Full Mouth Disinfection and Antibiotics for Periodontitis in High or Moderate Disease Activity Rheumatoid Arthritis (FMD-ABRA)

October 2, 2018 updated by: University Hospital Inselspital, Berne

Single Arm Pilot Study of Antimicrobial Treatment of Active Rheumatoid Arthritis Associated With Manifest Periodontitis (Translated From German: Anti-mikrobielle Behandlung Der Aktiven Rheumatoiden Arthritis Bei Manifester Parodontitis - Eine Unkontrollierte Therapie-Pilotstudie)

The purpose of this study is to determine whether full mouth disinfection in combination with one week antibiotic amoxicillin plus metronidazole antibiotic therapy is improving periodontitis and disease activity of rheumatoid arthritis.

Study Overview

Status

Completed

Conditions

Detailed Description

Rheumatoid arthritis (RA) is a currently incurable disease of unknown origin characterized by joint inflammation and the breakdown of immune tolerance to a variety of antigens, including citrullinated peptides generated by peptidyl-arginine-deiminases (PAD's). Porphyromonas gingivalis (P. g.) derived PAD enzyme (PPAD) citrullinates preferentially C-terminal arginine residues, which may be generated by P.g. derived gingipain protein (Rgpb) cleavage, but several of the originated peptide sequences from enolase, collagen, vimentin or fibrinogen may be cross-reactant to citrullinated RA candidate autoantigens.

Antigen-specific autoantibodies in RA may be present years before clinical disease onset of arthritis, and their precise role in the initiation or perpetuation of the characteristic articular immune processes is currently unclear. The situation for autoantibodies was in similar poorly understood for decades until an unanticipated reduction of RA disease activity could be achieved by therapeutic B cell depletion using anti-CD20 therapy. While anti-CD20 therapy may affect the regeneration of autoantibody producing cells, the investigators aim in the present study to reduce potential oral trigger mechanisms or antigens for cross-reactant autoreactive B cell or plasma cell populations. The study follows the concept of improved RA disease activity by minimization of any inflammatory stimuli associated with periodontitis, e.g. by any underlying microbial colonization, the amount of microbial foreign antigens, achieved by standard oral hygienic means, full mouth disinfection plus adjuvant short term antibiotic therapy in established periodontitis.

Study Type

Observational

Enrollment (Actual)

8

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • Inselspital, Department for Rheumatology, and Dpt. For Periodontology, School for Dentistry, University of Bern

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients will be recruited from inpatient and outpatient hospital rheumatology departments.

Description

Inclusion Criteria:

  • Written informed consent
  • Age 18 years or older
  • Diagnosis of rheumatoid arthritis according to the ACR/EULAR 2010 classification criteria plus both serological, high titer (>3x ULN) rheumatoid factor and CCP antibody titer
  • Severe chronic periodontitis (clinical attachment loss >/= 5mm at two separate locations)

  • DAS 28 > 4.2 at screening and inclusion (within 28 days after screening) and 1 out of two additional disease activity criteria:

    1. Synovial hyperplasia >22/66 points on basis of 22 joints, or at least 1/3 of the maximum score when analyzes in at least selected 5 joints of interest OR
    2. Serum CRP > 10 mg/l at screening and at inclusion
  • Stable doses for >=3 months, if currently under synthetic or recombinant disease modifying anti-rheumatic drugs. If under anti-CD20 treatment: last rituximab infusion >90 days before inclusion.
  • Systemic corticosteroids <= 10 mg and stable for at least 14 days
  • Nonsteroidal-antirheumatic drugs and peripheral analgesics at stable doses for at least 14 days

Exclusion Criteria:

  • Intolerance to amoxicillin und azithromycin (EBV infection, lymphatic leukemia, exanthema), general hypersensitivity to any beta-lactam antibiotics, intolerance to metronidazole or local anaesthesia
  • Current intake of allopurinol or probenicid, oral anticoagulation, disulfiram, phenobarbital phenytoin, lithium or ciclosporin
  • Seizures
  • Severe cardial electric conduction blockade
  • Recent myocardial infraction or instable coronary vessel disease, non-compensated myocardial insufficiency or heart failure
  • Non-compensated arterial hypertension
  • Genetic cholinesterase deficiency
  • General hemorrhagic diathesis or intake of oral anticoagulants
  • Intake of monoaminooxidase inhibitors or tricyclic antidepressants
  • Liver insufficiency
  • Renal failure (eGFR < 30 ml/min)
  • Hemoglobin <10 g/dl
  • Leukocytes < 3/nl
  • Neutrophils < 1/nl
  • Platelets < 100/nl
  • ALAT oder ASAT > 3x ULN
  • Pregnancy or breastfeeding
  • Psychiatric or any other condition which could, to the opinion of the investigator, interfere with the compliance of this protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
All patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvement in the rheumatoid arthritis disease activity index (DAS28ESR-3v) by >=1.2 points
Time Frame: 3 months
The DAS28 will be used using 3 variables with 3rd variable erythrocyte sedimentation rate.
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Improvement in the rheumatoid arthritis disease activity score (DAS28ESR-3v) by >=1.2 points
Time Frame: At 6 months
At 6 months
Improvement in the rheumatoid arthritis disease activity score when with 3rd variable C reactive protein serum concentration (DAS28CRP-3v) by >=1.2 points
Time Frame: After 3 and 6 months
After 3 and 6 months
Improvement in the clinical disease activity index cDAI
Time Frame: After 3 and 6 months
After 3 and 6 months
Improvement in the simplified disease activity index cDAI
Time Frame: After 3 and 6 months
After 3 and 6 months
Number of patients with 20%, 50% or 70% improvement in the American College of Rheumatology (ACR) response criteria
Time Frame: After 3 and 6 months
After 3 and 6 months
Number of patients in ACR/EULAR remission
Time Frame: After 3 and 6 months
After 3 and 6 months
% change of B-mode (= gray-scale) and Power-Doppler signals to baseline
Time Frame: After 3 and 6 months
After 3 and 6 months
Reduction in the probing pocket depth (PPD) in moderately deep (PPD >/= 4mm) und deep periodontal pockets (PPD > 6mm)
Time Frame: After 3 and 6 months
After 3 and 6 months
Improvement in clinical attachment level (CAL), as the sum of PPD plus gingival recession (GR)
Time Frame: After 3 and 6 months
After 3 and 6 months
Reduction in the number of sites with bleeding on probing (BoP)
Time Frame: After 3 and 6 months
After 3 and 6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction in the number of periodontitis associated microbes on a semi-quantitative level
Time Frame: After 1, 3 and 6 months
DNA for Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Fusobacterium nucleatum, Tannerella forsythia, Treponema denticola, Filifactor alocis
After 1, 3 and 6 months
Concentration of TNFα, IL-1β, MMP-1 and TIMP-1 1
Time Frame: After 1, 3 und 6 months
After 1, 3 und 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

University of Bern

Investigators

  • Principal Investigator: Burkhard Möller, MD, Inselspital, Department for Rheumatology, University of Bern, 3010 Bern, Switzerland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

August 1, 2017

Study Completion (Actual)

October 25, 2017

Study Registration Dates

First Submitted

March 21, 2014

First Submitted That Met QC Criteria

March 24, 2014

First Posted (Estimate)

March 26, 2014

Study Record Updates

Last Update Posted (Actual)

October 4, 2018

Last Update Submitted That Met QC Criteria

October 2, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 130/13
  • 2439 (Inselspital)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rheumatoid Arthritis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe