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
  Purpose

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 Intervention Phase
Asthma
Drug: Ambrisentan
Drug: Bosentan
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma

Resource links provided by NLM:


Further study details as provided by University of Glasgow:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 18
Study Start Date: November 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ambrisentan
5mg od ambrisentan
Drug: Ambrisentan
5mg od two weeks
Other Name: Volibris
Experimental: Bosentan
62.5mg bosentan
Drug: Bosentan
62.5mg bd two weeks
Other Name: Tracleer
Placebo Comparator: Placebo Drug: Placebo
bd for two weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01617746

Contacts
Contact: Mark Spears, MBChB PhD 0141 211 1673 mark.spears@glasgow.ac.uk
Contact: Rekha Chaudhuri, MD 0141 211 1673 rekhachaudhuri@yahoo.com

Locations
United Kingdom
Asthma Research Unit, University of Glasgow Not yet recruiting
Glasgow, United Kingdom, G12 0YN
Contact: Mark Spears, MD PhD    441412111673    mark.spears@glasgow.ac.uk   
Contact: Rekha Chaudhuri, MD    441412111673    rekhachaudhuri@yahoo.com   
Principal Investigator: Mark Spears, MD PhD         
Sub-Investigator: Rekha Chaudhuri         
Sub-Investigator: Neil C Thomson, MD FRCP         
Sponsors and Collaborators
University of Glasgow
NHS Greater Glasgow and Clyde
Investigators
Principal Investigator: Mark Spears, MBChB PhD University of Glasgow
  More Information

No publications provided

Responsible Party: Mark Spears, Clinical Lecturer, University of Glasgow
ClinicalTrials.gov Identifier: NCT01617746     History of Changes
Other Study ID Numbers: AR012
Study First Received: March 7, 2012
Last Updated: June 10, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Glasgow:
Asthma
Endothelin
Airway hyperreactivity

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Bosentan
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014