49EFFECT OF ALLOPURINOL ON SKELETAL MUSCLE PHOSPHOCREATINE RECOVERY RATE AND PHYSICAL FUNCTION IN OLDER PEOPLE WITH IMPAIRED PHYSICAL FUNCTION: A RANDOMISED CONTROLLED TRIAL

Abstract

Introduction: Allopurinol, commonly used for gout, has powerful antioxidant and oxygen-sparing effects, and also participates in purinergic signalling within muscle. These effects may be of importance in reversing functional deficits seen in ageing skeletal muscle. We therefore tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with exercise limitation. Methods: Randomised, parallel group, placebo controlled, double blind trial. We recruited participants aged 65 and over with baseline six minute walk distance of <400 m and no contraindications to MRI scanning. Participants were randomised to receive 600 mg oral allopurinol or matching placebo once daily for 20 weeks. Outcomes were measured at baseline and 20 weeks. The primary outcome was phosphocreatine recovery rate in the calf muscles after exercise to fatigue, measured using 31P magnetic resonance spectroscopy. Secondary outcomes included six minute walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function measured by flow-mediated brachial artery dilatation, and quality of life (EQ5D). Results: 124 participants were randomised, mean age 80 (SD 6) years. 59 (48%) were female, baseline six minute walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Adherence to allopurinol and placebo was excellent (93% vs 95%). 116/124 (94%) attended the 20 week visit. Allopurinol did not significantly improve phosphocreatine recovery rate (treatment effect 0.10 units [95%CI -0.07 to 0.27], p = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or the SPPB (treatment effect 0.0 [95%CI -0.5 to 0.5], p = 0.91). Allopurinol produce a modest improvement in six minute walk distance (treatment effect 25 m [95% 4 to 46, p = 0.02]). Adverse events were more frequent in the allopurinol group (121 vs 85). Conclusion: Allopurinol improved six-minute walk distance but not phosphocreatine recovery rate in older people with impaired physical function.