Dentifrice With Innovative Remineralizing Technology: a Randomized Clinical Study (REFIX)

• ClinicalTrials.gov Identifier: NCT04730908
• Recruitment Status: Recruiting
• First Posted: January 29, 2021
• Last Update Posted: January 29, 2021
• Sponsor: Federal University of Paraíba
• Information provided by (Responsible Party): Fabio Correia Sampaio, Federal University of Paraíba

Study Description

Brief Summary:

Objective: The aim of this study is to evaluate in vivo dentifrices containing different active ingredients in fluoride (F) retention in saliva and dental biofilm. Material and methods: The dentifrices used in the study were: G1- Daily Regenerator Dentalclean Neutral (RDCN); G2- Sensodyne Repair & Protect (SRP); G3- Daily Regenerator Dentalclean Acid (RDCA), G4- Colgate Total Daily Repairc (CTDR). A double-blind, randomized crossover clinical study was conducted with eighteen residents of a city without a water fluoridation program. Biofilm and saliva samples were collected 1h and 12h after the last brushing for biofilm and, 1 to 60 minutes and 12 hours for saliva. The concentrations of F in saliva and biofilm were analyzed by specific electrode using the hexamethyldisiloxane facilitated diffusion technique (HMDS). Data were analyzed by repeated measures ANOVA followed by the Bonferroni test (p <0.05). Area under the curve (AUC) was calculated for saliva data. Result: No significant difference was observed between the groups regarding the retention of F in saliva. However, the largest area under the curve values in saliva were found for groups G3 and G4. The highest median values of F-biofilm were found in G3 for 1h and 12h collection times. Conclusion: The toothpaste containing Refix (RDCA) technology presented the most promising results for fluoride retention in oral exposure biomarkers.

Condition or disease	Intervention/treatment	Phase
Fluoride Biomarkers in the Oral Mouth After Brushing Teeth With the Experimental Dentifrice; Bioavailability of Fluoride in the Oral Mouth	Other: DENTIFRICE	Not Applicable

Detailed Description:

A randomized, duple-blind crossover clinical trial study was performed to evaluate the bioavailability of intraoral fluoride in biomarkers of exposure (biofilm and saliva) after the use of dentifrice with experimental fluoride for one week, with wash-out periods between them. The biofilm was collected 1 hour (h) and 12h after toothbrushing, and saliva was collected 1h (T1, T15, T30, T45, T60 min) and 12h. The data was obtained by potentiometry (ion selective electrode) for fluoride in these samples.

Study population The sample size was determined by sample calculation [25], according to previous studies [26], α = 5%, β = 10%, and a dropout ratio of 10%. Eighteen individuals with an average of 26 years old, including both males and females, participated in this study. The eligibility criteria were people over 18 years old, without systemic commitment and living in the city of João Pessoa-Paraíba, without water fluoridation (< 0.1 μg/mL F). Individuals were excluded if they used drugs that interfere with biofilm formation and salivary flow or fluoride products (> 5000 ppm) in the last 4 weeks, used orthodontic appliances, or had cavity lesions, periodontal disease, and/or tooth sensitivity.

Experimental Dentifrices The participants were allocated randomly to use the following experimental dentifrices according to table 1. They were coded by an independent investigator not involved in the trial. A simple randomization was performed taking into account a cross design. The unit of randomization was "dentifrice", so all dentifrices had the same chance of being selected. The design of the study was created for each participant and for each new one another draw was made.

Clinical Stage First, the participants were submitted to dental prophylaxis and scraping to remove all biofilm and dental calculus. They used a placebo, dentifrice without fluoride, for 7 days. Then, the Whitford protocol was followed [16]. Briefly, the subjects were instructed to brush their teeth three times/day for 1 min (transversal technique) and also to rinse their mouths after brushing with 10 mL of water. On the seventh day, the subjects were instructed to brush only the occlusal surfaces and do not use dental floss, to allow biofilm accumulation. After going to bed, they abstained from eating or drinking anything except water and did not brush their teeth. The next morning, after 12 hours of last brushing, and fasting, the first samples of saliva and biofilm (upper and lower right hemi-arch) were collected. Then, the volunteers brushed the occlusal surfaces for 1 min. Soon after, saliva samples were collected in the following times: t1, t15, t30, t45, and t60 minutes. Biofilme samples (left side) were collected later (1 hour after brushing). Resting saliva was collected for 5 minutes. The biofilm was collected from all tooth surfaces, in both buccal and lingual areas, using a 3S hollenback spatula, from which the samples were immediately transferred to an eppendorff tube, centrifuged and subsequently dried at 90°C for two hours and then weighed. The saliva samples were centrifuged at 6,000 rpm for 10 minutes in order to separate the saliva debris.

Determination of the concentration of fluoride The samples were analyzed by the hexamethyldisiloxane (HMDS) facilitated diffusion method of Taves [20] modified by Whitford [21]. The analyzes were performed with a fluoride specific electrode (model 9409; Orion Research) and a potentiometer (model EA 940; Orion Research, Cambridge, MA, USA) (Model 720 A Orion). Fluoride standards (1-100 nM) were used to prepare calibration curves.

Statistical analysis The data were analyzed using descriptive and inferential statistics, using the statistical program SPSS - v. 21.0 and software Graphpad. The Shapiro-Wilk test was applied to test the normality of the in vivo study data (n <50). Nonparametric tests were performed. The area under the curve (AUC) was calculated by taking baseline values (12 h after the last brush) up to 60 min after the last brush to indicate the effectiveness of F retention in saliva over time. For the purpose of comparing the concentration of F in saliva and biofilm between the groups, the ANOVA test of repeated measures was performed followed by the Bonferroni post-test. The relationship between the concentrations of biofilm and salivary fluoride was determined using Spearman's correlation coefficient. This study assumed a significance level of 5% (p <0.05).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Crossover study testing 4 dental gel for brushing teeth. the brushing period of use :7 days, 3 times daily with wahs-out periods of one week.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: the products are coded with different color in the label.
• Primary Purpose: Prevention
• Official Title: Dentifrice With Innovative Remineralizing Technology: a Randomized Clinical Study
• Actual Study Start Date: February 3, 2020
• Estimated Primary Completion Date: April 12, 2021
• Estimated Study Completion Date: September 12, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: G0 - placebo; Dental gel without fluoride in the composition	Other: DENTIFRICE; GEL -DENTIFRICE FOR BRUSHING TEETH; Other Name: TOOTHPASTE
Sham Comparator: G1: Daily Regenerator Dentalclean Neutro (RDCN); 1450 ppm F- of sodium fluoride and tetrasodium pyrophosphate (Refix technology). NEUTRAL pH	Other: DENTIFRICE; GEL -DENTIFRICE FOR BRUSHING TEETH; Other Name: TOOTHPASTE
Active Comparator: G2: Sensodyne Repair & Protect (SRP); 1426 ppm of sodium fluoride and calcium sodium phosphosilicate 5% (NOVAMIN technology).	Other: DENTIFRICE; GEL -DENTIFRICE FOR BRUSHING TEETH; Other Name: TOOTHPASTE
Experimental: G3: Daily Regenerator Dentalclean Acid (RDCA); 1450 ppm F- of sodium fluoride and tetrasodium pyrophosphate (Refix technology). ACIDIC FORMULA	Other: DENTIFRICE; GEL -DENTIFRICE FOR BRUSHING TEETH; Other Name: TOOTHPASTE
Active Comparator: G4: Colgate Total Daily Repair (CTDR); 1450 ppm F- of as sodium fluoride, 0.30% triclosan, arginine, tetrasodium pyrophosphate.	Other: DENTIFRICE; GEL -DENTIFRICE FOR BRUSHING TEETH; Other Name: TOOTHPASTE

Outcome Measures

Primary Outcome Measures :

1. FLUORIDE IN SALIVA [ Time Frame: 12 hours ]
   Concentration of fluoride in saliva after brushing teeth
2. FLUORIDE IN DENTAL PLAQUE [ Time Frame: 12 hours ]
   Concentration of fluoride in dental biofilm after brushing teeth

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• The eligibility criteria were people over 18 years old, without systemic commitment and living in the city of João Pessoa-Paraíba, without water fluoridation (< 0.1 μg/mL F).

Exclusion Criteria:

• Individuals were excluded if they used drugs that interfere with biofilm formation and salivary flow or fluoride products (> 5000 ppm) in the last 4 weeks, used orthodontic appliances, or had cavity lesions, periodontal disease, and/or tooth sensitivity.

Contacts and Locations

Locations

Brazil

Federal University of Paraíba; Recruiting

João Pessoa, Paraíba, Brazil

Contact: Fábio C Sampaio, Doctor +55 83 32167795 fcsampa@gmail.com

Sponsors and Collaborators

Federal University of Paraíba

More Information

• Responsible Party: Fabio Correia Sampaio, Professor, Federal University of Paraíba
• ClinicalTrials.gov Identifier: NCT04730908
• Other Study ID Numbers: REFIX-UFPB
• First Posted: January 29, 2021
• Last Update Posted: January 29, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No