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

This study has been completed.
Sponsor:
Collaborators:
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT01198509
First received: September 8, 2010
Last updated: December 31, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention
Rheumatoid Arthritis
Psoriatic Arthritis
Periodontal Disease
Drug: doxycycline
Drug: vancomycin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Official Title: Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Alteration of Microbiota, Alteration of T Cell Function/Activation [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Mean Units Change in DAS28 From Baseline to 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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).



Enrollment: 178
Study Start Date: January 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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.


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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198509

Locations
United States, New York
Bellevue Hospital
New York, New York, United States, 10016
NYU Hospital for Joint Diseases
New York, New York, United States, 10003
Sponsors and Collaborators
New York University School of Medicine
Memorial Sloan Kettering Cancer Center
Investigators
Principal Investigator: Steven B. Abramson, MD New York University School of Medicine
Study Director: Jose U. Scher, MD New York University School of Medicine
  More Information

Additional Information:
Publications:

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01198509     History of Changes
Other Study ID Numbers: 09-0658, RC2AR058986
Study First Received: September 8, 2010
Results First Received: September 3, 2014
Last Updated: December 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
rheumatoid arthritis
psoriatic arthritis
periodontitis
microbiota
microbiome
vancomycin
doxycycline
T cell
Th17

Additional relevant MeSH terms:
Arthritis
Arthritis, Psoriatic
Arthritis, Rheumatoid
Gingival Diseases
Periodontal Diseases
Autoimmune Diseases
Bone Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Mouth Diseases
Musculoskeletal Diseases
Psoriasis
Rheumatic Diseases
Skin Diseases
Skin Diseases, Papulosquamous
Spinal Diseases
Spondylarthritis
Spondylarthropathies
Spondylitis
Stomatognathic Diseases
Doxycycline
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 29, 2015