Efficacy and safety of an oral complementary medicine combination in people with symptomatic knee osteoarthritis: Protocol for the double-blind, randomized, placebo-controlled ATLAS trial

Objective: To investigate the efficacy and safety of an oral complementary medicine combination formulation relative to placebo, on changes in pain intensity from baseline to week 12, in people with knee osteoarthritis (OA). Design: A placebo-controlled, double-blind, two-arm, superiority, phase II, Randomized Controlled Trial (RCT) (ACTRN12623000380695). We will recruit 82 participants (similar to 41 per arm), aged >= 40 years, with a clinical diagnosis of symptomatic knee OA and radiographic change on x-ray (Kellgren-Lawrence Grade >= 2). Participants will be randomly allocated to receive either a complementary medicine formulation containing a daily dose of Boswellia serrata extract (Boswellin (R) Super, 250 mg/day), pine bark extract (Fenoprolic (TM) 70 Organic 100 mg/day), curcumin (500 mg/day), piperine (5 mg/day), and methylsulfonylmethane (MSM, 1500 mg/day), or placebo, for 12-weeks. The primary endpoint will be change from baseline in average knee pain intensity at 12-weeks (visual analogue scale). Secondary endpoints will include change in knee pain from baseline to 12-weeks in the Knee Injury and Osteoarthritis Outcome Score (KOOS), global assessment of disease activity, global rating of change, and health-related quality of life (AQoL-8D). Ethics and dissemination: This protocol has been approved by the University of Sydney Human Research Ethics Committee (#2021/877). Dissemination will occur through lay summaries, infographics, conference abstracts, oral presentations, theses, and scientific publications. Conclusion: This RCT will provide credible evidence about the efficacy and safety of this complementary medicine combination and inform updates to international clinical practice standards on the use of complementary medicines in the management of symptomatic knee OA.