Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration

Pulmonary Hypertension Clinical Trial

— ERAATH  

Official title:

Phase 3 Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01352065
• Other study ID #: CHS-ERA-2011
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 9, 2011
• Last updated: May 7, 2013
• Start date: January 2011
• Est. completion date: May 2013

Study information

• Verified date: May 2013
• Source: Center for Health, Exercise and Sport Sciences, Serbia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Serbia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: May 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 30 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Bosentan
tablet, 250 mg per day, twice per day, 8 weeks
• Ambrisentan
tablet, 10 mg per day, single per day, 8 weeks
• Placebo
Tablet, 10 mg per day, single per day, 8 weeks

Locations

Country	Name	City	State
Serbia	Center for Health, Exercise and Sport Sciences	Belgrade

Sponsors (1)

Lead Sponsor	Collaborator
Center for Health, Exercise and Sport Sciences, Serbia

Country where clinical trial is conducted

Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal oxygen uptake	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.	Change from Baseline in Maximal oxygen uptake at 8 weeks	No
Secondary	Plasma concentration of bosentan		Regular sampling will be performed during administration at 0, 1, 2, 4, 6, and 8 weeks, and after 2 and 4 weeks post-administration	Yes

External Links

•   Project info page