Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration

NCT ID: NCT01352065

Last Updated: 2013-05-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2013-05-31

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.

Conditions

Pulmonary Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

BOSENTAN

Group Type: EXPERIMENTAL

Bosentan

Intervention Type: DRUG

tablet, 250 mg per day, twice per day, 8 weeks

AMBRISENTAN

Group Type: EXPERIMENTAL

Ambrisentan

Intervention Type: DRUG

tablet, 10 mg per day, single per day, 8 weeks

PLACEBO

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablet, 10 mg per day, single per day, 8 weeks

Interventions

Bosentan

tablet, 250 mg per day, twice per day, 8 weeks

Intervention Type: DRUG

Ambrisentan

tablet, 10 mg per day, single per day, 8 weeks

Intervention Type: DRUG

Placebo

Tablet, 10 mg per day, single per day, 8 weeks

Intervention Type: DRUG

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Center for Health Sciences, Serbia

OTHER

Sponsor Role: lead

Responsible Party

Center for Health, Exercise and Sport Sciences, Serbia

Principal Investigators

Sergej M Ostojic, MD, PhD

Role: STUDY_DIRECTOR

Center for Health, Exercise and Sport Sciences

Locations

Center for Health, Exercise and Sport Sciences

Belgrade, , Serbia

Countries

Serbia

References

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.

Reference Type: DERIVED

PMID: 24342407 (View on PubMed)

Other Identifiers

CHS-ERA-2011

Identifier Type: -

Identifier Source: org_study_id