Pulmonary Arterial HypertensionEarly Phase 1NCT01100736
Role of Endothelin-A (ETA) and Endothelin-B (ETB) Receptors in the Vasodilatory Response to Endothelin-3 (ET-3)
A Early Phase 1 study testing Bosentan, Sitaxsentan and Endothelin-3 in people with Pulmonary Arterial Hypertension and Vasodilation, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
Endothelin-1 (ET-1) has been linked to a number of conditions including pulmonary arterial hypertension (PAH). ET-1 acts via 2 receptors, ETA and ETB. The ET-1 receptor blockers bosentan and sitaxsentan have been shown to be beneficial in patients with PAH. Bosentan blocks both ETA and ETB receptors. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension, Vasodilation, Vasoconstriction
- What is being tested?
- Bosentan, Sitaxsentan and Endothelin-3
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2009to Jan 2010
- Phase
- Early Phase 1
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men and post-menopausal women
- Age 18-70 years
- BMI 18-35 kg/m2
Who cannot join
- Are mentally or legally incapacitated
- Have donated blood within the last 4 weeks
- Have a history of past or present drug or alcohol abuse
- Have participated in another clinical trial within 1 month
- Are considered to be at a high risk of HIV or Hepatitis B
- Are taking routine medicines
- Are women taking hormone replacement therapy
- Have significant medical or psychiatric illness
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Centre, Western General Hospital
Edinburgh, Scotland, EH4 2XU
About this study
Official title: Characterisation of the Role of ETA and ETB Receptors in Regulating Plasma ET-1 and the Vasodilator Response to ET-3 in Man
Endothelin-1 (ET-1) has been linked to a number of conditions including pulmonary arterial hypertension (PAH). ET-1 acts via 2 receptors, ETA and ETB. The ET-1 receptor blockers bosentan and sitaxsentan have been shown to be beneficial in patients with PAH. Bosentan blocks both ETA and ETB receptors. Sitaxsentan selectively blocks ETA receptors. Theoretically, selective ETA blockade may be associated with greater vasodilation and clearance of ET-1 by leaving the ETB receptor unblocked. This has not been directly studied in humans.
We aim to investigate the endothelial ETB-mediated vascular responses between bosentan and sitaxsentan by using a ETB selective agonist (ET-3). We hypothesise that at clinically relevant doses:
- Bosentan will show evidence of ETB receptor blockade compared to sitaxsentan and placebo.
- These effects will be confirmed by 2 functional markers of ETB receptor antagonism: plasma ET-1 (a very sensitive, but not necessarily clinically relevant marker), and the forearm vasodilator response to ET-3.
- Being tested
- Bosentan, Sitaxsentan, Placebo, Endothelin-3
- Keywords
- Forearm Blood Flow, Vasodilation, Vasoconstriction, Endothelin System, Endothelin-1, Endothelin-3, Endothelin antagonists, Bosentan, Sitaxsentan, Endothelin, Regional Blood Flow
- Medical subject headings
- Pulmonary Arterial Hypertension, Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Also called Tracleer
Bosentan 125mg tablets, orally, twice daily for 7 days
SitaxsentanDrug
Also called Thelin
Sitaxsentan 100mg tablets, orally, once daily for 7 days
PlaceboDrug
Placebo tablets taken twice daily, orally, for 7 days (placebo arm) or once daily for 7 days (sitaxsentan arm)
Endothelin-3Biological
5 minute local intra-arterial infusion of endothelin-3 at a rate of rate of 60 pmol/min, during forearm blood flow studies
| Study group | Role | What they receive |
|---|---|---|
| Bosentan | Experimental | Bosentan 125mg twice daily will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of bosentan therapy Receives: Drug: Bosentan; Biological: Endothelin-3 |
| Sitaxsentan | Experimental | Sitaxsentan 100mg once daily + placebo tablet will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of sitaxsentan therapy Receives: Drug: Sitaxsentan; Drug: Placebo; Biological: Endothelin-3 |
| Placebo | Placebo comparator | Placebo tablet twice daily will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of placebo therapy Receives: Drug: Placebo; Biological: Endothelin-3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma ET-1 after 7-day administration of bosentan, sitaxsentan and placebo
Measured: 7 days
Responses to ET-3 (maximum vasodilation after ET-3 administration and area under the curve of vasodilation) after bosentan compared with the results from sitaxsentan and placebo.
Measured: 60 mins
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2010 (estimated)
- Study startJan 2009
- Primary completionSep 2009
- Study completionJan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Encysive Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01100736
- Sponsor's protocol ID
- 2008/W/CRC/01
- Other IDs
- 08/S1102/1
- Status last verified
- Jul 2015
- First submitted
- 30 Mar 2010
- Last updated
- 21 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterisation of the Role of ETA and ETB Receptors in Regulating Plasma ET-1 and the Vasodilator Response to ET-3 in Man
- ClinicalTrials.gov ID
- NCT01100736
- Acronym / sponsor ID
- 2008/W/CRC/01
- Keywords
- Forearm Blood Flow, Vasodilation, Vasoconstriction, Endothelin System, Endothelin-1, Endothelin-3, Endothelin antagonists, Bosentan
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- Encysive Pharmaceuticals
- Study start
- Jan 2009
- Primary completion
- Sep 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 9 Apr 2010 (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-1 (ET-1) has been linked to a number of conditions including pulmonary arterial hypertension (PAH). ET-1 acts via 2 receptors, ETA and ETB. The ET-1 receptor blockers bosentan and sitaxsentan have been shown to be beneficial in patients with PAH. Bosentan blocks both ETA and ETB receptors. Sitaxsentan selectively blocks ETA receptors. Theoretically, selective ETA blockade may be associated with greater vasodilation and clearance of ET-1 by leaving the ETB receptor unblocked. This has not been directly studied in humans.
We aim to investigate the endothelial ETB-mediated vascular responses between bosentan and sitaxsentan by using a ETB selective agonist (ET-3). We hypothesise that at clinically relevant doses:
- Bosentan will show evidence of ETB receptor blockade compared to sitaxsentan and placebo.
- These effects will be confirmed by 2 functional markers of ETB receptor antagonism: plasma ET-1 (a very sensitive, but not necessarily clinically relevant marker), and the forearm vasodilator response to ET-3.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bosentan | Experimental | Drug: Bosentan, Biological: Endothelin-3Bosentan 125mg twice daily will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of bosentan therapy |
| Sitaxsentan | Experimental | Drug: Sitaxsentan, Drug: Placebo, Biological: Endothelin-3Sitaxsentan 100mg once daily + placebo tablet will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of sitaxsentan therapy |
| Placebo | Placebo comparator | Drug: Placebo, Biological: Endothelin-3Placebo tablet twice daily will be taken for 7 days, before ET-1 plasma sample taken. ET-3 infusion (5mins) and associated forearm blood flow study (60 mins) will also occur after 7 days of placebo therapy |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy men and post-menopausal women
- Age 18-70 years
- BMI 18-35 kg/m2
Key exclusion criteria (8 listed)
- Are mentally or legally incapacitated
- Have donated blood within the last 4 weeks
- Have a history of past or present drug or alcohol abuse
- Have participated in another clinical trial within 1 month
- Are considered to be at a high risk of HIV or Hepatitis B
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 |
|---|---|---|
| BosentanAlso: TracleerBosentan 125mg tablets, orally, twice daily for 7 days | Drug | Bosentan |
| SitaxsentanAlso: ThelinSitaxsentan 100mg tablets, orally, once daily for 7 days | Drug | Sitaxsentan |
| PlaceboPlacebo tablets taken twice daily, orally, for 7 days (placebo arm) or once daily for 7 days (sitaxsentan arm) | Drug | Placebo, Sitaxsentan |
| Endothelin-35 minute local intra-arterial infusion of endothelin-3 at a rate of rate of 60 pmol/min, during forearm blood flow studies | Biological | Bosentan, Placebo, Sitaxsentan |
Primary outcome
Plasma ET-1 after 7-day administration of bosentan, sitaxsentan and placebo
Time frame: 7 days
Responses to ET-3 (maximum vasodilation after ET-3 administration and area under the curve of vasodilation) after bosentan compared with the results from sitaxsentan and placebo.
Time frame: 60 mins
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 21 Jul 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Bosentan, Sitaxsentan and Endothelin-3 in people with Pulmonary Arterial Hypertension and Vasodilation, run by University of Edinburgh at 1 site in United Kingdom.
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 3 inclusion and 8 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 21 Jul 2015. 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 United Kingdom. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Plasma ET-1 after 7-day administration of bosentan, sitaxsentan and placebo (time frame: 7 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Jul 2015.