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

December 31, 2014 updated by: NYU Langone Health
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • Bellevue Hospital
      • New York, New York, United States, 10003
        • NYU Hospital for Joint Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Rheumatoid Arthritis (RA) - doxycycline
Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive doxycycline, 100 mg twice a day, for 2 months.
Drug: doxycycline
doxycycline - 100 mg twice per day, for 2 months
Other Names:
  • Vibramycin
Active Comparator: 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
Drug: vancomycin
vancomycin, 250 mg four times a day, for 2 weeks
Other Names:
  • Vancocin
No Intervention: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Alteration of Microbiota, Alteration of T Cell Function/Activation
Time Frame: 6 months

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Units Change in DAS28 From Baseline to 6 Months
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Collaborators

Memorial Sloan Kettering Cancer Center
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

  • Principal Investigator: Steven B. Abramson, MD, NYU Langone Health
  • Study Director: Jose U. Scher, MD, NYU Langone Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

September 8, 2010

First Submitted That Met QC Criteria

September 8, 2010

First Posted (Estimate)

September 10, 2010

Study Record Updates

Last Update Posted (Estimate)

January 13, 2015

Last Update Submitted That Met QC Criteria

December 31, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-0658
  • RC2AR058986 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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