Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01617746
Verified June 2012 by Mark Spears, University of Glasgow. Recruitment status was: Not yet recruiting
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.
Condition or disease
Drug: AmbrisentanDrug: BosentanDrug: Placebo
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study:
18 Years to 60 Years (Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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
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)
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).