Reversal of Acute β-Blocker Induced Bronchoconstriction

NCT01070225 | Completed Phase 4 DMC

• 1 other identifier: SHO001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Current therapies for the management of asthma include inhalers. Types of these medications (beta agonists), improve asthma symptoms by stimulating areas (receptors) within the human airway resulting in dilation of the human airway. Whilst these drugs are highly effectively in the immediate setting their longterm use, constantly stimulation of receptors within the airway has been associated with increased asthma exacerbations and rare cases of death. Conversely medications that block receptors within the human airway (betablockers)have been avoided in asthma. The main reason for this is because of the possible acute airway narrowing that can occur after soon after administration. However chronic use of betablockers in asthma has recently been shown to be of benefit in reducing airway inflammation which is of great importance in improving asthma control and reducing symptoms. Despite this early evidence supporting chronic use of beta blockers in asthma, there is concern in 2 major regards:their potential to cause acute airway narrowing (irrespective of longterm benefit) and the possibility that they could block the reliever action of beta agonists. The objective of this study is to establish how best to reverse the short term effects of a single dose of beta blocker. This study is designed as a single centre study, with participants attending the department on approximately 3 separate visits (including a screening visit) at approximately 1 weekly intervals.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• To establish whether acute β-blockade influences the ability to achieve airway reversibility and recovery with systemic corticosteroids and nebulised bronchodilators following histamine challenge in mild to moderate asthmatics.

  3 weeks

Study Arms (2)

Hydrocortisone and Propranolol

EXPERIMENTAL

Participant administered 10 or 20mg propranolol orally. Participants meeting the parameters are randomised to receive 400mg Hydrocortisone intravenously. Participant then receives Histamine PC10 challenge, Administered 5mg Salbutamol via nebuliser, administered 500mcg Ipratropium Bromide via nebuliser; visit end

Drug: Hydrocortisone/ Placebo and Propranolol

Placebo and propranolol

PLACEBO COMPARATOR

identical to other arm but participant receive placebo injection as opposed to hydrocortisone

Drug: Hydrocortisone/ Placebo and Propranolol

Interventions

Hydrocortisone/ Placebo and Propranolol DRUG

Hydrocortisone 400mcg Propranolol 10mg or 20 mg

Hydrocortisone and Propranolol; Placebo and propranolol

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to obtain Informed consent.
• Mild to Moderate Asthmatics taking ≤1000μg BDP per day or equivalent.
• Histamine PC10
• Ability to perform spirometry, IOS, bronchial challenge and all domiciliary measurements.
• Withhold LABAs, montelukast and theophyllines for 1 week prior to study.
• FEV1 \>80% predicted with diurnal FEV1 variation \<20% post wash out.

You may not qualify if:

• Uncontrolled symptoms of asthma.
• Resting BP\<110 systolic or HR\<60.
• Pregnancy or lactation.
• Known or suspected sensitivity to IMP.
• Inability to comply with protocol.
• Any degree of heart block.
• Rate limiting medication including β blockers, rate limiting Calcium Channel Blockers and Amiodarone.
• Any other clinically significant medical condition that may either endanger the health or safety of the participant, or jeopardise the protocol.

Sponsors & Collaborators

• University of Dundee: lead
• NHS Tayside: collaborator

Study Sites (1)

Asthma and Allergy Research Group, Unviersity of Dundee

Dundee, DD2 1QQ, United Kingdom

Location

Related Publications (1)

• Short PM, Williamson PA, Lipworth BJ. Effects of hydrocortisone on acute beta-adrenoceptor blocker and histamine induced bronchoconstriction. Br J Clin Pharmacol. 2012 May;73(5):717-26. doi: 10.1111/j.1365-2125.2011.04143.x.

  PMID: 22077869 RESULT

MeSH Terms

Conditions

Asthma

Interventions

Hydrocortisone; Propranolol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Brian J Lipworth, MD

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor (Clinical) Airway allergy and COPD

Study Record Dates

• First Submitted: February 16, 2010
• First Posted: February 17, 2010
• Study Start: March 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: October 1, 2010
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

GB (1)