<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/NCT01706874</url>
  </required_header>
  <id_info>
    <org_study_id>2011- AO1271 - 40</org_study_id>
    <nct_id>NCT01706874</nct_id>
  </id_info>
  <brief_title>Effect Assessment of Periodontal Prophylaxis on Rheumatoid Arthritis Activity.</brief_title>
  <acronym>BHYRRA</acronym>
  <official_title>Assessment of the Effect of an Intervention (Periodontal Scaling + Mouthwash + Toothpaste) to Reduce the Load on Oral Bacterial Activity of Rheumatoid Arthritis: a Randomized Trial Nested in the Cohort ESPOIR</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Société Française de Parodontologie et d'Implantologie Orale (SFPIO)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the impact of an intervention (scaled every 06 months&#xD;
      associated with the use of mouthwash with essential oils (toothpaste and Listerine® 2 times /&#xD;
      day containing polymer Triclosan (Colgate Total®)) on the activity of rheumatoid arthritis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction: Several epidemiological studies have suggested that a link between periodontal&#xD;
      disease and rheumatoid arthritis. In cohorts, the risk of development of rheumatoid arthritis&#xD;
      is increased in subjects with periodontal disease. The main bacterium implicated in chronic&#xD;
      periodontal disease is Porphyromas gingivalis, a commensal microorganism of the mouth. P.&#xD;
      gingivalis is the only microorganism with a deiminase capable of transforming arginine into&#xD;
      citrulline, and is suspected of to play a major role in the production of anti-citrulline&#xD;
      antibodies, the principal diagnostic marker of rheumatoid arthritis.&#xD;
&#xD;
      Hypotheses: The regular professional and individual plaque control in patients with&#xD;
      rheumatoid arthritis (standard of care) - i.e. decreasing oral bacterial load, including P.&#xD;
      gingivalis - reduces the activity of rheumatoid arthritis Principal objective: To assess the&#xD;
      impact of professional periodontal scaling every 6 months combined with the individual plaque&#xD;
      control, i.e. toothbrushing plus the use of mouthrinses on rheumatoid arthritis activity.&#xD;
&#xD;
      Methodology: The trial design is innovative and based on random selection of a sample of&#xD;
      patients in an observational cohort of patients as described in the recent publication&#xD;
      &quot;Cohort Multiple Randomised Controlled Trials Design&quot; (Ref.: BMJ 2010; 340: c1066). A&#xD;
      randomly selected sample of eligible patients from the cohort will be asked to take part in&#xD;
      the study. Changes in the randomised sample will be compared to those of other potentially&#xD;
      eligible patients from the cohort. The cohort used will be the ESPOIR cohort, a cohort&#xD;
      including 813 patients who initially presented with early undifferentiated polyarthritis that&#xD;
      developed into rheumatoid arthritis with anti-citrulline antibodies in approximately 40 to&#xD;
      50% of cases.&#xD;
&#xD;
      Procedures studied: Periodontal scaling every 6 months and twice daily use of a mouthwash&#xD;
      containing essential oils (Listerine®) plus a triclosan/copolymer toothpaste (Colgate&#xD;
      Total®).&#xD;
&#xD;
      Sample size calculation: The principal assessment criterion is DAS variations at 1 year. The&#xD;
      expected statistical power is 80% (the type I risk being set at 5%) and the standard&#xD;
      deviation common to the two samples for DAS variation is evaluated at 1.5. With these&#xD;
      hypotheses, the inclusion of 100 patients in the study group and 100 patients in the control&#xD;
      group will produce an effect size of 0.40 (i.e. a difference in DAS between the two groups&#xD;
      equal to 0.6).&#xD;
&#xD;
      Statistical analysis: A linear, mixed-effects model will be used to compare DAS variations&#xD;
      between the two groups. In addition, the Mixed Model for Repeated Measurements (MMRM) based&#xD;
      on a linear mixed model will include two other random effects, i.e.: the centre effect and&#xD;
      the centre*treatment interaction effect, which will be used to measure heterogeneity between&#xD;
      the centres and heterogeneity of the effect of the procedure. Finally, propensity scores with&#xD;
      adjustment by weighting will be used to take into account any potential imbalances between&#xD;
      the two study arms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 20, 2012</start_date>
  <completion_date type="Actual">July 26, 2017</completion_date>
  <primary_completion_date type="Actual">September 7, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Periodontal prophylaxis</measure>
    <time_frame>at 12 months</time_frame>
    <description>Assessment of the effect of an intervention : periodontal prophylaxis (periodontal scaling + mouthwash + toothpaste)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Bacterial identification</measure>
    <time_frame>at 12 months</time_frame>
    <description>Assessment of the effect of an intervention: Bacterial identification. A bacterial sampling at 4 deepest periodontal pockets will be carried.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Disease activity score (DAS) 28</measure>
    <time_frame>at 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of anti-citrulline and anti P. gingivalis antibodies</measure>
    <time_frame>at 12 months</time_frame>
    <description>Evaluate the impact of this intervention on the rate of anti-citrulline and anti P. gingivalis antibodies. A bacterial sampling at 4 deepest periodontal pockets will be carried.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">92</enrollment>
  <condition>Anti-CCP Positive Early Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Periodontal prophylaxis</arm_group_label>
    <description>Periodontal prophylaxis (standard of care) versus control in rheumatoid arthritis patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>Periodontal prophylaxis (standard of care) versus control in rheumatoid arthritis patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Periodontal prophylaxis</intervention_name>
    <description>Periodontal scaling (every 6 months) plus mouthrinses plus toothbrushing (twice daily). Removal of adherent plaque and calculus with ultrasonic instruments and hand instruments, such as periodontal scalers and curettes, and polishing of the teeth</description>
    <arm_group_label>Periodontal prophylaxis</arm_group_label>
    <other_name>Mouthrinse: Listerine®; toothpaste: Colgate Total®</other_name>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Biospecimen: gingival fluid&#xD;
&#xD;
      A first sampling will take place at T0 and the second at Month 12 (test end).&#xD;
&#xD;
      A bacterial sampling at 4 deepest periodontal pockets will be carried. It will quantify the 9&#xD;
      following bacteria:&#xD;
&#xD;
      Aggregatibacter actinomycetemcomitans Porphyromonas gingivalis Prevotella intermedia&#xD;
      Tannerella forsythensis Treponema denticola Peptostreptococcus micros Fusobacterium nucleatum&#xD;
      Eikenella corrodens Campylobacter rectus&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Population selected from the ESPOIR early arthritis Cohort&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with rheumatoid arthritis according to EULAR criteria / ACR 2010 under 10&#xD;
             years of evolution&#xD;
&#xD;
          -  Patients included in the ESPOIR cohort&#xD;
&#xD;
          -  Patients with DAS28 &gt; 3.2&#xD;
&#xD;
          -  Anti-CCP positive and negative&#xD;
&#xD;
          -  Age: 18 years old to 80 years&#xD;
&#xD;
          -  Affiliated to social security&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to participate in the study&#xD;
&#xD;
          -  DAS28 &lt; 3.2&#xD;
&#xD;
          -  Patient under guardianship&#xD;
&#xD;
          -  Participation in another protocol without agreement of the dentist&#xD;
&#xD;
          -  Not affiliated to social security&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xavier MARIETTE, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Paris-Sud University, AP-HP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Philippe BOUCHARD, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Paris Diderot University, AP-HP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Philippe RAVAUD, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Paris Descartes University, AP-HP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Rotschild - Service d'Odontologie</name>
      <address>
        <city>Paris</city>
        <zip>75571</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>September 14, 2012</study_first_submitted>
  <study_first_submitted_qc>October 12, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2012</study_first_posted>
  <last_update_submitted>July 31, 2017</last_update_submitted>
  <last_update_submitted_qc>July 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid arthritis</keyword>
  <keyword>P.gingivalis</keyword>
  <keyword>Periodontal disease</keyword>
  <keyword>Plaque control</keyword>
  <keyword>Prophylaxis</keyword>
  <keyword>Oral hygiene instruction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Listerine</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/NCT01706874
org study id: 2011- AO1271 - 40
nct id: NCT01706874
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to assess the impact of an intervention (scaled every 06 months
      associated with the use of mouthwash with essential oils (toothpaste and Listerine® 2 times /
      day containing polymer Triclosan (Colgate Total®)) on the activity of rheumatoid arthritis
Introduction: Several epidemiological studies have suggested that a link between periodontal
      disease and rheumatoid arthritis. In cohorts, the risk of development of rheumatoid arthritis
      is increased in subjects with periodontal disease. The main bacterium implicated in chronic
      periodontal disease is Porphyromas gingivalis, a commensal microorganism of the mouth. P.
      gingivalis is the only microorganism with a deiminase capable of transforming arginine into
      citrulline, and is suspected of to play a major role in the production of anti-citrulline
      antibodies, the principal diagnostic marker of rheumatoid arthritis.

      Hypotheses: The regular professional and individual plaque control in patients with
      rheumatoid arthritis (standard of care) - i.e. decreasing oral bacterial load, including P.
      gingivalis - reduces the activity of rheumatoid arthritis Principal objective: To assess the
      impact of professional periodontal scaling every 6 months combined with the individual plaque
      control, i.e. toothbrushing plus the use of mouthrinses on rheumatoid arthritis activity.

      Methodology: The trial design is innovative and based on random selection of a sample of
      patients in an observational cohort of patients as described in the recent publication
      "Cohort Multiple Randomised Controlled Trials Design" (Ref.: BMJ 2010; 340: c1066). A
      randomly selected sample of eligible patients from the cohort will be asked to take part in
      the study. Changes in the randomised sample will be compared to those of other potentially
      eligible patients from the cohort. The cohort used will be the ESPOIR cohort, a cohort
      including 813 patients who initially presented with early undifferentiated polyarthritis that
      developed into rheumatoid arthritis with anti-citrulline antibodies in approximately 40 to
      50% of cases.

      Procedures studied: Periodontal scaling every 6 months and twice daily use of a mouthwash
      containing essential oils (Listerine®) plus a triclosan/copolymer toothpaste (Colgate
      Total®).

      Sample size calculation: The principal assessment criterion is DAS variations at 1 year. The
      expected statistical power is 80% (the type I risk being set at 5%) and the standard
      deviation common to the two samples for DAS variation is evaluated at 1.5. With these
      hypotheses, the inclusion of 100 patients in the study group and 100 patients in the control
      group will produce an effect size of 0.40 (i.e. a difference in DAS between the two groups
      equal to 0.6).

      Statistical analysis: A linear, mixed-effects model will be used to compare DAS variations
      between the two groups. In addition, the Mixed Model for Repeated Measurements (MMRM) based
      on a linear mixed model will include two other random effects, i.e.: the centre effect and
      the centre*treatment interaction effect, which will be used to measure heterogeneity between
      the centres and heterogeneity of the effect of the procedure. Finally, propensity scores with
      adjustment by weighting will be used to take into account any potential imbalances between
      the two study arms.
observational model: Case-Control
time perspective: Prospective
measure: Periodontal prophylaxis
time frame: at 12 months
description: Assessment of the effect of an intervention : periodontal prophylaxis (periodontal scaling + mouthwash + toothpaste)
measure: Bacterial identification
time frame: at 12 months
description: Assessment of the effect of an intervention: Bacterial identification. A bacterial sampling at 4 deepest periodontal pockets will be carried.
measure: Disease activity score (DAS) 28
time frame: at 12 months
measure: Rate of anti-citrulline and anti P. gingivalis antibodies
time frame: at 12 months
description: Evaluate the impact of this intervention on the rate of anti-citrulline and anti P. gingivalis antibodies. A bacterial sampling at 4 deepest periodontal pockets will be carried.
arm group label: Periodontal prophylaxis
description: Periodontal prophylaxis (standard of care) versus control in rheumatoid arthritis patients.
arm group label: Control
description: Periodontal prophylaxis (standard of care) versus control in rheumatoid arthritis patients
intervention type: Other
intervention name: Periodontal prophylaxis
description: Periodontal scaling (every 6 months) plus mouthrinses plus toothbrushing (twice daily). Removal of adherent plaque and calculus with ultrasonic instruments and hand instruments, such as periodontal scalers and curettes, and polishing of the teeth
arm group label: Periodontal prophylaxis
other name: Mouthrinse: Listerine®; toothpaste: Colgate Total®
Biospecimen: gingival fluid

      A first sampling will take place at T0 and the second at Month 12 (test end).

      A bacterial sampling at 4 deepest periodontal pockets will be carried. It will quantify the 9
      following bacteria:

      Aggregatibacter actinomycetemcomitans Porphyromonas gingivalis Prevotella intermedia
      Tannerella forsythensis Treponema denticola Peptostreptococcus micros Fusobacterium nucleatum
      Eikenella corrodens Campylobacter rectus
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Xavier MARIETTE, MD, PhD
role: Study Chair
affiliation: Paris-Sud University, AP-HP
last name: Philippe BOUCHARD, MD, PhD
role: Principal Investigator
affiliation: Paris Diderot University, AP-HP
last name: Philippe RAVAUD, MD, PhD
role: Principal Investigator
affiliation: Paris Descartes University, AP-HP
facility: 
country: France
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Listerine
sharing ipd: No