<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03241407</url>
  </required_header>
  <id_info>
    <org_study_id>Triclosan Mucositis Smoking</org_study_id>
    <nct_id>NCT03241407</nct_id>
  </id_info>
  <brief_title>Triclosan Toothpaste as a Preventive Strategy of Mucositis in Smokers</brief_title>
  <official_title>Effect of a Triclosan-containing Toothpaste as a Preventive Strategy of Peri-implant Experimental Mucositis in Cigarette Smokers: Clinical and Osteo-immunoinflammatory Response in a Randomized Crossover Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Paulista University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Paulista University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial was to determine the effect of a triclosan-containing toothpaste in&#xD;
      the clinical parameters and in the profile of osteo-immunoinflammatory mediators in the&#xD;
      peri-implant crevicular fluid (PICF) as a preventive therapy of peri-implant experimental&#xD;
      mucositis in cigarette smokers&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was designed as double-blind, randomized, crossover study to evaluate the&#xD;
      influence of a triclosan-containing toothpaste in the profile of osteo-immunoinflammatory&#xD;
      mediators in the PICF of smoker individuals and in the clinical measurements during the&#xD;
      progression of experimental peri-implant mucositis. This investigation was approved by the&#xD;
      ethics committee of Paulista University . Patient recruitment started in July 2013 and was&#xD;
      completed by the end of September 2014. Clinical procedures and evaluations were carried out&#xD;
      between September 2013 and November 2014. Data entry and statistical analyses were performed&#xD;
      in April 2015. All the patients in the study were recruited from the patients referred to&#xD;
      Paulista University. Patients were thoroughly informed of the nature, potential risks and&#xD;
      benefits of their participation in the study, and they each signed an informed consent&#xD;
      document. During this 3-week period, participants were randomly assigned to two groups by a&#xD;
      computer-generated list: Triclosan (n=13): triclosan/copolymer/fluoride toothpaste or Placebo&#xD;
      (n=13): fluoride toothpaste, by filling the individual silicone stent with the respective&#xD;
      toothpaste, according to the experimental group, and allowing it to come into contact with&#xD;
      the implant area for 2 min, three times per day. Conventional tooth brushing was performed in&#xD;
      the non-stent areas.&#xD;
&#xD;
      After 3 weeks, a professional prophylaxis was performed and a wash-out period of 30 days was&#xD;
      established. All patients restarted their optimal mechanical plaque control practices to&#xD;
      reach pre-experimental levels of oral cleanliness and gingival/mucosal health. Then, a second&#xD;
      experimental 3-week period of undisturbed plaque accumulation around the implants was&#xD;
      established and the experimental groups were exchanged. After that, a new professional&#xD;
      prophylaxis was performed. Patients were blinded to the therapies.All evaluations (clinical&#xD;
      and immunoenzimatic) were performed at baseline, 3, 7, 14 and 21 days of each period of&#xD;
      experimental mucositis induction. Levels of osteo-immunoinflammatory mediators were&#xD;
      considered primary outcome variable. The number of patients included was based on previous&#xD;
      crossover investigations that found differences in the crevicular fluid levels of&#xD;
      osteo-immunoinflammatory markers in different clinical status. The same examiner (SPP), who&#xD;
      was blinded to the groups, performed all clinical measurements. To perform the intra-examiner&#xD;
      calibration, 15 non-study individuals presenting dental implants were selected. The examiner&#xD;
      measured the PD of all individuals twice within 24 hours. The intra-class correlation was&#xD;
      calculated as 95% reproducibility.&#xD;
&#xD;
      Individual stents were prepared to standardize the location of periodontal probe in order to&#xD;
      evaluate the following parameters at four sites of the experimental dental implants at&#xD;
      baseline, 3, 7, 14, 21 days follow-ups: 1) plaque index (PI/%): dichotomous plaque index&#xD;
      along the mucosal margin around implants, 2) Bleeding on probing (BOP,%):dichotomous index of&#xD;
      bleeding during probing around implants, 3) Position of the peri-implant margin (PPM/mm):&#xD;
      distance from the stent to the peri-implant margin; 4) Relative clinical attachment level&#xD;
      (RCAL/mm): distance from the stent to the bottom of the peri-implant pocket; and 5)&#xD;
      Peri-implant Probing depth (PD,mm): calculated by deducting PPM from RCAL.&#xD;
&#xD;
      Levels of interferon, interleukin (IL)-17, IL-1β, IL-10, IL-6, IL-8, tumor necrosis factor&#xD;
      (TNF)-α , osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN) , matrix&#xD;
      metalloproteinase (MMP)-2, MMP-9 , transforming growth factor (TGF)-β , soluble receptor&#xD;
      activator of nuclear factor ligand (RANKL) and crosslinked telopeptide of type I collagen&#xD;
      (ICTP) in the PICF were determined using the MAGpix™ instrument and Xponent® software . The&#xD;
      mean concentration of each mediator was calculated using the individual as a statistical unit&#xD;
      and expressed as pg/ml.&#xD;
&#xD;
      All analyses were completed using SAS program release 9.1 . Data were examined for normality&#xD;
      using the Kolmogorov-Smirnov test, and those that achieved normality were analysed using&#xD;
      parametric methods. FMPS and FMBS measured before the beginning of each period of&#xD;
      experimental mucositis in both groups were compared using the Wilcoxon test. For the other&#xD;
      clinical parameters (PI, BoP, PPM, RCAL and PD), ANOVA two way/Tukey test was used to detect&#xD;
      differences between groups and periods. Levels of osteo-immunoinflammatory markers between&#xD;
      groups and among follow-ups were compared using the Wilcoxon and Friedman test, respectively.&#xD;
      An experimental level of significance was determined at 5%.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2013</start_date>
  <completion_date type="Actual">April 30, 2015</completion_date>
  <primary_completion_date type="Actual">September 1, 2013</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>This investigation was designed as double-blind, randomized, crossover study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Osteo-immunoinflammatory mediators</measure>
    <time_frame>21 days</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>bleeding index</measure>
    <time_frame>21 days</time_frame>
    <description>scored using dichotomous index of mucosal marginal bleeding around implants</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>plaque index</measure>
    <time_frame>21 days</time_frame>
    <description>scored using a dichotomous plaque index along the mucosal margin around implants</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Position of the peri-implant margin</measure>
    <time_frame>21 days</time_frame>
    <description>distance from the stent to the bottom of the peri-implant pocket</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peri-implant probing depth</measure>
    <time_frame>21 days</time_frame>
    <description>calculated by deducting PPM from RCAL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relative clinical attachment level</measure>
    <time_frame>21 days</time_frame>
    <description>which was the distance from the stent to the bottom of the peri-implant pocket;</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Dental Implants</condition>
  <condition>Cigarette Smoking</condition>
  <arm_group>
    <arm_group_label>Placebo toothpaste</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Fluoride toothpaste will be used by filling the individual silicone stent allowing it to come into contact with the implant area for 2 min.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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>triclosan/copolymer/fluoride toothpaste</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>triclosan/copolymer/fluoride toothpaste will be used by filling the individual silicone stent allowing it to come into contact with the implant area for 2 min. 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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo toothpaste</intervention_name>
    <description>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 placebo toothpaste.</description>
    <arm_group_label>Placebo toothpaste</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>triclosan/copolymer/fluoride toothpaste</intervention_name>
    <description>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.</description>
    <arm_group_label>triclosan/copolymer/fluoride toothpaste</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  30 years old or more&#xD;
&#xD;
          -  Patients should be smokers (more than 10 cigarettes/day, for at least 2 years),&#xD;
&#xD;
          -  present at least a 2-stage unitary screwed implant-supported single-unit crown in the&#xD;
             molar or pre-molar region implant connection should be external hexagonal and the&#xD;
             implants should be in function at least 12 months&#xD;
&#xD;
          -  width of keratinized tissue &gt; 2mm around implants&#xD;
&#xD;
          -  The peri-implant tissue should be healthy [probing depth (PD) &lt;4mm with no bleeding on&#xD;
             probing (BoP) and no evidence of radiographic bone loss beyond bone remodeling (AAP&#xD;
             2013).&#xD;
&#xD;
          -  Patients should be periodontally healthy and present full mouth plaque scores and&#xD;
             bleeding score &lt; 20%.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  lactation&#xD;
&#xD;
          -  systemic conditions r that could affect the progression of peri-implant diseases and&#xD;
             bone metabolism (e.g., immunologic disorders)&#xD;
&#xD;
          -  use of long-term administration of anti-inflammatory and immunosuppressive medications&#xD;
             antibiotic therapies in the previous 6 months&#xD;
&#xD;
          -  individuals that required bone grafts before or alongside the implant surgery history&#xD;
             of previous regenerative procedures in the area treated with implant therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>School of Dentistry - Paulista University UNIP</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>052</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>August 2, 2017</last_update_submitted>
  <last_update_submitted_qc>August 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Paulista University</investigator_affiliation>
    <investigator_full_name>Fernanda Vieira Ribeiro</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucositis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triclosan</mesh_term>
    <mesh_term>Fluorides</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03241407
org study id: Triclosan Mucositis Smoking
nct id: NCT03241407
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this trial was to determine the effect of a triclosan-containing toothpaste in
      the clinical parameters and in the profile of osteo-immunoinflammatory mediators in the
      peri-implant crevicular fluid (PICF) as a preventive therapy of peri-implant experimental
      mucositis in cigarette smokers
This study 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 of smoker individuals and in the clinical measurements during the
      progression of experimental peri-implant mucositis. This investigation was approved by the
      ethics committee of Paulista University . Patient recruitment started in July 2013 and was
      completed by the end of September 2014. Clinical procedures and evaluations were carried out
      between September 2013 and November 2014. Data entry and statistical analyses were performed
      in April 2015. All the patients in the study were recruited from the patients referred to
      Paulista University. Patients were thoroughly informed of the nature, potential risks and
      benefits of their participation in the study, and they each signed an informed consent
      document. During this 3-week period, participants were randomly assigned to two groups by a
      computer-generated list: Triclosan (n=13): triclosan/copolymer/fluoride toothpaste or Placebo
      (n=13): fluoride toothpaste, by filling the individual silicone stent with the respective
      toothpaste, according to the experimental group, and allowing it to come into contact with
      the implant area for 2 min, three times per day. Conventional tooth brushing was performed in
      the non-stent areas.

      After 3 weeks, a professional prophylaxis was performed and a wash-out period of 30 days was
      established. All patients restarted their optimal mechanical plaque control practices to
      reach pre-experimental levels of oral cleanliness and gingival/mucosal health. Then, a second
      experimental 3-week period of undisturbed plaque accumulation around the implants was
      established and the experimental groups were exchanged. After that, a new professional
      prophylaxis was performed. Patients were blinded to the therapies.All evaluations (clinical
      and immunoenzimatic) were performed at baseline, 3, 7, 14 and 21 days of each period of
      experimental mucositis induction. Levels of osteo-immunoinflammatory mediators were
      considered primary outcome variable. The number of patients included was based on previous
      crossover investigations that found differences in the crevicular fluid levels of
      osteo-immunoinflammatory markers in different clinical status. The same examiner (SPP), who
      was blinded to the groups, performed all clinical measurements. To perform the intra-examiner
      calibration, 15 non-study individuals presenting dental implants were selected. The examiner
      measured the PD of all individuals twice within 24 hours. The intra-class correlation was
      calculated as 95% reproducibility.

      Individual stents were prepared to standardize the location of periodontal probe in order 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/%): dichotomous plaque index
      along the mucosal margin around implants, 2) Bleeding on probing (BOP,%):dichotomous index of
      bleeding during probing around implants, 3) Position of the peri-implant margin (PPM/mm):
      distance from the stent to the peri-implant margin; 4) Relative clinical attachment level
      (RCAL/mm): 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.

      Levels of interferon, interleukin (IL)-17, IL-1β, IL-10, IL-6, IL-8, tumor necrosis factor
      (TNF)-α , osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN) , matrix
      metalloproteinase (MMP)-2, MMP-9 , transforming growth factor (TGF)-β , soluble receptor
      activator of nuclear factor ligand (RANKL) and crosslinked telopeptide of type I collagen
      (ICTP) in the PICF were determined using the MAGpix™ instrument and Xponent® software . The
      mean concentration of each mediator was calculated using the individual as a statistical unit
      and expressed as pg/ml.

      All analyses were completed using SAS program release 9.1 . Data were examined for normality
      using the Kolmogorov-Smirnov test, and those that achieved normality were analysed using
      parametric methods. FMPS and FMBS measured before the beginning of each period of
      experimental mucositis in both groups were compared using the Wilcoxon test. For the other
      clinical parameters (PI, BoP, PPM, RCAL and PD), ANOVA two way/Tukey test was used to detect
      differences between groups and periods. Levels 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%.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This investigation was designed as double-blind, randomized, crossover study
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Osteo-immunoinflammatory mediators
time frame: 21 days
description: 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.
measure: bleeding index
time frame: 21 days
description: scored using dichotomous index of mucosal marginal bleeding around implants
measure: plaque index
time frame: 21 days
description: scored using a dichotomous plaque index along the mucosal margin around implants
measure: Position of the peri-implant margin
time frame: 21 days
description: distance from the stent to the bottom of the peri-implant pocket
measure: Peri-implant probing depth
time frame: 21 days
description: calculated by deducting PPM from RCAL
measure: Relative clinical attachment level
time frame: 21 days
description: which was the distance from the stent to the bottom of the peri-implant pocket;
arm group label: Placebo toothpaste
arm group type: Placebo Comparator
description: Fluoride toothpaste will be used by filling the individual silicone stent allowing it to come into contact with the implant area for 2 min.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.
arm group label: triclosan/copolymer/fluoride toothpaste
arm group type: Experimental
description: triclosan/copolymer/fluoride toothpaste will be used by filling the individual silicone stent allowing it to come into contact with the implant area for 2 min. 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 type: Other
intervention name: Placebo toothpaste
description: 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 placebo toothpaste.
arm group label: Placebo toothpaste
intervention type: Other
intervention name: triclosan/copolymer/fluoride toothpaste
description: 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.
arm group label: triclosan/copolymer/fluoride toothpaste
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Paulista University
investigator full name: Fernanda Vieira Ribeiro
investigator title: Professor
mesh term: Mucositis
mesh term: Triclosan
mesh term: Fluorides
sharing ipd: No