AsthmaPhase 2NCT01617746
Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma
A Phase 2 study testing Ambrisentan and Bosentan in people with Asthma, run by University of Glasgow at 1 site in United Kingdom.
Trial summary
The purpose of this study will be to determine if blockade of endothelin 1 signalling via endothelin receptor A using ambrisentan or dual blockade (A\&B) via bosentan can provide protection against methacholine induced bronchoconstriction in asthma. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Asthma
- What is being tested?
- Ambrisentan and Bosentan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2012to Dec 2015
- Phase
- Phase 2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Physician diagnosis of asthma confirmed objectively by airway hyperactivity to methacholine (as determined by a ≥ 20% drop in FEV at a methacholine dose of ≤ 8mg/ml after β-agonist withdrawal as per ATS guidelines)
- Age range 18-60 years
- FEV1 ≥ 60% predicted
- Duration of asthma > 6 months and on stable medication for 4 weeks
- Prescribed and compliant with inhaled corticosteroid up to a maximum of 2000mcg beclomethasone or equivalent
- No history of previous regular smoking and current non-smoker
Who cannot join
- Unstable asthma; defined as the presence of 1 or more of the following events in the month prior to study [Emergency/'out of hours' visit to GP for asthma exacerbation; GP visit to patient at home for asthma exacerbation or A \& E/hospital admission for asthma exacerbation]
- Treatment with oral corticosteroids in the past month
- Need for maintenance oral corticosteroid therapy
- Pregnancy or planning to become pregnant over course of study and up to one month after
- Excessive risk of hepatotoxicity from endothelin receptor antagonists;
- Alcohol excess (defined as regular consumption above government daily recommend limits; currently defined as 28 units per wk for men, 21 units per week for women)
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- Previous intravenous drug use
- Current or known history of liver disease (with the exception of Gilberts disease and gallstones)
- Chronic hepatitis (either viral (e.g. hepatitis B or C) or autoimmune)
- Bilirubin, alanine aminotransferase (ALT) or asparate aminotransferase (AST) greater than the upper limit of normal at screening
- Anaemia (defined as haemoglobin below the lower reference range for sex) at screening
- Renal failure (defined as eGFR less than 50 mL/minute/1.73 m2) at screening
- Known HIV positivity
- History of inability to tolerate bosentan or ambrisentan
- Significant medical conditions other than asthma felt by investigator to preclude participation in study. This could be either in patients best interest or due to potential to significantly alter responses to medication and hence alter power of clinical trial (examples include; significant heart failure (NYHA grades II-IV), diabetes mellitus, bronchiectasis or haematological malignancy).
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Asthma Research Unit, University of Glasgow
Glasgow, G12 0YN
Mark Spears, MD PhD, 441412111673, mark.spears@glasgow.ac.uk
Rekha Chaudhuri, MD, 441412111673, rekhachaudhuri@yahoo.com
About this study
The purpose of this study will be to determine if blockade of endothelin 1 signalling via endothelin receptor A using ambrisentan or dual blockade (A\&B) via bosentan can provide protection against methacholine induced bronchoconstriction in asthma.
Read the detailed description
Endothelin 1 may have a role in the development of acute airway narrowing in asthma. Blockade of the endothelin system may thereby protect against airway narrowing. Two receptors exist for endothelin 1, Endothelin A \& B. Both can be blocked by Bosentan, and the A receptor by ambrisentan. Both medications are currently in use for the treatment of pulmonary arterial hypertension. The investigators will endeavour to examine the potential role of endothelin 1 in the development of airway narrowing in asthma through blockade of the endothelin receptors A\&B through the use of bosentan and ambrisentan.
- Conditions
- Asthma
- Being tested
- Ambrisentan, Bosentan, Placebo
- Keywords
- Asthma, Endothelin, Airway hyperreactivity
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
Also called Volibris
5mg od two weeks
BosentanDrug
Also called Tracleer
62.5mg bd two weeks
PlaceboDrug
bd for two weeks
| Study group | Role | What they receive |
|---|---|---|
| Ambrisentan | Experimental | 5mg od ambrisentan Receives: Drug: Ambrisentan |
| Bosentan | Experimental | 62.5mg bosentan Receives: Drug: Bosentan |
| 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.
Difference in doubling dose of methacholine to produce bronchoconstriction compared to placebo
Both active treatments will be compared against placebo with respect to protection against methacholine induced bronchoconstriction
Measured: 2 weeks
Secondary outcomes (1)
Which of the endothelin receptors A&B are most bronchoprotective against methacholine
Both bostentan and ambrisentans effect on airway response to methacholine will be compared to placebo. The relative efficacy will be compared, in terms of doubling doses of methacholine.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2012 (estimated)
- Study startNov 2012
- Primary completionMay 2014 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Glasgow
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Greater Glasgow and Clyde
- Responsible party
- Principal investigator, Mark Spears, University of Glasgow
- Investigators
- Mark Spears, MBChB PhD, Principal investigator, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01617746
- Sponsor's protocol ID
- AR012
- Status last verified
- Jun 2012
- First submitted
- 7 Mar 2012
- Last updated
- 12 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma
- ClinicalTrials.gov ID
- NCT01617746
- Acronym / sponsor ID
- AR012
- Conditions
- Asthma
- Keywords
- Asthma, Endothelin, Airway hyperreactivity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University of GlasgowUniversity, hospital or other
- Collaborators
- NHS Greater Glasgow and Clyde
- Study start
- Nov 2012
- Primary completion
- May 2014 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 12 Jun 2012 (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.
The purpose of this study will be to determine if blockade of endothelin 1 signalling via endothelin receptor A using ambrisentan or dual blockade (A\&B) via bosentan can provide protection against methacholine induced bronchoconstriction in asthma.
Detailed description
Endothelin 1 may have a role in the development of acute airway narrowing in asthma. Blockade of the endothelin system may thereby protect against airway narrowing. Two receptors exist for endothelin 1, Endothelin A \& B. Both can be blocked by Bosentan, and the A receptor by ambrisentan. Both medications are currently in use for the treatment of pulmonary arterial hypertension. The investigators will endeavour to examine the potential role of endothelin 1 in the development of airway narrowing in asthma through blockade of the endothelin receptors A\&B through the use of bosentan and ambrisentan.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ambrisentan | Experimental | Drug: Ambrisentan5mg od ambrisentan |
| Bosentan | Experimental | Drug: Bosentan62.5mg bosentan |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Physician diagnosis of asthma confirmed objectively by airway hyperactivity to methacholine (as determined by a ≥ 20% drop in FEV at a methacholine dose of ≤ 8mg/ml after β-agonist withdrawal as per ATS guidelines)
- Age range 18-60 years
- FEV1 ≥ 60% predicted
- Duration of asthma > 6 months and on stable medication for 4 weeks
- Prescribed and compliant with inhaled corticosteroid up to a maximum of 2000mcg beclomethasone or equivalent
Key exclusion criteria (15 listed)
- Unstable asthma; defined as the presence of 1 or more of the following events in the month prior to study [Emergency/'out of hours' visit to GP for asthma exacerbation; GP visit to patient at home for asthma exacerbation or A \& E/hospital admission for asthma exacerbation]
- Treatment with oral corticosteroids in the past month
- Need for maintenance oral corticosteroid therapy
- Pregnancy or planning to become pregnant over course of study and up to one month after
- Excessive risk of hepatotoxicity from endothelin receptor antagonists;
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 |
|---|---|---|
| AmbrisentanAlso: Volibris5mg od two weeks | Drug | Ambrisentan |
| BosentanAlso: Tracleer62.5mg bd two weeks | Drug | Bosentan |
| Placebobd for two weeks | Drug | Placebo |
Primary outcome
Difference in doubling dose of methacholine to produce bronchoconstriction compared to placebo
Time frame: 2 weeks
Both active treatments will be compared against placebo with respect to protection against methacholine induced bronchoconstriction
1 secondary outcome
Which of the endothelin receptors A&B are most bronchoprotective against methacholine
Time frame: 2 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2012.
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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.
Mark Spears, MBChB PhD principal investigator
University of Glasgow
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ambrisentan and Bosentan in people with Asthma, run by University of Glasgow 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 6 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 12 Jun 2012. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mark Spears, MBChB PhD (0141 211 1673, mark.spears@glasgow.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in doubling dose of methacholine to produce bronchoconstriction compared to placebo (time frame: 2 weeks). 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 12 Jun 2012; AzTrials last refreshed its copy on 8 Nov 2026.