The ELSA trial: single versus combinatory effects of non-prohibited beta-2 agonists on skeletal muscle metabolism, cardio-pulmonary function and endurance performance-study protocol for a randomized 4-way balanced cross-over trial

• Published in: Current controlled trials in cardiovascular medicine Vol. 22; no. 1; pp. 903 - 10
• Main Authors: Zügel, Martina, Bizjak, Daniel A, Nussbaumer, Dorle, Winkert, Kay, Takabayashi, Kensuke, Kirsten, Johannes, Washington, Mickel, Treff, Gunnar, Dreyhaupt, Jens, Steeb, Luise, Diel, Patrick, Parr, Maria Kristina, Steinacker, Jürgen M, Persch, Hasema
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.12.2021; BioMed Central; BMC
• Subjects: Administration, Inhalation; Agonists (Biochemistry); Albuterol; Anti-doping; Asthma; Asthma sprays; Beta-2 agonists; Cardiopulmonary system; Cardiovascular system; Comparative analysis; Consent; Cross-Over Studies; Drug dosages; Drug stores; Electrocardiography; Endurance performance; Exercise; Health aspects; Hospitals; Humans; Inhalers; Metabolism; Muscle contraction; Muscle, Skeletal; Musculoskeletal system; Pharmacy; Physical Endurance; Physiological aspects; Randomized Controlled Trials as Topic; Respiratory organs; Study Protocol; Testing; Urine; Germany; Skeletal muscle/blood biomarkers; Anti-doping; Exercise; Cardiopulmonary function; Endurance performance; Ergogenic effects; Randomized controlled trial; Asthma sprays; Beta-2 agonists; Asthma; WADA
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-021-05862-w

Asthma 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. The 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. This 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. The 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 ).