Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2012 by University of Glasgow
Sponsor:
Collaborator:
NHS Greater Glasgow and Clyde
Information provided by (Responsible Party):
Mark Spears, University of Glasgow
ClinicalTrials.gov Identifier:
NCT01617746
First received: March 7, 2012
Last updated: June 10, 2012
Last verified: June 2012

March 7, 2012
June 10, 2012
November 2012
May 2014   (final data collection date for primary outcome measure)
Difference in doubling dose of methacholine to produce bronchoconstriction compared to placebo [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
Both active treatments will be compared against placebo with respect to protection against methacholine induced bronchoconstriction
Same as current
Complete list of historical versions of study NCT01617746 on ClinicalTrials.gov Archive Site
Which of the endothelin receptors A&B are most bronchoprotective against methacholine [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
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.
Same as current
Not Provided
Not Provided
 
Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma
Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Asthma
  • Drug: Ambrisentan
    5mg od two weeks
    Other Name: Volibris
  • Drug: Bosentan
    62.5mg bd two weeks
    Other Name: Tracleer
  • Drug: Placebo
    bd for two weeks
  • Experimental: Ambrisentan
    5mg od ambrisentan
    Intervention: Drug: Ambrisentan
  • Experimental: Bosentan
    62.5mg bosentan
    Intervention: Drug: Bosentan
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
18
December 2015
May 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. 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)
  2. Age range 18-60 years
  3. FEV1 ≥ 60% predicted
  4. Duration of asthma > 6 months and on stable medication for 4 weeks
  5. Prescribed and compliant with inhaled corticosteroid up to a maximum of 2000mcg beclomethasone or equivalent
  6. No history of previous regular smoking and current non-smoker

Exclusion Criteria:

  1. 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]
  2. Treatment with oral corticosteroids in the past month
  3. Need for maintenance oral corticosteroid therapy
  4. Pregnancy or planning to become pregnant over course of study and up to one month after
  5. 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
  6. Anaemia (defined as haemoglobin below the lower reference range for sex) at screening
  7. Renal failure (defined as eGFR less than 50 mL/minute/1.73 m2) at screening
  8. Known HIV positivity
  9. History of inability to tolerate bosentan or ambrisentan
  10. 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).
Both
18 Years to 60 Years
No
Contact: Mark Spears, MBChB PhD 0141 211 1673 mark.spears@glasgow.ac.uk
Contact: Rekha Chaudhuri, MD 0141 211 1673 rekhachaudhuri@yahoo.com
United Kingdom
 
NCT01617746
AR012
No
Mark Spears, University of Glasgow
University of Glasgow
NHS Greater Glasgow and Clyde
Principal Investigator: Mark Spears, MBChB PhD University of Glasgow
University of Glasgow
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP