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| ID | Type | Description | Link |
|---|---|---|---|
| RC2AR058986 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) | NIH |
| Memorial Sloan Kettering Cancer Center | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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 |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| doxycycline | Drug | doxycycline - 100 mg twice per day, for 2 months |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
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:
Inability or unwillingness to abstain from alcohol consumption.
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| Name | Affiliation | Role |
|---|---|---|
| Steven B. Abramson, MD | NYU Langone Health | Principal Investigator |
| Jose U. Scher, MD | NYU Langone Health | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NYU Hospital for Joint Diseases | New York | New York | 10003 | United States | ||
| Bellevue Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21862983 | Background | 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. | |
| 22224764 | Background | 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. |
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Dates of recruitment period: January 2010 - August 2012 Locations: Medical clinics and faculty practice offices
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| ID | Title | Description |
|---|---|---|
| FG000 | Rheumatoid Arthritis (RA) - Doxycycline | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive doxycycline, 100 mg twice a day, for 2 months. doxycycline: doxycycline - 100 mg twice per day, for 2 months N=5 (actual) |
| FG001 | 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 vancomycin: vancomycin, 250 mg four times a day, for 2 weeks N=10 (actual) |
| FG002 | Rheumatoid Arthritis (RA) Randomized to no Treatment | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive no antibiotic treatment for comparison with Doxycycline- and Vancomycin-treated patients. N=19 (actual) |
| FG003 | Early RA Cross-sectional Cohort | Patients with rheumatoid arthritis (RA) meeting inclusion criteria who opted to participate ONLY in cross-sectional analysis (one-time sample collection equivalent to the involvement of PsA and health control subjects). N=66 (actual) |
| FG004 | Psoriatic Arthritis (PsA) | Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients. N=20 (actual) |
| FG005 | Healthy Volunteers | Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients. N=58 (actual) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rheumatoid Arthritis (RA) - Doxycycline | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive doxycycline, 100 mg twice a day, for 2 months. doxycycline: doxycycline - 100 mg twice per day, for 2 months |
| BG001 | Rheumatoid Arthritis (RA) - Vancomycin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Primary outcome only evaluated in first three groups of RA patients: 4 randomized to treatment with doxycycline; 10 randomized to treatment with vancomycin; 19 randomized to no treatment. | Posted | Number | participants | 6 months |
|
Duration of the study, up to 6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rheumatoid Arthritis (RA) - Doxycycline | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive doxycycline, 100 mg twice a day, for 2 months. doxycycline: doxycycline - 100 mg twice per day, for 2 months |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| stomach pain/loose stools | Gastrointestinal disorders | Other | Systematic Assessment | Resolved within 24 hours. Possibly related to study treatment. Participant continued treatment and completed study. |
Interpretation of results is limited by very small sample size. It should be noted that this was intended as a proof-of-concept study, and not a fully-powered clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Steven B. Abramson, MD | New York University School of Medicine | 212-263-8003 | StevenB.Abramson@nyumc.org |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D015535 | Arthritis, Psoriatic |
| D010510 | Periodontal Diseases |
| D010518 | Periodontitis |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D004318 | Doxycycline |
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| vancomycin | Drug | vancomycin, 250 mg four times a day, for 2 weeks |
|
|
| 6 months |
| New York |
| New York |
| 10016 |
| United States |
| 22018232 | Background | 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. |
| 24247114 | Background | 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. |
| 24229458 | Background | Scher 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. |
| 22576262 | Result | 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;64(10):3083-94. doi: 10.1002/art.34539. |
| 21393509 | Result | 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 therapeutic against inflammatory arthritis in mice. Science. 2011 Apr 22;332(6028):478-84. doi: 10.1126/science.1199214. Epub 2011 Mar 10. |
| 24192039 | Result | 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:e01202. doi: 10.7554/eLife.01202. |
Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive vancomycin, 250 mg four times a day, for 2 weeks vancomycin: vancomycin, 250 mg four times a day, for 2 weeks |
| BG002 | Rheumatoid Arthritis (RA) Randomized to no Treatment | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive no antibiotic treatment and followed prospectively for 6 months, for comparison with Doxycycline- and Vancomycin-treated patients. |
| BG003 | Early RA Cross-sectional Cohort | Patients with rheumatoid arthritis (RA) meeting inclusion criteria who opted to participate ONLY in cross-sectional analysis (one-time sample collection equivalent to the involvement of PsA and health control subjects). |
| BG004 | Psoriatic Arthritis (PsA) | Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients. |
| BG005 | Healthy Volunteers | Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients. |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 |
| Rheumatoid Arthritis (RA) - Doxycycline |
Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive doxycycline, 100 mg twice a day, for 2 months. doxycycline: doxycycline - 100 mg twice per day, for 2 months |
| OG001 | 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 vancomycin: vancomycin, 250 mg four times a day, for 2 weeks |
| OG002 | Rheumatoid Arthritis (RA) Randomized to no Treatment | Patients with rheumatoid arthritis (RA) meeting inclusion criteria, randomized to receive no antibiotic treatment, followed prospectively for 6 months, for comparison with Doxycycline- and Vancomycin-treated patients. N=19 (actual) |
| OG003 | Early RA Cross-sectional Cohort | Patients with rheumatoid arthritis (RA) meeting inclusion criteria who opted to participate ONLY in cross-sectional analysis (one-time sample collection equivalent to the involvement of PsA and health control subjects). N=66 (actual) |
| OG004 | Psoriatic Arthritis (PsA) | Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients. N=20 (actual) |
| OG005 | Healthy Volunteers | Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients. N=58 (actual) |
|
|
| 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). | Please note that only the first 3 groups (RA doxycycline, RA vancomycin, and RA randomized to no treatment) were analyzed for change from baseline to six months (outcomes). Groups 4, 5 and 6 (RA cross-sectional, Psoriatic Arthritis, and Healthy Volunteers) were analyzed for baseline measures only in a cross-sectional comparison. | Posted | Mean | Full Range | units on a scale | 6 months |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| EG001 | 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 vancomycin: vancomycin, 250 mg four times a day, for 2 weeks | 0 | 10 | 1 | 10 |
| EG002 | 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. | 0 | 163 | 0 | 163 |
|
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| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D025242 | Spondylarthropathies |
| D025241 | Spondylarthritis |
| D013166 | Spondylitis |
| D013122 | Spinal Diseases |
| D001847 | Bone Diseases |
| D011565 | Psoriasis |
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |