Background Osteoarthritis (OA) accounts for more than a third of chronic moderate to severe pain in the UK. Sulforaphane (SFN) is a naturally occurring phytochemical derived from eating cruciferous vegetables, particularly broccoli. It has several biological activities that promote health, including anti-inflammatory properties. SFN has a potential role in limiting pain and cartilage destruction in OA.

Objectives In a two centre, placebo-controlled, double-blind, two-arm parallel, RCT, proof of principle study with a primary outcome we evaluated whether dietary SFN (from consumption of broccoli) improves pain in participants with knee OA. Secondary objectives were to determine whether food containing SFN improves knee function, and the feasibility of the study design for an appropriately powered trial.

Methods Participants with symptomatic and radiographic knee OA were recruited from regions of Norfolk and Leeds in the UK, were over 50 years of age with moderate to severe knee pain (at least 4 on 0-10 numeric rating scale), and radiological evidence of OA (Kellgren-Lawrence score 2-3). The intervention was a sensory-matched soup. Patients received either the intervention soup (300g high glucoraphanin soup (containing broccoli, and base vegetables)) or placebo soup (300g no glucoraphanin soup (base vegetables only)), once daily on 4 days per week. The study duration was 12 weeks with follow-up visits at 6 and 12 weeks. Knee pain and function outcome measures were obtained using WOMAC, an 11-point NRS, the ICOAP questionnaire and use of rescue analgesics/NSAIDS. Creatinine, metabolites of glucoraphanin, matrix metalloproteinase-3 and C-reactive protein were measured in plasma or 24-hour urine samples.

Results Recruitment was severely curtailed due to the Covid-19 pandemic. In total n= 37 consented and n= 24 met screening criteria with one drop-out at week 12 (control n=17 and intervention n= 7), the recruitment aim was n= 64. Control group was 43% female, and mean age was 70.14 yrs [7.69 SD] (control), and 61.88 yrs [8.58 SD] (intervention). Mean BMI was 26.4[2.91 SD] (control) and 28.2[4.68 SD] (intervention). The intervention resulted in a trend towards a decrease in pain scores for each subscale of WOMAC, ICOAP and NRS measures: total WOMAC median difference from baseline (9.65 [CI:-0.78,20.09]), ICOAP constant (wk 12, 4.83 [CI: -1.99,11.64]) and intermittent pain (wk 12, 2.96 [CI: -0.31,6.24]), NRS overall pain (wk 12, 1.86 [CI: 0.13,3.58]), while a trend for increased satisfaction for knee function (wk12, -1.55 [CI: -3.55,0.44]) was also observed for this group. No change in rescue analgesics/NSAIDS for knee pain was seen in either group. Metabolites of glucoraphanin were detected in plasma and urine samples in the intervention group. Study compliance and intervention adherence was high (>70%-100%) while acceptability for randomisation was 100%.

Conclusion Patient acceptability, adherence and retention was high and biomarkers and metabolites objectively confirming compliance with the intervention were detected. In this study, although underpowered to observe significant differences for pain, improving trends over time were observed across a range of clinical pain measures including the primary outcome, where the CI encompassed the minimal clinically important difference, requisite for progress to full trial. Given COVID impact on recruitment, the pilot achieved its aims, and we conclude that the intervention was feasible, and a full trial is justified.

Acknowledgements Our thanks to the study participants, study team, research nurses, and doctors; Fiona Brudenell-Straw, Lisa Cook, Lizzy Daniel, Asim Ghouri, Robert Hindmarsh, Kiran Khokar, Teja Kodali, Angela Nauth, Iraklis Papageorgiou, Tracey Swingler, Rabia Thompson, Nicola Ward, and Celia Whitehouse, and Trial committee Simon Donell (Independent Chair), Sam Norton (Independent Biostatistician) and Trish Phillips (Independent member) for their tenacity and team spirit throughout such an unprecedented time. This work is supported by grants from Versus Arthritis and Action Arthritis.

Disclosure of Interests Rose Davidson: None declared, Laura Watts: None declared, Gemma Beasy: None declared, Shikha Saha: None declared, Paul Kroon: None declared, Aedin Cassidy: None declared, Allan Clark: None declared, William Fraser Speakers bureau: Roche, Incstar/Diasorin, IDS, Sanofi, Siemens, Menarini, Abbott, Entera Bio, NPS pharmaceuticals and Alexis, Consultant of: Roche, Incstar/Diasorin, IDS, Sanofi, Siemens, Menarini, Abbott, Entera Bio, NPS pharmaceuticals and Alexis, Grant/research support from: Roche, Incstar/Diasorin, IDS, Sanofi, Siemens, Menarini, Abbott, Entera Bio, NPS pharmaceuticals and Alexis., Iain McNamara: None declared, Sarah Kingsbury: None declared, Philip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, AstraZeneca, Biosplice, BMS, Eli Lilly, Galapagos, Genascence, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Stryker, and UCB, Ian Clark: None declared, Alex MacGregor: None declared.