Full Mouth Disinfection and Antibiotics for Periodontitis in High or Moderate Disease Activity Rheumatoid Arthritis

NCT02096120 | Completed

• 2 other identifiers: 130/132439
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

Periodontitis

Outcome Measures

Primary Outcomes (1)

• Improvement in the rheumatoid arthritis disease activity index (DAS28ESR-3v) by >=1.2 points

  The DAS28 will be used using 3 variables with 3rd variable erythrocyte sedimentation rate.

  3 months

Secondary Outcomes (10)

• Improvement in the rheumatoid arthritis disease activity score (DAS28ESR-3v) by >=1.2 points

  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

  After 3 and 6 months

• Improvement in the clinical disease activity index cDAI

  After 3 and 6 months

• Improvement in the simplified disease activity index cDAI

  After 3 and 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

Other Outcomes (2)

• Reduction in the number of periodontitis associated microbes on a semi-quantitative level

  After 1, 3 and 6 months

• Concentration of TNFα, IL-1β, MMP-1 and TIMP-1 1

  After 1, 3 und 6 months

Study Arms (1)

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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)
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Bern: collaborator

Study Sites (1)

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

Bern, 3010, Switzerland

Location

Related Publications (17)

• Aimetti M, Romano F, Guzzi N, Carnevale G. Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial. J Clin Periodontol. 2012 Mar;39(3):284-94. doi: 10.1111/j.1600-051X.2011.01795.x. Epub 2012 Jan 4.

  PMID: 22220822 BACKGROUND

• Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010 Sep;69(9):1580-8. doi: 10.1136/ard.2010.138461.

  PMID: 20699241 BACKGROUND

• Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, Ronnelid J, Harris HE, Ulfgren AK, Rantapaa-Dahlqvist S, Eklund A, Padyukov L, Alfredsson L. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006 Jan;54(1):38-46. doi: 10.1002/art.21575.

  PMID: 16385494 BACKGROUND

• Lundberg K, Kinloch A, Fisher BA, Wegner N, Wait R, Charles P, Mikuls TR, Venables PJ. Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum. 2008 Oct;58(10):3009-19. doi: 10.1002/art.23936.

  PMID: 18821669 BACKGROUND

• de Pablo P, Dietrich T, Chapple IL, Milward M, Chowdhury M, Charles PJ, Buckley CD, Venables PJ. The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Ann Rheum Dis. 2014 Mar;73(3):580-6. doi: 10.1136/annrheumdis-2012-202701. Epub 2013 Feb 23.

  PMID: 23434568 BACKGROUND

• Finckh A, Müller R, Möller B, Dudler J, Kyburz D, Walker UA, et al. Tooth Loss is associated with swollen joints in a cohort of healthy individuals at increased risk of developing RA. European Congress of Rheumatology EULAR 2012. Annals of the rheumatic diseases 2012;71(Suppl).

  BACKGROUND

• Zandbergen D, Slot DE, Cobb CM, Van der Weijden FA. The clinical effect of scaling and root planing and the concomitant administration of systemic amoxicillin and metronidazole: a systematic review. J Periodontol. 2013 Mar;84(3):332-51. doi: 10.1902/jop.2012.120040. Epub 2012 May 21.

  PMID: 22612369 BACKGROUND

• Sampaio E, Rocha M, Figueiredo LC, Faveri M, Duarte PM, Gomes Lira EA, Feres M. Clinical and microbiological effects of azithromycin in the treatment of generalized chronic periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol. 2011 Sep;38(9):838-46. doi: 10.1111/j.1600-051X.2011.01766.x. Epub 2011 Jul 19.

  PMID: 21770996 BACKGROUND

• Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995 Jan;38(1):44-8. doi: 10.1002/art.1780380107.

  PMID: 7818570 BACKGROUND

• Fransen J, van Riel PL. The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S93-9.

  PMID: 16273792 BACKGROUND

• Mandl P, Naredo E, Wakefield RJ, Conaghan PG, D'Agostino MA; OMERACT Ultrasound Task Force. A systematic literature review analysis of ultrasound joint count and scoring systems to assess synovitis in rheumatoid arthritis according to the OMERACT filter. J Rheumatol. 2011 Sep;38(9):2055-62. doi: 10.3899/jrheum.110424.

  PMID: 21885517 BACKGROUND

• Aletaha D, Smolen J. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S100-8.

  PMID: 16273793 BACKGROUND

• Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R Jr, Paulus H, Strand V, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995 Jun;38(6):727-35. doi: 10.1002/art.1780380602.

  PMID: 7779114 BACKGROUND

• Felson DT, Smolen JS, Wells G, Zhang B, van Tuyl LH, Funovits J, Aletaha D, Allaart CF, Bathon J, Bombardieri S, Brooks P, Brown A, Matucci-Cerinic M, Choi H, Combe B, de Wit M, Dougados M, Emery P, Furst D, Gomez-Reino J, Hawker G, Keystone E, Khanna D, Kirwan J, Kvien TK, Landewe R, Listing J, Michaud K, Martin-Mola E, Montie P, Pincus T, Richards P, Siegel JN, Simon LS, Sokka T, Strand V, Tugwell P, Tyndall A, van der Heijde D, Verstappen S, White B, Wolfe F, Zink A, Boers M. American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials. Ann Rheum Dis. 2011 Mar;70(3):404-13. doi: 10.1136/ard.2011.149765.

  PMID: 21292833 BACKGROUND

• Brulhart L, Zufferey P, Tamborrini G, Möller B, Gerber T, Krebs A, et al. Reproducibility and feasibility of a 22 joints ultrasound score in rheumatoid arthritis: A study among rheumatologists with diverse expertise in musculoskeletal ultrasound. . Annals of the rheumatic diseases 2012;71(Suppl ).

  BACKGROUND

• Naredo E, Wakefield RJ, Iagnocco A, Terslev L, Filippucci E, Gandjbakhch F, Aegerter P, Aydin S, Backhaus M, Balint PV, Bruyn GA, Collado P, Finzel S, Freeston JE, Gutierrez M, Joshua F, Jousse-Joulin S, Kane D, Keen HI, Moller I, Mandl P, Ohrndorf S, Pineda C, Schmidt WA, Szkudlarek M, Conaghan PG, D'Agostino MA. The OMERACT ultrasound task force--status and perspectives. J Rheumatol. 2011 Sep;38(9):2063-7. doi: 10.3899/jrheum.110425.

  PMID: 21885518 BACKGROUND

• Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999 Dec;4(1):1-6. doi: 10.1902/annals.1999.4.1.1.

  PMID: 10863370 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Each 5-10 ml of whole blood, serum and RNA specimen collected in RNA stabilization tubes will be collected at screening and start, and subsequently 1, 3 and 6 months after intervention. Gingival crevicular fluid samples will be collected at start of treatment, after 3 and 6 months.

MeSH Terms

Conditions

Arthritis, Rheumatoid; Periodontitis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Burkhard Möller, MD

  Inselspital, Department for Rheumatology, University of Bern, 3010 Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: March 26, 2014
• Study Start: February 1, 2014
• Primary Completion: August 1, 2017
• Study Completion: October 25, 2017
• Last Updated: October 4, 2018

Record last verified: 2018-10

Locations

CH (1)