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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: March 11, 2014
Last verified: March 2014

September 8, 2010
March 11, 2014
January 2010
January 2013   (final data collection date for primary outcome measure)
Alteration of microbiota, T cell function and 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.
Alteration of microbiota, T cell function and activation [ Time Frame: Baseline, 1, 2, 3, 4 and 5 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.
Complete list of historical versions of study NCT01198509 on ClinicalTrials.gov Archive Site
  • Rheumatoid arthritis (RA) biomarkers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Rheumatoid arthritis (RA) biomarkers -- including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), and biomarkers of bone and cartilage turnover -- 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.
  • Rheumatoid arthritis (RA) clinical activity data [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Rheumatoid arthritis (RA) clinical activity -- as evaluated by Disease Activity Score (DAS28) which includes 28 tender joint count and 28 swollen joint count, and by Routine Assessment of Patient Index Data (RAPID3) which includes patient-reported scores for physical function, global status, and a pain visual analog scale (VAS) -- 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.
  • Rheumatoid arthritis (RA) biomarkers [ Time Frame: Baseline, 1, 2, 3, 4 and 5 months ] [ Designated as safety issue: No ]
    Rheumatoid arthritis (RA) biomarkers -- including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), anti-CCP antibodies, C-reactive protein (CRP), and biomarkers of bone and cartilage turnover -- 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.
  • Rheumatoid arthritis (RA) clinical activity data [ Time Frame: Baseline, 1, 2, 3, 4 and 5 months ] [ Designated as safety issue: No ]
    Rheumatoid arthritis (RA) clinical activity -- as evaluated by DAS28 (disease activity score) which includes a tender and swollen joint count, and by RAPID3 (routine assessment of patient index data) which includes patient-reported scores for physical function, global status, and a pain visual analog scale (VAS) -- 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.
Not Provided
Not Provided
 
Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)
Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
  • Rheumatoid Arthritis
  • Psoriatic Arthritis
  • Periodontal Disease
  • Drug: doxycycline
    doxycycline - 100 mg twice per day, for 2 months
  • Drug: vancomycin
    vancomycin, 250 mg four times a day, for 2 weeks
  • 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.
    Intervention: Drug: doxycycline
  • 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
    Intervention: Drug: vancomycin
  • 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.


*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
178
January 2013
January 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01198509
09-0658, RC2AR058986
Yes
New York University School of Medicine
New York University School of Medicine
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • Memorial Sloan-Kettering Cancer Center
Principal Investigator: Steven B. Abramson, MD New York University School of Medicine
Study Director: Jose U. Scher, MD New York University School of Medicine
New York University School of Medicine
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP