Randomized, Double-Blind, Placebo-Controlled Trial of ID-CBT5101, a Tyndallized Clostridium butyricum Postbiotic, in Adults with Mild-to-Moderate Knee Osteoarthritis

Osteoarthritis (OA) is a common cause of chronic pain and functional impairment in older adults. Evidence suggests a gut-joint axis, where gut dysbiosis and systemic low-grade inflammation may contribute to OA pathogenesis. Postbiotics, which are non-viable microbial products such as heat-killed bacteria, have been proposed as safe and stable alternatives to live probiotics. ID-CBT5101, a tyndallized Clostridium butyricum preparation, reduced inflammation and preserved cartilage in a rat OA model. We conducted a 12-week randomized, double-blind, placebo-controlled trial to assess ID-CBT5101 safety and efficacy in adults with mild-to-moderate knee OA. Ninety-six participants were randomized to receive either ID-CBT5101 (1.0 × 10¹⁰ CFU-equivalents/day) or placebo. The primary endpoint was the change from baseline in walking pain on a 100-mm visual analog scale (VAS). Secondary outcomes included WOMAC, Korean Knee Score (KKS), patient global assessment, and serum biomarkers. Both groups showed significant within-group improvements in VAS, WOMAC, and KKS over 12 weeks. However, no significant differences were observed between groups for any clinical endpoint. Serum interleukin-6 (IL-6), cartilage oligomeric matrix protein (COMP), prostaglandin E₂ (PGE₂), leukotriene B₄ (LTB₄), transforming growth factor-β (TGF-β), and high-sensitivity C-reactive protein (hs-CRP) showed no consistent changes favoring ID-CBT5101. Safety profiles were comparable between groups, with no treatment-related adverse events. ID-CBT5101 was safe and well-tolerated, but it did not demonstrate significant clinical efficacy compared with placebo.