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

NCT ID: NCT01198509

Last Updated: 2015-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2013-01-31

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.

Detailed Description

If you would like to participate in this study, we will first ask you several questions regarding the status of your arthritis, the medications you use or have used in the recent past, your social and dietary habits, and your medical and surgical history. If your answers tell us that you are the right patient for our study, we will go over a consent form which describes in more detail how we will study your intestinal and mouth bacteria, the immune cells in your blood and other genes, enzymes and proteins that tell us about your disease status.

If you have Psoriatic Arthritis (PsA) or are healthy with no history of arthritis, and would like to participate in this study, your participation would involve only one or two visits, and no treatment.

If you have Rheumatoid Arthritis (RA), your participation would involve six visits, and you would be randomly assigned to receive treatment with the antibiotic doxycycline, or the antibiotic vancomycin, or no antibiotic treatment.

Conditions

Rheumatoid Arthritis; Psoriatic Arthritis; Periodontal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: SINGLE

Study Groups

Rheumatoid Arthritis (RA) - doxycycline

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

Group Type: ACTIVE_COMPARATOR

doxycycline

Intervention Type: DRUG

doxycycline - 100 mg twice per day, for 2 months

Rheumatoid Arthritis (RA) - vancomycin

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

Group Type: ACTIVE_COMPARATOR

vancomycin

Intervention Type: DRUG

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

RA, PsA, healthy

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

doxycycline

doxycycline - 100 mg twice per day, for 2 months

Intervention Type: DRUG

vancomycin

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

Intervention Type: DRUG

Other Intervention Names

Vibramycin; Vancocin

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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)
• Renal: Creatinine >1.5 or endstage renal disease
• Peptic ulcer disease: recent ulcer or GI bleed (within past 12 months)
• Inability or unwillingness to abstain from alcohol consumption.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven B. Abramson, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Jose U. Scher, MD

Role: STUDY_DIRECTOR

NYU Langone Health

Locations

NYU Hospital for Joint Diseases

New York, New York, United States

Bellevue Hospital

New York, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 21862983 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22224764 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22018232 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24247114 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24229458 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22576262 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21393509 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24192039 (View on PubMed)

Other Identifiers

RC2AR058986

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-0658

Identifier Type: -

Identifier Source: org_study_id