CAGP-F: Effect of Calcium Glycerophosphate (CaGP) - Fluoride Dentifrice on Dental Biofilm pH

• Sponsor: Federal University of Paraíba (Other)
• Overall Status: Completed
• CT.gov ID: NCT00875212
• Collaborator: Conselho Nacional de Desenvolvimento Científico e Tecnológico (Other), Coordination for the Improvement of Higher Education Personnel (Other)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 30
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The aim of this study was to investigate the buffering effect of a calcium glycerophosphate-fluoride (CaGP-F) dentifrice on in vivo dental biofilm after a cariogenic challenge and evaluate its probable 12-hour protective effect. Twelve young adults took part in this randomized, double blind, 14-day 4-phase crossover study. Between each phase, the volunteers had a 1-week wash-out period. Coded dentifrices were randomly assigned to the volunteers: A) no F and no CaGP; B) CaGP-only (0.13%); C) F-only (1500 ppm (ppm= parts per million of fluoride which is equivalent to mg/kg)); D) CaGP-F (0.13%, 1500 ppm, respectively). The pH measurements were taken from a single-site using a microelectrode, with salt bridge established by a 1M KCl (one molar potassium chloride) solution with a reference electrode. pH measurements were taken at 0 (baseline), 1, 7, 14 and 21 min (minutes) after a cariogenic challenge (10% w/v sucrose solution, %w/v = percent weight per volume). Four sets of measurements were carried out: (D0BS) before test dentifrice usage; (D01min) 1-min after test dentifrice usage; and (D712h) 7 days and (D1412h) 14 days using the test dentifrice, 12 hours (h)after brushing. Stephen curves and mean AUC (area under the curve) were obtained.

Condition or Disease	Intervention/Treatment	Phase
Dental Caries	Drug: calcium glycerophosphate; Drug: no active ingredient; Drug: fluoride; Drug: CAGP + fluoride	Phase 1

Detailed Description

Although the mechanisms of action of fluoride are reasonably understood, the mechanism of calcium phosphate and calcium glycerophosphate (CaGP) are still a matter of debate. It has been suggested that CaGP increases the phosphorus content in the biofilm and, as a result, the buffering capacity of the biofilm is intensified. The pH levels of the biofilm are maintained above the 5.0-5.5 range. This is above the critical range for enamel demineralization.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: Effect of a Dentifrice Containing Calcium Glycerophosphate and Fluoride on the pH of Dental Biofilm in Vivo
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: dentifrice intervention 4 types of dentifrices were used in 4 different periods in a crossover study design.

Drug: calcium glycerophosphate; use of a dentifrice containing CaGP (0.13%) and no fluoride; Other Names: CaGP ; Drug: no active ingredient; dentifrice without calcium glycerophosphate and no fluoride; Other Names: dentifrice only (placebo) ; Drug: fluoride; use of a dentifrice containing fluoride (1500ppm) only; Other Names: sodium fluoride ; Drug: CAGP + fluoride; calcium glycerophosphate and fluoride dentifrice; Other Names: Experimental dentifrice with CAGP + fluoride

Outcome Measures

Primary Outcome Measures

1. Minimum pH [at 1 minute (minimum fermenting pH) or at 7 minutes]

   The dental biofilm pH was measured in vivo with the microtouch method, using a palladium microelectrode + reference electrode. Data represents the mean values of the lowest pH observed each time after the use of sucrose.

2. Minimum pH After 14 Days of Use of Dentifrice [14 days]

   measurement of pH obtained as described before. However, this time the biofilm was exposed to the dentifrices for a longer period (14 days).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• to live in a non-fluoridated area

• to have at least 20 natural teeth

• signed a consent form agreeing to carefully follow the research instructions

Exclusion Criteria:

• presence of active caries lesions

• periodontal disease

• use of antibiotics/medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Health Science Centre at the Federal University of Paraiba	Joao Pessoa	Paraiba	Brazil	58051900

Sponsors and Collaborators

• Federal University of Paraíba
• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Coordination for the Improvement of Higher Education Personnel

Investigators

• Principal Investigator: Fabio C Sampaio, PhD, Federal University of Paraiba
• Study Chair: Thiago S Carvalho, Master, Federal University of Paraiba

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00875212
• Other Study ID Numbers: UFPB-CAPES_2005; CNPq?PIBIC?UFPB_2005
• First Posted: Apr 3, 2009
• Last Update Posted: Oct 15, 2009
• Last Verified: Oct 1, 2009

• Keywords provided by , ,: Calcium glycerophosphate; Fluoride; Dentifrice; Biofilm; Dental caries
• Additional relevant MeSH terms: Dental Caries; Calcium; Fluorides; Sodium Fluoride

Study Results

Participant Flow

Recruitment Details	The subjects were dental students of the University. The recruitment locations were dental clinics of the faculty and laboratory facilities. The dates of recruitment included 2-3 months before starting the research in January 2006; and lasted for 2 months afterwards
Pre-assignment Detail	As a pre-assignment procedure, all volunteers signed an informed consent. The the volunteers received a dental hygiene kit containing a toothbrush and a fluoride-free and calcium-free dentifrice as part of the 1-week wash-out period prior to group assignment.

Arm/Group Title	Toothbrushing
Arm/Group Description	The study was based on the use of dentifrices for daily oral hygiene in a crossover design. The volunteers were asked to use the placebo and test dentifrices for one week. During the study, the volunteers were instructed to brush their teeth normally until 3 days before the measurements. During these 3 days, they were instructed to brush only the occlusal surfaces of their teeth until 12 hours before the pH measurements, when they should stop brushing altogether for dental plaque pH evaluation.
Period Title: Placebo Dentifrice
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: Placebo Dentifrice
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: Placebo Dentifrice
STARTED	12
COMPLETED	12
NOT COMPLETED	0
Period Title: Placebo Dentifrice
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Toothbrushing
Arm/Group Description	The study was based on the use of dentifrices for daily oral hygiene in a crossover design. The volunteers were asked to use the placebo and test dentifrices for one week. During the study, the volunteers were instructed to brush their teeth normally until 3 days before the measurements. During these 3 days, they were instructed to brush only the occlusal surfaces of their teeth until 12 hours before the pH measurements, when they should stop brushing altogether for dental plaque pH evaluation.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26 (3)
Sex: Female, Male (Count of Participants)
Female	6 50%
Male	6 50%
Region of Enrollment (participants) [Number]
Brazil	12 100%

Outcome Measures

1. Primary Outcome

Title	Minimum pH
Description	The dental biofilm pH was measured in vivo with the microtouch method, using a palladium microelectrode + reference electrode. Data represents the mean values of the lowest pH observed each time after the use of sucrose.
Time Frame	at 1 minute (minimum fermenting pH) or at 7 minutes

Outcome Measure Data

Analysis Population Description

The number of subjects were determined by a pilot study carried out in 3 volunteers. The study has a crossover design. Thus the 4 groups of dentifrices tested included the same subjects in a different time-measurement avoiding the influence of individual variables in the analysis.

Arm/Group Title	Control	Calcium Glycerophosphate	Fluoride	Calcium Glycerophosphate and Fluoride
Arm/Group Description	intervention of using a dentifrice of no active ingredient. The volunteers were asked to use the placebo dentifrices for one week. Throughout the study, the volunteers were instructed to brush their teeth normally up until 3 days before the measurements. During these 3 days, they were instructed to brush only the occlusal surfaces of their teeth until 12 hours before the pH measurements, when they should stop brushing altogether for dental plaque pH evaluation.	intervention of using a dentifrice containing only calcium glycerophosphate (CaGP)	intervention of using a dentifrice with 1,500 ppm of fluoride	intervention of using a dentifrice containing fluoride and calcium glycerophosphate
Measure Participants	12	12	12	12
Mean (Standard Deviation) [pH]	5.40 (0.60)	5.48 (0.65)	5.25 (0.77)	5.70 (0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Calcium Glycerophosphate, Fluoride, Calcium Glycerophosphate and Fluoride
	Comments	The study was based on the use of dentifrices for daily oral hygiene in a crossover design. The null hyphothesis was no difference between pH values of the groups. The statistical analysis was by repeated measurements ANOVA.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANOVA
	Comments	repeated measure anova
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	5.5
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.25
	Estimation Comments	The median value of each parameter (pH baseline, minimal pH) was obtained and these values were compared between each group

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Control, Calcium Glycerophosphate, Fluoride, Calcium Glycerophosphate and Fluoride
	Comments	The comparison was based on mean and median values of plaque pH in different moments of cariogenic challenge. The null hypothesis was that no diference between the groups wil be found. The test hypothesis was that the experimental dentifrice of CaGP-F would provide a better control of plaque pH after 14 days of use.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANOVA
	Comments	repeated-measurements ANOVA
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	5.5
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.1
	Estimation Comments

2. Primary Outcome

Title	Minimum pH After 14 Days of Use of Dentifrice
Description	measurement of pH obtained as described before. However, this time the biofilm was exposed to the dentifrices for a longer period (14 days).
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

The initial part of the work as a pilot study.

Arm/Group Title	Control	Calcium Glycerophosphate	Fluoride	Calcium Glycerophosphate and Fluoride
Arm/Group Description	use of a placebo dentifrice (no fluoride and no CaGP). The volunteers were asked to use the placebo dentifrices for more one week. Throughout the study, the volunteers were instructed to brush their teeth normally up until 3 days before the measurements. During these 3 days, they were instructed to brush only the occlusal surfaces of their teeth until 12 hours before the pH measurements, when they should stop brushing altogether for dental plaque pH evaluation.	intervention of using a CaGP dentifrice	intrvention of using a 1,500 ppm fluoridated dentifrice	intervention of using a CaGP+Fluoride dentifrice
Measure Participants	12	12	12	12
Mean (Standard Deviation) [pH]	4.78 (0.67)	5.24 (0.83)	5.25 (0.71)	5.44 (0.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Calcium Glycerophosphate, Fluoride, Calcium Glycerophosphate and Fluoride
	Comments	The groups were compared by repeated measurements anova. There was no power calculation, but a pilot study to check the minimal number necessary of subjects in order to find a signifcant difference between interventions.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	ANOVA
	Comments	repeated measurements ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.5
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.25
	Estimation Comments	The difference of pH values between groups was above 1.0 unit.

Adverse Events

Arm/Group Title	Toothbrushing
Arm/Group Description	The study was based on the use of dentifrices for daily oral hygiene in a crossover design. The volunteers were asked to use the placebo and test dentifrices for one week. During the study, the volunteers were instructed to brush their teeth normally until 3 days before the measurements. During these 3 days, they were instructed to brush only the occlusal surfaces of their teeth until 12 hours before the pH measurements, when they should stop brushing altogether for dental plaque pH evaluation.
All Cause Mortality
	Toothbrushing
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Toothbrushing
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Toothbrushing
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

pH measurements of dental biofilms were difficult after continuous use of dentifrice because of reduced biofilm mass in contrast to baseline measurements.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.