Clinical trial NCT01352065: Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
Official title: Phase 3 Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pulmonary Hypertension
Keywords: Pharmacokinetics
Exercise performance
Athletes
Lead sponsor: Center for Health Sciences, Serbia
Sponsor class: OTHER
First posted: 2011-05-11
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Endothelin receptors antagonists (ERA), such as bosentan and ambrisentan, are a class of vasoactive drugs that have been developed for the treatment of pulmonary arterial hypertension. It has been anecdotally reported that ERA is frequently used among top-level athletes to counteract exercise-induced rise in pulmonary vascular pressures and increase exercise performance. Yet, the effects of ERA on exercise capacity in healthy humans are puzzling, with the drugs not included in the current Prohibited List, since the ergogenic potential is yet to be fully understood and determined. Furthermore, the urinary excretion of ERA metabolites following administration has not been studied systematically at rest and during exercise in athletes, as a way to detect its intake if performance-enhancing potential is confirmed. In the planned study ERA will be administered in newly approved doses for 8 weeks in order to assess the presumed doping potential for both male and female athletes, and to monitor serum and urinary ERA excretion dynamics after single- and multiple-dose administration. The possible effects of prolonged ERA administration in higher doses on exercise performance may be relevant, if further confirmed, in terms of their possible fraudulent utilization to influence exercise performance in sports, raising the difficult question of whether, particularly in some circumstances, the ERA might be considered as prohibited substances in athletes.

Detailed description: Preliminary findings of our research group indicated that ERA enhances exercise performance (particularly aerobic) after 7-day intake of higher doses of non-selective ERA bosentan (doses used were approved for pulmonary arterial hypertension treatment). This is in part in accordance with results of previous research (Faoro et al. 2009), although authors administered regular single dose (62.5 mg) of bosentan in hypoxic healthy subjects. Our study should examine metabolic profiles of athletes after receiving significantly higher doses of two oral ERA as compared to previous research, along with assessment of ergogenic potential with 8 weeks of administration in placebo-control and randomized design. We expect that ERA will increase time to exhaustion during endurance test, increase the maximal oxygen uptake and rate of ultra-short term heart rate recovery after exercise, and affecting blood and urine cortisol, testosterone and dehydroepiandrosterone following administration. Moreover, we will clearly evaluate 24-h pharmacokinetic profile of ERA in blood and urine and collect data for concentration-time profiles of ERA and main active metabolites, in aim to provide more rationale basis for identification and detection for doping control.

Eligibility criteria: Inclusion Criteria:

* male and female volunteers
* experienced in athletic training (\> 5 years of experience)
* aged 20 to 30 years
* free from musculoskeletal dysfunctions
* free from metabolic and heart diseases

Exclusion Criteria:

* pregnancy
* use of hormonal contraceptives
* use of dietary supplement that contains any ergogenic agent

Primary outcomes:
measure: Maximal oxygen uptake
timeFrame: Change from Baseline in Maximal oxygen uptake at 8 weeks
Secondary outcomes:
measure: Plasma concentration of bosentan
timeFrame: Regular sampling will be performed during administration at 0, 1, 2, 4, 6, and 8 weeks, and after 2 and 4 weeks post-administration
Other outcomes:
Locations:
city: Belgrade
country: Serbia
facility: Center for Health, Exercise and Sport Sciences
Study officials:
affiliation: Center for Health, Exercise and Sport Sciences
name: Sergej M Ostojic, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Ostojic SM, Stojanovic M, Calleja-Gonzalez J, Olcina G, Sekulic D, Hoffman JR. Performance-enhancing effects of non-selective endothelin receptor antagonist. Int J Cardiol. 2014 Feb 1;171(2):294-7. doi: 10.1016/j.ijcard.2013.11.077. Epub 2013 Dec 4. No abstract available.