Effectiveness of Sustained Release Calcium Butyrate on the microbiome and clinical burden in osteoarthritis of the hand: A proof-of-concept placebo-controlled randomized trial

Abstract

OBJECTIVE: This study primarily assessed effects of Sustained Release Calcium Butyrate (SRCaBu) on gut microbiome composition and function in hand OA patients. Secondary objectives included its impact on hand pain and function, markers of intestinal permeability, systemic inflammation, and safety. METHOD: A participants, researchers, and pharmacy assistants blinded, randomized, placebo-controlled proof-of-concept trial compared 600 mg daily dose SRCaBu with placebo over 4-5 weeks. The primary domain was microbiome composition and function, assessed via fecal 16S rRNA gene- and metagenome sequencing, and short-chain fatty acid analysis. Secondary outcomes included parameters for intestinal barrier function, clinical outcomes and adverse events. Primary analyses followed the per-protocol principle. RESULTS: 35 participants (mean age 62.5±6.9 years, 82% female) were randomized to SRCaBu (n=18) or placebo (n=17). Two SRCaBu participants discontinued treatment for pre-existing liver impairment and need for pain medication. SRCaBu tended to reduce the relative abundance of Streptococcus (regression coefficient:-0.67, 95%CI:-1.46,0.13) and Faecalibacterium -0.38(-0.83,0.07), increase fecal acetate (median between-group difference: 9.5, [IQR]: [-3.5,22.5]), and was inversely associated with microbial LPS biosynthesis- and virulence genes. SRCaBu increased toxin-related genes, primarily from beneficial Blautia species, without association to pathogenicity. SRCaBu did not significantly affect biomarkers of intestinal permeability, inflammation, or clinical outcomes. Adverse events were mild and comparable between groups. CONCLUSION: Our study yielded indicative findings that SRCaBu supports microbiome health in patient with hand OA by improving compositional and functional characteristics of the microbiome. Although the treatment was well tolerated, effects on serum markers for intestinal barrier function and systemic inflammation, and clinical symptoms remained unclear. TRIAL REGISTER: 2020-001071-33 / NL73382.091.21.