Examination of the Bronchoprotective Effect of Endothelin Receptor Blockade in Asthma

NCT01617746 | Unknown Phase 2

• 1 other identifier: AR012
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Asthma

Keywords

Asthma; Endothelin; Airway hyperreactivity

Outcome Measures

Primary Outcomes (1)

• 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

  2 weeks

Secondary Outcomes (1)

• Which of the endothelin receptors A&B are most bronchoprotective against methacholine

  2 weeks

Study Arms (3)

Ambrisentan

EXPERIMENTAL

5mg od ambrisentan

Drug: Ambrisentan

Bosentan

EXPERIMENTAL

62.5mg bosentan

Drug: Bosentan

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ambrisentan DRUG

5mg od two weeks

Also known as: Volibris

Ambrisentan

Bosentan DRUG

62.5mg bd two weeks

Also known as: Tracleer

Bosentan

Placebo DRUG

bd for two weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Glasgow: lead
• NHS Greater Glasgow and Clyde: collaborator

Study Sites (1)

Asthma Research Unit, University of Glasgow

Glasgow, G12 0YN, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

ambrisentan; Bosentan

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mark Spears, MBChB PhD

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Spears, MBChB PhD

CONTACT

0141 211 1673; mark.spears@glasgow.ac.uk

Rekha Chaudhuri, MD

CONTACT

0141 211 1673; rekhachaudhuri@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Lecturer

Study Record Dates

• First Submitted: March 7, 2012
• First Posted: June 12, 2012
• Study Start: November 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: December 1, 2015
• Last Updated: June 12, 2012

Record last verified: 2012-06

Locations

GB (1)