Remote ischaemic conditioning for fatigue after stroke (RICFAST): a pilot, single-blind, randomised, placebo-controlled trial

Post-stroke fatigue (PSF) affects up to 75% of stoke survivors at some stage after stroke. The precise mechanisms that underlie PSF are still being unravelled but it may develop due to changes in cortical excitability, inflammation, and impaired cellular energetics. It negatively impacts neurological recovery, return to work and quality of life (QoL). There are currently no well evidenced treatments. Remote ischaemic conditioning (RIC) is a novel treatment whereby brief and reversible episodes of ischaemia and reperfusion are applied to a limb. It may lead to alterations in inflammation, tissue perfusion and mitochondrial function, that theoretically counteract factors contributing to PSF. The primary aim of this thesis was to investigate the safety, acceptability, and feasibility of RIC to treat PSF by undertaking a single-centre, single-blind, pilot, randomised, placebo-controlled trial. Participants with PSF were randomised to RIC or sham control for 6 weeks and measures of fatigue, physical function, mood, and QoL were assessed at baseline, 6-weeks, 3-months, and 6-months. Mechanistic evaluation using cardiopulmonary exercise testing and 31Phosphorus-Magnetic Resonance Spectroscopy (31P-MRS) of peripheral muscles was also undertaken. RIC was safe, acceptable, and feasible for people with PSF. RIC appears to result in clinically meaningful improvements in fatigue that persisted beyond treatment cessation, independent to mood or functional state and was associated with increased walking distances. These changes may be associated with improvements in thresholds for efficient energy production (ventilatory anaerobic threshold). 31P-MRS suggested this may be driven by improvements in the energy producing capabilities of mitochondria (adenosine triphosphate content of muscle). We have demonstrated that RIC is a promising treatment strategy for patients with PSF that is low cost and widely implementable if found to be effective. It warrants further definitive investigation in larger studies.