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
  Purpose

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 Intervention Phase
Pulmonary Hypertension
Drug: Bosentan
Drug: Ambrisentan
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Phase 3 Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration

Resource links provided by NLM:


Further study details as provided by Center for Health, Exercise and Sport Sciences, Serbia:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 30
Study Start Date: January 2011
Study Completion Date: May 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   20 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352065

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

Additional Information:
No publications provided by Center for Health, Exercise and Sport Sciences, Serbia

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Center for Health, Exercise and Sport Sciences, Serbia
ClinicalTrials.gov Identifier: NCT01352065     History of Changes
Other Study ID Numbers: CHS-ERA-2011
Study First Received: May 9, 2011
Last Updated: May 7, 2013
Health Authority: Serbia: Ethics Committee

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

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014