Abstract
BackgroundAsthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor (beta-2) agonists use. Nevertheless, there are data on dose-dependent ergogenic effects of beta-2 agonists suggesting increased muscle strength, endurance and neuromuscular performance. Therefore, most beta-2 agonists belong to the World Anti Doping Agency (WADA) list of prohibited substances and it is tempting to speculate that illegitimate use of beta-2 agonists might be a common practice to boost performance in competitive sports. It is currently unknown whether or not inhaled beta-2 agonists enhance performance by stimulatory effects in skeletal and cardiac muscle.MethodsThe ELSA trial is a double-blinded, placebo-controlled, randomized, balanced, four-way cross-over study. Study participants (n=24, 12 ♀, 12 ♂) complete four study arms (i.e. periods with treatment A, placebo; B, salbutamol; C, formoterol; D, formoterol + salbutamol) in random order after an initial preliminary testing session. Participants inhale the study medication 20 min before the 10-min time trial (TT; exercise performance test), where participants cycle 10 min at the highest possible workload. Cardiac output is measured continuously. A skeletal muscle biopsy is collected 3 h after the TT. Study endpoints include measures of skeletal muscle expression of nuclear receptors, hormones and cytokine levels, urinary and plasma concentrations of salbutamol and formoterol, circulating cardiac markers, cardiopulmonary function and exercise performance (average power and peak power during the TT). Blood and urine are collected and respiratory testing is performed 24 h post TT.Summary/conclusionsThis clinical trial evaluates the potential performance-enhancing effects of non-prohibited, not medically indicated inhaled short- and long-acting beta-2 agonists on skeletal muscle gene expression, endocrine regulation, cardiac biomarkers, cardiopulmonary function and acute endurance exercise performance. These data will be used by WADA to adapt the annually published list of prohibited substances (WADA 2021) and will be published in scientific journals.Trial registrationThe trial is registered at the European Clinical Trials Database (Eudra CT) with the number: 2015-005598-19 as well as at the German register for clinical studies (DRKS number 00010574).
Highlights
Asthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor agonists use
The outcome measures will focus on skeletal muscle metabolism, endocrine regulation, cardiopulmonary function and endurance performance (Fig. 1)
Hormonal targets To investigate the effects of beta-2 agonist treatment on the endocrine system in male and female study participants, variables for muscular growth, cytokine activity, stress responses and hormonal activity will be determined in blood before treatment and 0.25 h, 3 h and 24 h post-exercise using ELISA assays
Summary
Study design This is a prospective, monocentric, randomized, sexstratified, double-blinded, placebo-controlled, balanced, four-way cross-over trial. If participants pass the medical examination and fulfil none of the exclusion criteria (complete list in supplementary information, Additional file 1), they are randomly allocated to start in one of the four experimental treatments (Fig. 1—A, placebo; B, salbutamol; C, formoterol; or D, salbutamol + formoterol) after informed consent is obtained All these actions are carried out at one trial site (Division of Sports and Rehabilitation Medicine, Department of Internal Medicine II, University Hospital Ulm, Germany). At the four experimental study visits, blood (2 × 2.7 ml EDTA Plasma, 2 × 7.5 ml Serum, 1 × 9 ml Lithium-Heparin) and urine samples (30 ml) are collected prior to the inhalation of the study medication and 15 min, 3 h and 24 h post-exercise. Urinary and plasma beta-2 agonist testing Urine (30 ml) is collected before inhalation and at 15 min, 3 h and 24 h post-exercise (4 samples per study arm). Details of the statistical analyses and possible changes will be included in the statistical analysis plan (SAP, available in supplementary information, Additional file 2)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
