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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01198509
• Other study ID #: 09-0658
• Secondary ID: RC2AR058986
• Status: Completed
• Phase: N/A
• First received: September 8, 2010
• Last updated: December 31, 2014
• Start date: January 2010
• Est. completion date: January 2013

Study information

• Verified date: December 2014
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor)

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Arthritis, Rheumatoid
• Gingival Diseases
• Periodontal Disease
• Periodontal Diseases
• Psoriatic Arthritis
• Rheumatoid Arthritis

Intervention

Drug:
• doxycycline
doxycycline - 100 mg twice per day, for 2 months
• vancomycin
vancomycin, 250 mg four times a day, for 2 weeks

Locations

Country	Name	City	State
United States	Bellevue Hospital	New York	New York
United States	NYU Hospital for Joint Diseases	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
New York University School of Medicine	Memorial Sloan Kettering Cancer Center, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Scher JU, Abramson SB. Periodontal disease, Porphyromonas gingivalis, and rheumatoid arthritis: what triggers autoimmunity and clinical disease? Arthritis Res Ther. 2013;15(5):122. — View Citation

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. Review. — View Citation

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:e0 — View Citation

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 — View Citation

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 therap — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Mean Units Change in DAS28 From Baseline to 6 Months	DAS28 (disease activity score with 28 joint count). Possible score range: 0 to 10. This is a composite index calculated from 4 measures: two from a physician (28 tender joint count, 28 swollen joint count), one from the patient (patient global estimate of disease activity), and one laboratory biomarker (erythrocyte sedimentation rate or ESR). A score of 0 represents best possible health status (no apparent disease activity) and 10 represents worst possible.; The outcome is reported as mean change in DAS28 score from baseline to 6 months. The mean changes reported are negative values for downward change in score (i.e., improvement in health status).	6 months	No