Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)

NCT01198509 | Completed Results DMC

• 2 other identifiers: 09-0658RC2AR058986
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 2

Brief Summary

Rheumatoid arthritis (RA) is an inflammatory form of arthritis that causes joint pain and damage. RA attacks the lining of the joints (synovium), causing swelling that can result in aching and throbbing, and eventually deformity. Even though there have been many advances in the treatment of RA, psoriatic arthritis (PsA), and other inflammatory arthritis, doctors still do not know what causes this inflammation in joints. It is likely that RA occurs as a result of a complex combination of factors, including a person's genes; lifestyle choices, such as smoking and diet; and things in a person's environment, including bacteria or viruses. This study investigates the hypothesis that bacteria living in a person's mouth and/or intestinal tract are responsible, at least in part, for the development of Rheumatoid Arthritis. The investigators believe that by killing those bacteria with antibiotics, they might be able to understand how the immune system works and, maybe, what causes RA.

Conditions

Rheumatoid Arthritis; Psoriatic Arthritis; Periodontal Disease

Keywords

rheumatoid arthritis; psoriatic arthritis; periodontitis; microbiota; microbiome; vancomycin; doxycycline; T cell; Th17

Outcome Measures

Primary Outcomes (1)

• Alteration of Microbiota, Alteration of T Cell Function/Activation

  Oral and intestinal microbiota, and T cell function and activation, will be assessed at baseline, and at 1, 2, 3, 4 and 5 months after baseline, to determine whether changes are associated with vancomycin treatment versus doxycycline treatment versus no treatment. Results are reported as number of participants who experienced changes in oral/intestinal microbiota, T cell function/activation. Methods/criteria to assess change in microbiota: change in relative abundance of microorganisms at genus and species level (as assessed high-throughput 16S rDNA sequencing). Methods/criteria to assess change in T cell function/activation: change in percentage of inhibition of regulatory T cells as measured by interferon gamma levels in in-vitro assays.

  6 months

Secondary Outcomes (1)

• Mean Units Change in DAS28 From Baseline to 6 Months

  6 months

Study Arms (3)

Rheumatoid Arthritis (RA) - doxycycline

ACTIVE COMPARATOR

Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive doxycycline, 100 mg twice a day, for 2 months.

Drug: doxycycline

Rheumatoid Arthritis (RA) - vancomycin

ACTIVE COMPARATOR

Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive vancomycin, 250 mg four times a day, for 2 weeks

Drug: vancomycin

RA, PsA, healthy

NO INTERVENTION

Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive no antibiotic treatment for comparison with Doxycycline- and Vancomycin-treated patients. Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients. Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.

Interventions

doxycycline DRUG

doxycycline - 100 mg twice per day, for 2 months

Also known as: Vibramycin

Rheumatoid Arthritis (RA) - doxycycline

vancomycin DRUG

vancomycin, 250 mg four times a day, for 2 weeks

Also known as: Vancocin

Rheumatoid Arthritis (RA) - vancomycin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Rheumatoid Arthritis (RA) patients must meet American College of Rheumatology (ACR) criteria for RA
• RA patients: duration of disease will be greater than 6 weeks and less than 2 years.
• RA patients should have a Disease Activity Score 28 (DAS28) greater than or equal to 5.
• PsA patients will be required to have disease duration and DAS28 similar to the RA patients, and to meet Moll and Wright criteria for PsA.
• Allowable medications for both groups at study entry will include: prednisone (or equivalent) 5 mg or less per day (stable dose for at least 2 months); methotrexate 15 mg or less per week (stable dose for at least 2 months); and nonsteroidal anti-inflammatory drugs (NSAIDs) at FDA-approved doses.
• Healthy controls will be age- and sex-matched individuals with no personal or family history of inflammatory arthritis.

You may not qualify if:

• Patients who are unable to provide informed consent.
• Pregnant or lactating women.
• Recent (\<3 months prior) use of any antibiotic therapy
• Current consumption of probiotics
• Current extreme diet (parenteral nutrition, macrobiotic diet, etc.)
• Prednisone \>5 mg/day or equivalent
• Use of other disease-modifying antirheumatic drugs (DMARDs) with known antibiotic properties (Gold salts, hydroxychloroquine, sulfasalazine or minocycline).
• Use of biologic DMARDs
• Known inflammatory bowel disease
• Known gastrointestinal (GI) tract neoplasm.
• Recent GI tract infection (gastroenteritis, colitis, diverticulitis, appendicitis)
• Chronic unexplained diarrhea.
• Any GI tract surgery leaving permanent residua (e.g., gastrectomy; bariatric surgery; colectomy)
• Significant liver, renal or peptic ulcer disease, defined as:
• Liver: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN)

Sponsors & Collaborators

• NYU Langone Health: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (2)

NYU Hospital for Joint Diseases

New York, New York, 10003, United States

Location

Bellevue Hospital

New York, New York, 10016, United States

Location

Related Publications (8)

• Scher JU, Abramson SB. The microbiome and rheumatoid arthritis. Nat Rev Rheumatol. 2011 Aug 23;7(10):569-78. doi: 10.1038/nrrheum.2011.121.

  PMID: 21862983 BACKGROUND

• Honda K, Littman DR. The microbiome in infectious disease and inflammation. Annu Rev Immunol. 2012;30:759-95. doi: 10.1146/annurev-immunol-020711-074937. Epub 2012 Jan 6.

  PMID: 22224764 BACKGROUND

• Littman DR, Pamer EG. Role of the commensal microbiota in normal and pathogenic host immune responses. Cell Host Microbe. 2011 Oct 20;10(4):311-23. doi: 10.1016/j.chom.2011.10.004.

  PMID: 22018232 BACKGROUND

• Brusca SB, Abramson SB, Scher JU. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol. 2014 Jan;26(1):101-7. doi: 10.1097/BOR.0000000000000008.

  PMID: 24247114 BACKGROUND

• Scher JU, Abramson SB. Periodontal disease, Porphyromonas gingivalis, and rheumatoid arthritis: what triggers autoimmunity and clinical disease? Arthritis Res Ther. 2013;15(5):122. doi: 10.1186/ar4360.

  PMID: 24229458 BACKGROUND

• Scher JU, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A, Lipuma L, Attur M, Pillinger MH, Weissmann G, Littman DR, Pamer EG, Bretz WA, Abramson SB. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012 Oct;64(10):3083-94. doi: 10.1002/art.34539.

  PMID: 22576262 RESULT

• Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, Su J, Yin F, Ding AH, Zanin-Zhorov A, Dustin ML, Tao J, Craft J, Yin Z, Feng JQ, Abramson SB, Yu XP, Liu CJ. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011 Apr 22;332(6028):478-84. doi: 10.1126/science.1199214. Epub 2011 Mar 10.

  PMID: 21393509 RESULT

• Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, Rostron T, Cerundolo V, Pamer EG, Abramson SB, Huttenhower C, Littman DR. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013 Nov 5;2:e01202. doi: 10.7554/eLife.01202.

  PMID: 24192039 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis, Psoriatic; Periodontal Diseases; Periodontitis

Interventions

Doxycycline; Vancomycin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Interpretation of results is limited by very small sample size. It should be noted that this was intended as a proof-of-concept study, and not a fully-powered clinical trial.

Results Point of Contact

• Title: Steven B. Abramson, MD
• Organization: New York University School of Medicine

StevenB.Abramson@nyumc.org

212-263-8003

Study Officials

• Steven B. Abramson, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

• Jose U. Scher, MD

  NYU Langone Health

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2010
• First Posted: September 10, 2010
• Study Start: January 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: January 13, 2015
• Results First Posted: January 13, 2015

Record last verified: 2014-12

Locations

US (2)