Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)
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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) |
- 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.
- 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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01198509
| 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 | |
| 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 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 March 03, 2015