Trial Outcomes & Findings for Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA) (NCT NCT01198509)
NCT ID: NCT01198509
Last Updated: 2015-01-13
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
178 participants
Primary outcome timeframe
6 months
Results posted on
2015-01-13
Participant Flow
Dates of recruitment period: January 2010 - August 2012 Locations: Medical clinics and faculty practice offices
Participant milestones
| Measure |
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
10
|
19
|
66
|
20
|
58
|
|
Overall Study
COMPLETED
|
4
|
10
|
19
|
66
|
20
|
58
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Role of Oral and Intestinal Microbiota in Rheumatoid Arthritis (RA)
Baseline characteristics by cohort
| Measure |
Rheumatoid Arthritis (RA) - Doxycycline
n=5 Participants
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
|
Rheumatoid Arthritis (RA) - Vancomycin
n=10 Participants
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
|
Rheumatoid Arthritis (RA) Randomized to no Treatment
n=19 Participants
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.
|
Early RA Cross-sectional Cohort
n=66 Participants
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).
|
Psoriatic Arthritis (PsA)
n=20 Participants
Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.
|
Healthy Volunteers
n=58 Participants
Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.
|
Total
n=178 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
44.0 years
n=5 Participants
|
41.5 years
n=7 Participants
|
39.2 years
n=5 Participants
|
49.1 years
n=4 Participants
|
45.5 years
n=21 Participants
|
40.7 years
n=8 Participants
|
44.2 years
n=8 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
58 Participants
n=8 Participants
|
167 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
11 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
53 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
50 Participants
n=8 Participants
|
139 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
8 Participants
n=8 Participants
|
39 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
15 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
31 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
12 Participants
n=8 Participants
|
38 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
35 Participants
n=8 Participants
|
94 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
43 Participants
n=8 Participants
|
117 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
15 Participants
n=8 Participants
|
61 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
10 participants
n=7 Participants
|
19 participants
n=5 Participants
|
66 participants
n=4 Participants
|
20 participants
n=21 Participants
|
58 participants
n=8 Participants
|
178 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: 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.
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.
Outcome measures
| Measure |
Rheumatoid Arthritis (RA) - Doxycycline
n=4 Participants
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
|
Rheumatoid Arthritis (RA) - Vancomycin
n=10 Participants
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
|
Rheumatoid Arthritis (RA) Randomized to no Treatment
n=19 Participants
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)
|
Early RA Cross-sectional Cohort
n=66 Participants
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)
|
Psoriatic Arthritis (PsA)
n=20 Participants
Patients with psoriatic arthritis (PsA), to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.
N=20 (actual)
|
Healthy Volunteers
n=58 Participants
Healthy individuals with no history of arthritis, to provide baseline samples of oral and intestinal microbiota for comparison with RA patients.
N=58 (actual)
|
|---|---|---|---|---|---|---|
|
Alteration of Microbiota, Alteration of T Cell Function/Activation
Change in oral/intestinal microbiota
|
4 participants
|
10 participants
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Alteration of Microbiota, Alteration of T Cell Function/Activation
Change in T cell function/activation
|
2 participants
|
6 participants
|
19 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: 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.
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).
Outcome measures
| Measure |
Rheumatoid Arthritis (RA) - Doxycycline
n=4 Participants
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
|
Rheumatoid Arthritis (RA) - Vancomycin
n=10 Participants
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
|
Rheumatoid Arthritis (RA) Randomized to no Treatment
n=19 Participants
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)
|
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)
|
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)
|
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)
|
|---|---|---|---|---|---|---|
|
Mean Units Change in DAS28 From Baseline to 6 Months
|
-1.3 units on a scale
Interval -1.7 to -0.4
|
-1.5 units on a scale
Interval -4.4 to -0.2
|
-2.5 units on a scale
Interval -3.9 to -0.9
|
—
|
—
|
—
|
Adverse Events
Rheumatoid Arthritis (RA) - Doxycycline
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Rheumatoid Arthritis (RA) - Vancomycin
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
RA, PsA, Healthy
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Rheumatoid Arthritis (RA) - Doxycycline
n=4 participants at risk
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
|
Rheumatoid Arthritis (RA) - Vancomycin
n=10 participants at risk
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
|
RA, PsA, Healthy
n=163 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
stomach pain/loose stools
|
0.00%
0/4 • Duration of the study, up to 6 months
|
10.0%
1/10 • Number of events 1 • Duration of the study, up to 6 months
|
0.00%
0/163 • Duration of the study, up to 6 months
|
Additional Information
Steven B. Abramson, MD
New York University School of Medicine
Phone: 212-263-8003
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place