Allopurinol in Functional Impairment (ALFIE) Trial: 'Improving Muscle Strength'

Sarcopenia is defined as the presence of low muscle mass and either decreased muscle strength or function. It is increasingly becoming a significant cause of frailty, loss of independence and physical disability in ageing western populations. Recent experimental evidence has revealed that skeletal muscle is particularly susceptible to damaging molecules that result in oxidative stress and that oxidative stress plays a prominent role in the development and progression of sarcopenia. The investigators have previously shown that the xanthine oxidase inhibitor allopurinol is able to abolish vascular oxidative stress and improve endothelial function in cohorts such as optimally treated chronic heart failure and chronic kidney disease. Recently, the investigators have also shown that allopurinol improves exercise tolerance and time to ST-depression in optimally treated coronary artery disease, suggesting that allopurinol could also exert its effects through ATP and/or oxygen sparing mechanisms. Therefore, we propose a randomised double blind placebo-controlled parallel group trial of allopurinol in patients with primary sarcopenia using MR-spectroscopy and Flow Mediated Dilatation to investigate the possible mechanisms that underlie this exciting possibility

PCr repletion,Post-exercise muscle perfusion via arterial spin labelling (ASL) Pi/PCr ratio (a measure of ADP levels) Change in muscle volume (as measured by cross-sectional area on MR obtained during perfusion mapping)

Inclusion Criteria: Age 65 and over 6-Minute Walk Distance <400m Exclusion Criteria: Documented history of peripheral arterial disease. Pre-existing diagnosis of severe heart failure (LVEF<35%). Malignancy under active treatment (excluding basal cell carcinoma). Severe COPD (Physician diagnosis). Intolerance to allopurinol. Individuals with Active Acute Gout currently taking allopurinol; or those who have stopped taking allopurinol ≤1month previously for this condition. On long term high dose steroids (eq. Prednisolone>10mg/day due to risk of steroid induced myopathy and osteoporosis). Immobility that would render the patient incapable of doing the Short Physical Performance Battery Test (SPPB) or 6MWT. Patients who have participated in any other clinical drug trial within the previous 30 days will be excluded. Cognitive impairment precluding informed consent. Any other considered by a study physician to be inappropriate for inclusion.