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)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Improvement in the rheumatoid arthritis disease activity index (DAS28ESR-3v) by >=1.2 points
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •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
- •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
- •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
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Improvement in the clinical disease activity index cDAI(After 3 and 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(After 3 and 6 months)
- Improvement in the simplified disease activity index cDAI(After 3 and 6 months)
- Reduction in the number of sites with bleeding on probing (BoP)(After 3 and 6 months)
- Improvement in the rheumatoid arthritis disease activity score (DAS28ESR-3v) by >=1.2 points(At 6 months)
- Number of patients with 20%, 50% or 70% improvement in the American College of Rheumatology (ACR) response criteria(After 3 and 6 months)
- % change of B-mode (= gray-scale) and Power-Doppler signals to baseline(After 3 and 6 months)
- Number of patients in ACR/EULAR remission(After 3 and 6 months)
- Reduction in the probing pocket depth (PPD) in moderately deep (PPD >/= 4mm) und deep periodontal pockets (PPD > 6mm)(After 3 and 6 months)
- Improvement in clinical attachment level (CAL), as the sum of PPD plus gingival recession (GR)(After 3 and 6 months)