Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials.

Exercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD) and, although multifactorial, it is largely caused by lower-limb muscle dysfunction. Research has shown that patients with severe to very severe COPD have significantly lower levels of muscle carnosine, which acts as a pH buffer and antioxidant. Beta-alanine (BA) supplementation has been shown to consistently elevate muscle carnosine in a variety of populations and may therefore improve exercise tolerance and lower-limb muscle function. The primary objective of the current studies is to assess the beneficial effects of BA supplementation in enhancing exercise tolerance on top of two types of exercise training (non-linear periodised exercise (NLPE) training or neuromuscular electrical stimulation (NMES)) in patients with COPD. Two randomised, double-blind, placebo-controlled trials have been designed. Patients will routinely receive either NLPE (BASE-TRAIN trial) or NMES (BASE-ELECTRIC trial) as part of standard exercise-based care during their 8-to-10 week pulmonary rehabilitation (PR) programme. A total of 222 patients with COPD (2×77 = 154 patients in the BASE-TRAIN trial and 2×34 = 68 patients in the BASE-ELECTRIC trial) will be recruited from two specialised PR centres in The Netherlands. For study purposes, patients will receive 3.2 g of oral BA supplementation or placebo per day. Exercise tolerance is the primary outcome, which will be assessed using the endurance shuttle walk test (BASE-TRAIN) or the constant work rate cycle test (BASE-ELECTRIC). Furthermore, quadriceps muscle strength and endurance, cognitive function, carnosine levels (in muscle), BA levels (in blood and muscle), markers of oxidative stress and inflammation (in blood, muscles and lungs), physical activity and quality of life will be measured. Both trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19). NTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC).

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Competing interests: FMEF reports research grants from AstraZeneca and Novartis, not related to the current projects, and personal fees for consultancies and lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and TEVA. EBdV reports personal fees for consultancies and lectures from Boehringer Ingelheim, Chiesi, Mylan, Novartis, Vivisol and TEVA, not related to the current projects. FNS reports speakers fees from AstraZeneca, Chiesi, Menarini, Mundipharma and Novartis; reports consultancy fees from GSK; and reports service on an advisory board for AstraZeneca, Chiesi, GSK and Novartis, all outside the submitted work. MH reports research grants from Bastide Medical, not related to the current project; personal fees from AstraZeneca for participation to scientific lectures; financial support for congress participation from SOS Oxygène, Eole Santé, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca; and hospitalities during local scientific meetings from ALK-Abelló, Actelion Pharmaceuticals France, Vifor Fresenius Medical Care Renal Pharma, Sanofi Aventis France, Novartis Pharma, LVL Medical Sud, Chiesi, SOS Oxygene Mediterranee. MAS reports a research grant from Netherlands Lung Foundation (grant number 5.1.18.232) for the described BASE-TRAIN and BASE-ELECTRIC study. Moreover, MAS reports other grants from Netherlands Lung Foundation, grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, and a grant from Stichting Astma Bestrijding, all outside the submitted work.