This was a randomized, double-blind, placebo-controlled, parallel-design study of Bacillus coagulans GBI-30, 6086 LAB probiotic as an adjunctive therapy for the relief of symptoms of RA. The objective was to evaluate the effects of Bacillus coagulans GBI-30, 6086 on RA symptoms compared with placebo.
The treatment allocation scheme was generated and assigned by a third party who did not have direct patient contact. The treatment assignments were in sealed, tamper-proof, blinded envelopes and were handed out in sequential fashion according to a computer-generated randomization list. Study personnel did not have access to the randomization scheme or blinding process. Collected data were concealed in a pouch that remained unopened until all results were submitted.
This study was registered with the Australian New Zealand Clinical Trials Registry.
Forty-five adult men and women with symptoms of RA were included in the study. Sample size was determined by power analysis. Subjects were recruited by the primary investigator from his daily practice and follow-up visits were conducted at the practice.
Inclusion criteria included men and women with RA for at least 1 year and up to 80 years of age. The criteria for the diagnosis of RA included four or more of the following symptoms: 1) morning stiffness lasting at least 1 hour; 2) soft tissue swelling in 3 or more joint areas observed by a physician; 3) swelling of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling; 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. The first 4 criteria must have been present for at least 6 weeks for inclusion in the study.
The exclusion criteria were pregnancy, chronic inflammatory bowel disease, kidney disease, liver disease, exposure to > 10 mg/day of prednisolone, or treatment with other probiotic products.
Patients read and signed an approved consent form prior to enrollment in the study. The study protocol and test product(s) information were approved by an Institutional Review Board (IRB; Schulman Associates, Cincinnati, OH) prior to the beginning of the study.
Patients in each group underwent a baseline physical assessment and then were randomized in a double-blind manner to receive either placebo or 1 caplet of Bacillus coagulans GBI-30, 6086 (2 billion CFU) daily at approximately the same time each day, regardless of meals, for a period of 60 days. The probiotic preparation includes Bacillus coagulans GBI-30, 6086, green tea extract, methylsulfonylmethane, and vitamins and minerals (including vitamins A, B, C, D, E, folic acid, and selenium). The matching placebo contained microcrystalline cellulose. Adherence to the study protocol was determined by caplet count at each examination.
The 45 men and women enrolled in the study were randomly assigned to receive Bacillus coagulans GBI-30, 6086 or placebo once a day for 60 days. Patients were examined at the primary investigator's practice at baseline, at 30 days, and at 60 days to assess symptoms and measures of disease activity. Blood draws were performed at each visit. The primary outcome was change from baseline compared with the end of the study period obtained by the American College of Rheumatology (ACR)  criteria questionnaire and the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) . Outcomes were classified as "global" (sensitive to change in clinical trials) and "individual" (relatively insensitive to change in clinical trials). The global outcomes included patients' global assessment, pain assessment, and disability assessment, as well as physicians' global assessment, assessment of total painful joints out of 68 joints assessed, total swollen joints out of 66 joints assessed, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels from ACR and pain from the HAQ-DI. Individual outcomes were assessed based on hygiene (ability to wash and dry the body, take a tub bath, get on and off the toilet) and the ability to dress and groom, arise, eat, walk 2 miles, reach, grip, and participate in daily activities. Serious adverse events were reported directly to the sponsor and IRB by each investigator.
For each outcome, summary measures based on the change from baseline to 60 days were obtained for each group and group differences were tested. For global variables, each response was normalized (using Blom scores) and the difference (end minus baseline) was obtained to provide a change score. A Student's t test was performed to test for a difference in the mean change score between subjects randomized to Bacillus coagulans GBI-30, 6086 vs placebo. The effectiveness of the normalization was checked via the Shapiro-Wilk test for normality and the folded form F statistic to test for equality of group variances. For individual outcomes, due to their discrete nature, we utilized the binary indicator of a difference score of less than zero, indicating some improvement in the score for the item. Barnard's exact unconditional test was used to compare the proportions who improved in the Bacillus coagulans GBI-30, 6086 group vs placebo for each individual scale. Two-sided P < .05 was considered statistically significant. Ninety-five percent confidence intervals were computed for the group difference for each outcome. For continuous outcomes, confidence intervals for mean differences were obtained based on a t test for normalized scores. For binary outcomes, exact confidence intervals for the difference in proportions were computed.
Analyses were performed using SAS Version 8.0 (SAS System, SAS Institute, Cary, NC) and StatXact Version 4.0 (Cytel Software Corporation, Cambridge, MA).