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Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration (ERAATH)

This study has been completed.
Sponsor:
Information provided by:
Center for Health, Exercise and Sport Sciences, Serbia
ClinicalTrials.gov Identifier:
NCT01352065
First received: May 9, 2011
Last updated: May 7, 2013
Last verified: May 2013

May 9, 2011
May 7, 2013
January 2011
December 2012   (final data collection date for primary outcome measure)
Maximal oxygen uptake [ Time Frame: Change from Baseline in Maximal oxygen uptake at 8 weeks ] [ Designated as safety issue: No ]
Maximal oxygen uptake is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise, which reflects the physical fitness of the individual.
Same as current
Complete list of historical versions of study NCT01352065 on ClinicalTrials.gov Archive Site
Plasma concentration of bosentan [ Time Frame: Regular sampling will be performed during administration at 0, 1, 2, 4, 6, and 8 weeks, and after 2 and 4 weeks post-administration ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
Phase 3 Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Pulmonary Hypertension
  • Drug: Bosentan
    tablet, 250 mg per day, twice per day, 8 weeks
  • Drug: Ambrisentan
    tablet, 10 mg per day, single per day, 8 weeks
  • Drug: Placebo
    Tablet, 10 mg per day, single per day, 8 weeks
  • Experimental: BOSENTAN
    Intervention: Drug: Bosentan
  • Experimental: AMBRISENTAN
    Intervention: Drug: Ambrisentan
  • Placebo Comparator: PLACEBO
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
May 2013
December 2012   (final data collection date for primary outcome measure)

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
Both
20 Years to 30 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Serbia
 
NCT01352065
CHS-ERA-2011
Yes
Center for Health, Exercise and Sport Sciences, Serbia
Center for Health, Exercise and Sport Sciences, Serbia
Not Provided
Study Director: Sergej M Ostojic, MD, PhD Center for Health, Exercise and Sport Sciences
Center for Health, Exercise and Sport Sciences, Serbia
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP