Effect Assessment of Periodontal Prophylaxis on Rheumatoid Arthritis Activity. (BHYRRA)

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

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

Study Overview

• Status: Completed
• Conditions: Anti-CCP Positive Early Rheumatoid Arthritis
• Intervention / Treatment: Other: Periodontal prophylaxis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 92

Contacts and Locations

Study Locations

• France
  • Paris, France, 75571
    • Hôpital Rotschild - Service d'Odontologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Population selected from the ESPOIR early arthritis Cohort

Description

Inclusion Criteria:

• Patients with rheumatoid arthritis according to EULAR criteria / ACR 2010 under 10 years of evolution
• Patients included in the ESPOIR cohort
• Patients with DAS28 > 3.2
• Anti-CCP positive and negative
• Age: 18 years old to 80 years
• Affiliated to social security

Exclusion Criteria:

• Refusal to participate in the study
• DAS28 < 3.2
• Patient under guardianship
• Participation in another protocol without agreement of the dentist
• Not affiliated to social security

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Periodontal prophylaxis; Periodontal prophylaxis (standard of care) versus control in rheumatoid arthritis patients.	Other: Periodontal prophylaxis; 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; Other Names: Mouthrinse: Listerine®; toothpaste: Colgate Total®
Control; Periodontal prophylaxis (standard of care) versus control in rheumatoid arthritis patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Periodontal prophylaxis	Assessment of the effect of an intervention : periodontal prophylaxis (periodontal scaling + mouthwash + toothpaste)	at 12 months
Bacterial identification	Assessment of the effect of an intervention: Bacterial identification. A bacterial sampling at 4 deepest periodontal pockets will be carried.	at 12 months
Disease activity score (DAS) 28		at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of anti-citrulline and anti P. gingivalis antibodies	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.	at 12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Société Française de Parodontologie et d'Implantologie Orale (SFPIO)
• Investigators: Study Chair: Xavier MARIETTE, MD, PhD, Paris-Sud University, AP-HP; Principal Investigator: Philippe BOUCHARD, MD, PhD, Paris Diderot University, AP-HP; Principal Investigator: Philippe RAVAUD, MD, PhD, Paris Descartes University, AP-HP

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2012
• Primary Completion (Actual): September 7, 2016
• Study Completion (Actual): July 26, 2017

Study Registration Dates

• First Submitted: September 14, 2012
• First Submitted That Met QC Criteria: October 12, 2012
• First Posted (Estimate): October 15, 2012

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: July 31, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; Prophylaxis; Periodontal disease; Plaque control; P.gingivalis; Oral hygiene instruction
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Anti-Infective Agents, Local; Anti-Infective Agents; Listerine
• Other Study ID Numbers: 2011- AO1271 - 40

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No