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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01352065
Recruitment Status : Completed
First Posted : May 11, 2011
Last Update Posted : May 8, 2013
Information provided by:
Center for Health, Exercise and Sport Sciences, Serbia

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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: Bosentan Drug: Ambrisentan Drug: Placebo Phase 2 Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Phase 3 Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
Study Start Date : January 2011
Actual Primary Completion Date : December 2012
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BOSENTAN Drug: Bosentan
tablet, 250 mg per day, twice per day, 8 weeks

Experimental: AMBRISENTAN Drug: Ambrisentan
tablet, 10 mg per day, single per day, 8 weeks

Placebo Comparator: PLACEBO Drug: Placebo
Tablet, 10 mg per day, single per day, 8 weeks

Primary Outcome Measures :
  1. Maximal oxygen uptake [ Time Frame: Change from Baseline in Maximal oxygen uptake at 8 weeks ]
    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.

Secondary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   20 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01352065

Center for Health, Exercise and Sport Sciences
Belgrade, Serbia, 11000
Sponsors and Collaborators
Center for Health, Exercise and Sport Sciences, Serbia
Study Director: Sergej M Ostojic, MD, PhD Center for Health, Exercise and Sport Sciences

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Center for Health, Exercise and Sport Sciences, Serbia Identifier: NCT01352065     History of Changes
Other Study ID Numbers: CHS-ERA-2011
First Posted: May 11, 2011    Key Record Dates
Last Update Posted: May 8, 2013
Last Verified: May 2013

Keywords provided by Center for Health, Exercise and Sport Sciences, Serbia:
Exercise performance

Additional relevant MeSH terms:
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Endothelin Receptor Antagonists
Antihypertensive Agents
Molecular Mechanisms of Pharmacological Action