A double-blind randomized placebo-controlled trial of probiotics in systemic sclerosis associated gastrointestinal disease.

Objective: Assess whether treatment with probiotics improve gastrointestinal symptoms in patients with systemic sclerosis (SSc). Methods: In this double-blind randomized placebo-controlled parallel-group phase II trial, SSc subjects with total score >= 0.1 on a validated SSc-specific gastrointestinal tract (GIT) questionnaire were randomized (1:1) to receive 60 days of high dose multi-strain probiotics (Vivomixx (R) 1800 billion units/day) or identical placebo, followed by an additional 60 days of probiotics in both groups. Between group differences in GIT score change were assessed after 60 days (primary outcome, time-point T1) and 120 days (secondary outcome, time-point, 12) by an intention-to-treat approach. Stool samples at three time-points were subjected to 16S next generation sequencing. Results: Forty subjects were randomized to placebo-probiotics (n = 21) or probiotics-probiotics (n = 19). At T1, no significant improvement was observed between the two groups, reported as mean +/- SE for total GIT score (placebo 0.14 0.06 versus probiotics 0.13 +/- 0.07; p = 0.85) or its subdomains. At T2, whilst there was no significant improvement in total GIT score (placebo-probiotics -0.05 +/- 0.06; probiotics-probiotics -0.18 +/- 0.07; p = 0.14), there was significant improvement of GIT-reflux in the probiotic group (-0.22 +/- 0.05 versus placebo-probiotics 0.05 +/- 0.07; p = 0.004). Subjects on probiotics exhibited increasing stool microbiota alpha diversity compared to the placebo-probiotics group. Adverse events (AEs) were mild, with similar proportion of subjects with AEs and serious AEs in both groups. Conclusion: Whilst there was no clear improvement in overall GI symptoms after 60 days, we observed significantly improved GI reflux after 120 days of probiotics. The trial confirmed safety of multi-strain probiotics in SSc patients. (C) 2019 The Authors. Published by Elsevier Inc.