Rheumatoid ArthritisNCT01198509
Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)
A study testing doxycycline and vancomycin in people with Rheumatoid Arthritis and Psoriatic Arthritis, run by NYU Langone Health at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis, Psoriatic Arthritis, Periodontal Disease
- What is being tested?
- doxycycline and vancomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 178 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2010to Jan 2013
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
NYU Hospital for Joint Diseases
New York, New York, 10003
Bellevue Hospital
New York, New York, 10016
About this study
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.
Read the 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.
- Being tested
- doxycycline, vancomycin
- Keywords
- rheumatoid arthritis, psoriatic arthritis, periodontitis, microbiota, microbiome, vancomycin, doxycycline, T cell, Th17
- Medical subject headings
- Arthritis, Rheumatoid, Arthritis, Psoriatic, Periodontal Diseases, Periodontitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
doxycyclineDrug
Also called Vibramycin
doxycycline - 100 mg twice per day, for 2 months
vancomycinDrug
Also called Vancocin
vancomycin, 250 mg four times a day, for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Rheumatoid Arthritis (RA) - doxycycline | Active comparator | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive doxycycline, 100 mg twice a day, for 2 months. Receives: Drug: doxycycline |
| Rheumatoid Arthritis (RA) - vancomycin | Active comparator | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive vancomycin, 250 mg four times a day, for 2 weeks Receives: Drug: vancomycin |
| RA, PsA, healthy | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (1)
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).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2010 (estimated)
- Study startJan 2010
- Primary completionJan 2013
- Study completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 178 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Memorial Sloan Kettering Cancer Center
- Responsible party
- Sponsor
- Investigators
- Steven B. Abramson, MD, Principal investigator, NYU Langone HealthJose U. Scher, MD, Study director, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01198509
- Sponsor's protocol ID
- 09-0658
- Other IDs
- RC2AR058986
- Status last verified
- Dec 2014
- First submitted
- 8 Sep 2010
- Last updated
- 13 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 21862983Honda 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.
PubMed 22224764Littman 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.
PubMed 22018232Brusca 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.
PubMed 24247114Scher 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.
PubMed 24229458Scher 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.
PubMed 22576262Tang 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.
PubMed 21393509Scher 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.
PubMed 24192039