium carbonate or a calcium citrate supplement.
  Interventions:

  • Drug: Inactive supplement and fluoride mouthwash
  • Drug: Calcium carbonate supplement and fluoride mouthwash
  • Drug: Calcium citrate supplement and fluoride mouthwash

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 2, 2022): 18
• Original Estimated Enrollment (submitted: November 5, 2020): 35
• Actual Study Completion Date: March 31, 2022
• Actual Primary Completion Date: March 31, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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
• Reported good general health
• Reported good oral health
• Having at least 20 teeth in the mouth, being at least 4 (natural or crowned) teeth in all four quadrants of the mouth
• Having normal salivary flow rate according to direct flow rate determination methods
• Agreement to adhere to the study protocol

Exclusion Criteria:

• Unable to understand and/or follow study instructions
• Hyposalivation
• Active periodontitis, identified by frequent bleeding of the gums
• Oral pain
• In need of urgent dental care

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04620252
• Other Study ID Numbers: HUM00176242
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Livia Tenuta, University of Michigan
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Michigan
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Michigan
• Verification Date: May 2022