Fluoride Controlled-release System for Initial Lesions of Caries
Condition: White Spot Lesion
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      OBJECTIVE: To evaluate in vivo the efficacy of fluoride-containing dentifrice incorporated in
      a controlled-release system (F-CSL, patent pending) in the remineralization of white spot
      lesions of caries in caries-active individuals. METHODS: A double-blind randomized clinical
      trial to evaluate the bioavailability of intraoral fluoride in biomarkers of exposure
      (biofilm and saliva) after the use of experimental toothpaste in the control of dental
      caries. The study will last three months. The participants of the study will be divided into
      three groups according to the dentifrice used. The sample will be selected randomly and
      composed of children and adolescents who seek the service of cariology of the UFPB. There
      will be participants of both sexes, preferably of the metropolitan region of João Pessoa in
      order to guarantee the low fluorine exposure by the water of supply. Intrabucal photographs
      will be obtained. Samples of saliva will be collected after 3 hours of the last meal. The
      benefits will be achieved by obtaining the reduction of the white spot area (mm2) plus the
      fact that all the children will be examined and will receive information on the treatment
      needs and forwading for the same.
    

Detailed description: 
      Study Design:A randomized, triple-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 mouthwash with experimental fluoride for one week, with wash-out
      periods between them. The biofilm was collected 1 hour (h) and 12h after toothbrushing and
      the use of mouthwash, and saliva was collected 1h (T1 - T60 min) and 12h. The data was
      obtained by potentiometry (ion selective electrode) for fluoride in these samples. The pilot
      test was performed with three participants before the study begins.

      Experimental mouthwashes:The participants were allocated randomly to use the following
      experimental mouthwashes: P - placebo (without F); 100% sodium fluoride (NaF) (225 ppm) -
      positive control; 50% nanoencapsulated fluoride (225 ppm, 50% free NaF + 50% nanoF); and 100%
      nanoF (225 ppm) (Savoy SA - São Paulo, Brazil). All mouthwashes were packed in similar
      containers and had the same color and flavor. 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 "mouthwash", so all mouthwashes 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 mouthwash for 7 days. Then, the
      Whitford protocol was followed [17]. Briefly, the subjects were instructed to rinse 10 ml of
      the mouthwash 2 times / day (morning and evening) for 1 min after toothbrushing (a non-F
      dentifrice was used throughout the study). On the seventh day, the subjects were instructed
      to brush only the occlusal surfaces, rinse the mouthwash 2 times and do not use dental floss,
      to allow biofilm accumulation. After going to bed, they abstained from eating or drinking
      anything except water, did not brush their teeth or use the mouthwash. The next morning,
      after 12 hours of last brushing and mouthwash, and fasting, the first samples of stimulated
      saliva and biofilm (upper and lower right hemi-arch) were collected. Then, the volunteers
      brushed the occlusal surfaces and rinsed 10 mL of the mouthwash for 1 min. Soon after, saliva
      samples were collected in the following times: t1, t5, t10, t15, t20, t30, t45 and t60
      minutes. Later, 1 hour after the mouthwash, the biofilm samples (left side) were collected.

      The stimulated saliva (chewing on a silicone) was collected for 2 min, posteriorly the saliva
      samples were centrifuged at 6,000 rpm for 10 minutes in order to separate the saliva debris.
      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, subsequently dried at 60 °C for 4 h and then weighed.

      Determination of the concentration of fluoride:The samples were analyzed by the
      hexamethyldisiloxane (HMDS) facilitated diffusion method of Taves [21] modified by Whitford
      [22]. 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:Statistical analysis were performed in software R considering α = 0.05.
      The Shapiro-Wilk and Kolmogorov Smirnov tests were applied to evaluate the normality of the
      data. The comparisons of F concentration in saliva and biofilm between groups were performed
      by repeated measures ANOVA after the Bonferroni test. The AUC measure (area below the curve)
      was calculated to indicate the efficacy of F retention in the saliva over the long term by
      taking the F concentration values in the time interval from 12h to 60 min after the last
      rinse. The relationship between fluoride concentrations in biofilm and saliva was determined
      using Spearman's correlation coefficient. The data was calculated on Graph Pad Prism (version
      6) and Statistical Package (SPSS) version 23.
    

Intervention name(s): Mouthwash Product
Intervention type(s): Drug
Intervention description(s): The participants were requested to rinse 10 ml of the mouthwash 2 times / day (morning and evening) for 1 min after toothbrushing (a non-F dentifrice was used throughout the study).
Other intervention name(s): nano fluoride
Intervention MeSH terms: Fluorides
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: A randomized, triple-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 mouthwash with experimental fluoride for one week, with wash-out periods between them
Masking: Single (Care Provider)
Primary purpose: Treatment
Keywords: fluorine; dental plaque; Toothbrushing