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

Abstract

ObjectiveAssess whether treatment with probiotics improve gastrointestinal symptoms in patients with systemic sclerosis (SSc). MethodsIn 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® 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, T2) by an intention-to-treat approach. Stool samples at three time-points were subjected to 16S next generation sequencing. ResultsForty 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. ConclusionWhilst 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. Trial registration. Clinicaltrials.gov; NCT01804959