Pulmonary HypertensionPhase 2/3ERAATHNCT01352065
Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
A Phase 2/3 study testing Bosentan and Ambrisentan in people with Pulmonary Hypertension, run by Center for Health Sciences, Serbia at 1 site in Serbia.
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. Read more about this study
- Who is it for?
- Ages 20 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Bosentan and Ambrisentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSerbia
- Study dates
- Jan 2011to May 2013
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- pregnancy
- use of hormonal contraceptives
- use of dietary supplement that contains any ergogenic agent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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
- Being tested
- Bosentan, Ambrisentan, Placebo
- Keywords
- Pharmacokinetics, Exercise performance, Athletes
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
tablet, 250 mg per day, twice per day, 8 weeks
AmbrisentanDrug
tablet, 10 mg per day, single per day, 8 weeks
PlaceboDrug
Tablet, 10 mg per day, single per day, 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| BOSENTAN | Experimental | Not described Receives: Drug: Bosentan |
| AMBRISENTAN | Experimental | Not described Receives: Drug: Ambrisentan |
| PLACEBO | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from Baseline in Maximal oxygen uptake at 8 weeks
Secondary outcomes (1)
Plasma concentration of bosentan
Measured: Regular sampling will be performed during administration at 0, 1, 2, 4, 6, and 8 weeks, and after 2 and 4 weeks post-administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2011 (estimated)
- Study startJan 2011
- Primary completionDec 2012
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Health Sciences, Serbia
- Sponsor type
- University, hospital or other
- Investigators
- Sergej M Ostojic, MD, PhD, Study director, Center for Health, Exercise and Sport Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01352065
- Sponsor's protocol ID
- CHS-ERA-2011
- Acronym
- ERAATH
- Status last verified
- May 2013
- First submitted
- 9 May 2011
- Last updated
- 8 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24342407
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Characterization and Detection of Prolonged Endothelin Receptors Antagonists Administration
- ClinicalTrials.gov ID
- NCT01352065
- Acronym / sponsor ID
- ERAATH / CHS-ERA-2011
- Conditions
- Pulmonary Hypertension
- Keywords
- Pharmacokinetics, Exercise performance, Athletes
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Center for Health Sciences, SerbiaUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 11 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BOSENTAN | Experimental | Drug: Bosentan |
| AMBRISENTAN | Experimental | Drug: Ambrisentan |
| PLACEBO | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 20 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- pregnancy
- use of hormonal contraceptives
- use of dietary supplement that contains any ergogenic agent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bosentantablet, 250 mg per day, twice per day, 8 weeks | Drug | BOSENTAN |
| Ambrisentantablet, 10 mg per day, single per day, 8 weeks | Drug | AMBRISENTAN |
| PlaceboTablet, 10 mg per day, single per day, 8 weeks | Drug | PLACEBO |
Primary outcome
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2013.
- Derived from this study: PubMed 24342407Ostojic 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sergej M Ostojic, MD, PhD study director
Center for Health, Exercise and Sport Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Bosentan and Ambrisentan in people with Pulmonary Hypertension, run by Center for Health Sciences, Serbia at 1 site in Serbia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal oxygen uptake (time frame: Change from Baseline in Maximal oxygen uptake at 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01352065, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2013.