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

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ClinicalTrials.gov Identifier: NCT01198509
Recruitment Status : Completed
First Posted : September 10, 2010
Results First Posted : January 13, 2015
Last Update Posted : January 13, 2015
Sponsor:
Collaborators:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Memorial Sloan Kettering Cancer Center
Information provided by (Responsible Party):
New York University School of Medicine

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor)
Conditions Rheumatoid Arthritis
Psoriatic Arthritis
Periodontal Disease
Interventions Drug: doxycycline
Drug: vancomycin
Enrollment 178

Recruitment Details Dates of recruitment period: January 2010 - August 2012 Locations: Medical clinics and faculty practice offices
Pre-assignment Details  
Arm/Group Title Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin Rheumatoid Arthritis (RA) Randomized to no Treatment Early RA Cross-sectional Cohort Psoriatic Arthritis (PsA) Healthy Volunteers
Hide Arm/Group Description

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)

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)

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)

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)

Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.

N=20 (actual)

Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.

N=58 (actual)

Period Title: Overall Study
Started 5 10 19 66 20 58
Completed 4 [1] 10 19 66 20 58
Not Completed 1 0 0 0 0 0
Reason Not Completed
Withdrawal by Subject             1             0             0             0             0             0
[1]
Patient declined further participation after enrollment and allocation to treatment group
Arm/Group Title Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin Rheumatoid Arthritis (RA) Randomized to no Treatment Early RA Cross-sectional Cohort Psoriatic Arthritis (PsA) Healthy Volunteers Total
Hide Arm/Group Description

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

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

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. 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). 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. Total of all reporting groups
Overall Number of Baseline Participants 5 10 19 66 20 58 178
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants 10 participants 19 participants 66 participants 20 participants 58 participants 178 participants
44.0
(31 to 68)
41.5
(24 to 63)
39.2
(26 to 69)
49.1
(20 to 85)
45.5
(26 to 73)
40.7
(21 to 62)
44.2
(20 to 85)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 10 participants 19 participants 66 participants 20 participants 58 participants 178 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
  80.0%
10
 100.0%
18
  94.7%
58
  87.9%
19
  95.0%
58
 100.0%
167
  93.8%
>=65 years
1
  20.0%
0
   0.0%
1
   5.3%
8
  12.1%
1
   5.0%
0
   0.0%
11
   6.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 10 participants 19 participants 66 participants 20 participants 58 participants 178 participants
Female
4
  80.0%
7
  70.0%
14
  73.7%
53
  80.3%
11
  55.0%
50
  86.2%
139
  78.1%
Male
1
  20.0%
3
  30.0%
5
  26.3%
13
  19.7%
9
  45.0%
8
  13.8%
39
  21.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 10 participants 19 participants 66 participants 20 participants 58 participants 178 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
  10.0%
3
  15.8%
4
   6.1%
5
  25.0%
2
   3.4%
15
   8.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  40.0%
1
  10.0%
1
   5.3%
17
  25.8%
1
   5.0%
9
  15.5%
31
  17.4%
White
1
  20.0%
2
  20.0%
1
   5.3%
16
  24.2%
6
  30.0%
12
  20.7%
38
  21.3%
More than one race
2
  40.0%
6
  60.0%
14
  73.7%
29
  43.9%
8
  40.0%
35
  60.3%
94
  52.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 10 participants 19 participants 66 participants 20 participants 58 participants 178 participants
Hispanic or Latino
3
  60.0%
7
  70.0%
15
  78.9%
41
  62.1%
8
  40.0%
43
  74.1%
117
  65.7%
Not Hispanic or Latino
2
  40.0%
3
  30.0%
4
  21.1%
25
  37.9%
12
  60.0%
15
  25.9%
61
  34.3%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 5 participants 10 participants 19 participants 66 participants 20 participants 58 participants 178 participants
5 10 19 66 20 58 178
1.Primary Outcome
Title Alteration of Microbiota, Alteration of T Cell Function/Activation
Hide Description

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.

Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin Rheumatoid Arthritis (RA) Randomized to no Treatment Early RA Cross-sectional Cohort Psoriatic Arthritis (PsA) Healthy Volunteers
Hide Arm/Group Description:

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

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

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)

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)

Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.

N=20 (actual)

Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.

N=58 (actual)

Overall Number of Participants Analyzed 4 10 19 66 20 58
Measure Type: Number
Unit of Measure: participants
Change in oral/intestinal microbiota 4 10 2 0 0 0
Change in T cell function/activation 2 6 19 0 0 0
2.Secondary Outcome
Title Mean Units Change in DAS28 From Baseline to 6 Months
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin Rheumatoid Arthritis (RA) Randomized to no Treatment Early RA Cross-sectional Cohort Psoriatic Arthritis (PsA) Healthy Volunteers
Hide Arm/Group Description:

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

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

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.

N=19 (actual)

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)

Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.

N=20 (actual)

Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.

N=58 (actual)

Overall Number of Participants Analyzed 4 10 19 0 0 0
Mean (Full Range)
Unit of Measure: units on a scale
-1.3
(-1.7 to -0.4)
-1.5
(-4.4 to -0.2)
-2.5
(-3.9 to -0.9)
Time Frame Duration of the study, up to 6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin RA, PsA, Healthy
Hide Arm/Group Description

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

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

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.

All-Cause Mortality
Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin RA, PsA, Healthy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin RA, PsA, Healthy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/4 (0.00%)      0/10 (0.00%)      0/163 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rheumatoid Arthritis (RA) - Doxycycline Rheumatoid Arthritis (RA) - Vancomycin RA, PsA, Healthy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/4 (0.00%)      1/10 (10.00%)      0/163 (0.00%)    
Gastrointestinal disorders       
stomach pain/loose stools  1 [1]  0/4 (0.00%)  0 1/10 (10.00%)  1 0/163 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, Other
[1]
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.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Steven B. Abramson, MD
Organization: New York University School of Medicine
Phone: 212-263-8003
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT01198509     History of Changes
Other Study ID Numbers: 09-0658
RC2AR058986 ( U.S. NIH Grant/Contract )
First Submitted: September 8, 2010
First Posted: September 10, 2010
Results First Submitted: September 3, 2014
Results First Posted: January 13, 2015
Last Update Posted: January 13, 2015