Impact of a Triclosan-containing Toothpaste During the Progression of Experimental Peri-implant Mucositis
Condition: Biological Markers; Dental Implants; Cytokines; Triclosan; Toothpastes; Peri-Implantitis; Microbiology
MeSH terms: Mucositis; Peri-Implantitis
Study type: Interventional

Summary: 
      The aim of this study was to evaluate the influence of a triclosan-containing toothpaste in
      the profile of osteo-immunoinflammatory mediators in the peri-implant crevicular fluid (PICF)
      and in the clinical parameters during the progression of experimental peri-implant mucositis.
    

Detailed description: 
      Study design This investigation was designed as double-blind, randomized, crossover study to
      evaluate the influence of a triclosan-containing toothpaste in the profile of
      osteo-immunoinflammatory mediators in the PICF and in the clinical parameters during the
      progression of experimental peri-implant mucositis. This study was approved by the ethics
      committee of Paulista University (Protocol 97.117).

      Population screening Patient recruitment started in June 2013 and was completed by the end of
      May 2014. The clinical procedures and evaluations were carried out between August 2013 and
      June 2014. Data entry and statistical analyses were performed in January 2015. All the
      patients in the study were recruited from the patients referred to Paulista University.

      All eligible individuals were thoroughly informed of the nature, potential risks and benefits
      of their participation in the study, and they each signed an informed consent document.

      Experimental groups During an experimental 3-week period of undisturbed plaque accumulation
      in the implants, patients were randomly assigned to two groups, according to chemical plaque
      control (three times per day): Triclosan (n=11): triclosan/copolymer/fluoride toothpaste or
      Placebo (n=11): fluoride toothpaste. Undisturbed plaque accumulation was achieved only in the
      nearby of dental implants by using an individual silicone tray involving the implant and
      adjacent teeth covering 2-3mm of peri-implant mucosa. The same silicone tray was filled by
      the respective toothpaste, according to the experimental group, during this period. Following
      3 weeks, a professional prophylaxis was performed and a wash-out period of 30 days was
      established. Then, a second experimental 3-week period of undisturbed plaque accumulation in
      the implants was established and the experimental groups were exchanged. After that, a new
      professional prophylaxis was performed. All evaluations (clinical and immunoenzimatic assays)
      were performed at baseline, 3, 7, 14 and 21 days of each period of experimental mucositis
      induction.

      The number of patients included in the present study was based on previous crossover
      investigations that found differences in the clinical parameters and crevicular fluid levels
      of osteo-immunoinflammatory markers in different clinical status.

      Clinical examination The same examiner, who was blinded to the groups, performed all
      measurements of clinical assessment. To perform the intra-examiner calibration, 15 non-study
      individuals presenting dental implants were selected. The examiner measured the PD of all
      patients twice within 24 hours. The examiner was judged to be reproducible after fulfilling
      the pre-determined success criteria (the percentage of agreement within ± 1 mm between
      repeated measurements had to be at least 90%). The intra-class correlation was calculated as
      92% reproducibility.

      An individual stent was prepared to standardize the location of periodontal probe (North
      Carolina - Hu-Friedy, Chicago, IL, USA) to evaluate the following parameters at four sites of
      the experimental dental implants at baseline, 3, 7, 14, 21 days follow-ups: 1) plaque index
      (PI/%): scored using a dichotomous plaque index along the mucosal margin around implants, 2)
      bleeding index (BI/%): scored using dichotomous index of mucosal marginal bleeding around
      implants, 3) Position of the peri-implant margin (PPM/mm), which was the distance from the
      stent to the peri-implant margin; 4) Relative clinical attachment level (RCAL/mm), which was
      the distance from the stent to the bottom of the peri-implant pocket; and 5) Peri-implant
      probing depth (PD/mm), calculated by deducting PPM from RCAL. The full mouth plaque scores
      (FMPS) and bleeding scores (FMBS) were calculated before the beginning of each period of
      experimental mucositis induction.

      Osteo-immunoinflammatory profile assessment Peri-implant crevicular fluid was collected from
      dental implant sites by the same examiner. The area was isolated, dried and fluid was
      collected at two sites of the experimental dental implants (vestibular and lingual) by
      placing filter paper strips (Periopaper, Oraflow, Plainview, NY, USA) into the sulcus until
      the clinician perceived a slight resistance, and then leaving in place for 15 s. The fluid
      volume was measured with a calibrated device (Periotron 8000, Oraflow, Plainview, NY, USA).
      The strips were placed into sterile tubes containing 400 μL of phosphate-buffered saline
      (PBS) with 0.05% Tween-20. Peri-implant crevicular fluid samples were immediately stored at
      -20 °C.

      Levels of interferon (INF), interleukin (IL)-4, IL-17, IL-1β, IL-10, IL-6, IL-23, tumor
      necrosis factor (TNF)-α (Human Th17 HTH17MAG-14K, Millipore Corporation, Billerica, MA, USA),
      osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN) (Human Bone HBNMAG-51K, Millipore
      Corporation, Billerica, MA, USA), matrix metalloproteinase (MMP)-2, MMP-9 (Human MMP Panel 2
      HMMP2MAG-55K, Millipore Corporation, Billerica, MA, USA), transforming growth factor (TGF)-β
      (Multi-species TGFβ TGFBMAG-64K, Millipore Corporation, Billerica, MA, USA) and crosslinked
      telopeptide of type I collagen (ICTP) (Uscn Life Science Inc. Wuhan, Hubei, PRC) in the
      peri-implant fluid were determined using commercially available kits. Assays were carried out
      according to the manufacturer's recommendations using the MAGpix™ instrument (MiraiBio,
      Alameda, CA, USA). The samples were individually analyzed, and concentrations were estimated
      from the standard curve using a five-parameter polynomial equation using Xponent® software
      (Millipore, Corporation, Billerica, MA, USA). The mean concentration of each mediator was
      calculated using the individual as a statistical unit and expressed as pg/ml.

      Data analysis All analyses were performed using SAS program release 9.1 (Cary, NC, USA). Data
      were firstly examined for normality using the Kolmogorov-Smirnov test, and the data that
      achieved normality were analysed using parametric methods. The percentages of experimental
      sites with visible plaque accumulation, BI and the PD means were computed for each implant
      selected for peri-implant fluid sampling. Subsequently, clinical parameters and the local
      levels of osteo-immunoinflammatory mediators were averaged into Placebo and Triclosan groups.
      The differences in FMPS and FMBS - measured before the beginning of each period of
      experimental mucositis induction.- between both groups were compared using the Wilcoxon test.
      For the other clinical parameters (PI, BI, PPM, RCAL and PD), ANOVA/Tukey test was used to
      detect differences between groups and periods. Concentrations of osteo-immunoinflammatory
      markers between groups and among follow-ups were compared using the Wilcoxon and Friedman
      test, respectively. An experimental level of significance was determined at 5% for all
      statistical analyses.
    

Intervention name(s): Placebo toothpaste; triclosan/copolymer/fluoride toothpaste
Intervention type(s): Other; Other
Intervention description(s): During an experimental 3-week period of undisturbed mechanical plaque accumulation in the implants, implants randomly assigned to Placebo group will be submitted to a chemical plaque control (three times per day) using a Triclosan toothpaste.; During an experimental 3-week period of undisturbed mechanical plaque accumulation in the implants, implants randomly assigned to triclosan/copolymer/fluoride group will be submitted to a chemical plaque control (three times per day) using a triclosan/copolymer/fluoride toothpaste.
Intervention MeSH terms: Triclosan; Fluorides
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This investigation was designed as double-blind, randomized, crossover study
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment