AsthmaPhase 4NCT01070225
Reversal of Acute β-Blocker Induced Bronchoconstriction
A Phase 4 study of Asthma, run by University of Dundee at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2010to Oct 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Asthma and Allergy Research Group, Unviersity of Dundee
Dundee, DD2 1QQ
About this study
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.
Read more
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.
Read the detailed description
Asthma was originally thought to be associated with an intrinsic defect of β2- adrenoceptor function tipping the balance towards parasympathetic bronchoconstriction. While β2-agonists are highly effective for the acute relief of bronchoconstriction, their chronic use is accompanied by an adaptive reduction in β2ADR numbers and associated desensitisation of response, resulting in increased exacerbations and rare cases of death. Conversely the chronic use of β blockers have been shown in murine models to reduce airway inflammation and mucous metaplasia. Recent work in humans has further demonstrated a potential benefit of β blockers in asthmatics by demonstrating a significant improvement in airway hyperresponsiveness to bronchial challenge1.
Despite this early evidence supporting chronic use of β blockers in asthma, there is concern in 2 major regards: their potential to cause acute bronchoconstriction (irrespective of long-term benefit) and the possibility that they could block the reliever action of β-agonists.
Sub-sensitivity of β-adrenoceptors occurs following treatment with long-acting β-agonists. Previous work in our department has shown that high dose steroids can re-establish the β-adrenoceptor function following such down-regulation2. It therefore seems plausible that a similar response may occur following β-blockade (reversing β-blockade and re-establishing β-agonist sensitivity).
The investigators wish to gather evidence for the best methods to treat β-blocked patients in the short term. The investigators therefore wish to examine the effects of acute-β blockade with low dose propranolol on mild-to-moderate asthmatics. The investigators wish to simulate airway stress and rescue in acutely β-blocked patients. For safety purposes the investigators have chosen propranolol due to its short half-life of 3 to 5 hours. Importantly the ability to achieve airway reversibility and recovery following acute β-blockade will influence the long term viability of chronic β blockers use in the management of asthma.
- Conditions
- Asthma
- Being tested
- Hydrocortisone/ Placebo and Propranolol
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydrocortisone/ Placebo and PropranololDrug
Hydrocortisone 400mcg Propranolol 10mg or 20 mg
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Hydrocortisone/ Placebo and Propranolol |
| Placebo and propranolol | Placebo comparator | identical to other arm but participant receive placebo injection as opposed to hydrocortisone Receives: Drug: Hydrocortisone/ Placebo and Propranolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2010 (estimated)
- Study startMar 2010
- Primary completionAug 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Tayside
- Responsible party
- Principal investigator, Brian J Lipworth, University of Dundee
- Investigators
- Brian J Lipworth, MD, Principal investigator, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01070225
- Sponsor's protocol ID
- SHO001
- Status last verified
- Apr 2019
- First submitted
- 16 Feb 2010
- Last updated
- 12 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22077869
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reversal of Acute β-Blocker Induced Bronchoconstriction
- ClinicalTrials.gov ID
- NCT01070225
- Acronym / sponsor ID
- SHO001
- Conditions
- Asthma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- NHS Tayside
- Study start
- Mar 2010
- Primary completion
- Aug 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 17 Feb 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Asthma was originally thought to be associated with an intrinsic defect of β2- adrenoceptor function tipping the balance towards parasympathetic bronchoconstriction. While β2-agonists are highly effective for the acute relief of bronchoconstriction, their chronic use is accompanied by an adaptive reduction in β2ADR numbers and associated desensitisation of response, resulting in increased exacerbations and rare cases of death. Conversely the chronic use of β blockers have been shown in murine models to reduce airway inflammation and mucous metaplasia. Recent work in humans has further demonstrated a potential benefit of β blockers in asthmatics by demonstrating a significant improvement in airway hyperresponsiveness to bronchial challenge1.
Despite this early evidence supporting chronic use of β blockers in asthma, there is concern in 2 major regards: their potential to cause acute bronchoconstriction (irrespective of long-term benefit) and the possibility that they could block the reliever action of β-agonists.
Sub-sensitivity of β-adrenoceptors occurs following treatment with long-acting β-agonists. Previous work in our department has shown that high dose steroids can re-establish the β-adrenoceptor function following such down-regulation2. It therefore seems plausible that a similar response may occur following β-blockade (reversing β-blockade and re-establishing β-agonist sensitivity).
The investigators wish to gather evidence for the best methods to treat β-blocked patients in the short term. The investigators therefore wish to examine the effects of acute-β blockade with low dose propranolol on mild-to-moderate asthmatics. The investigators wish to simulate airway stress and rescue in acutely β-blocked patients. For safety purposes the investigators have chosen propranolol due to its short half-life of 3 to 5 hours. Importantly the ability to achieve airway reversibility and recovery following acute β-blockade will influence the long term viability of chronic β blockers use in the management of asthma.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydrocortisone and Propranolol | Experimental | Drug: Hydrocortisone/ Placebo and PropranololParticipant 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 |
| Placebo and propranolol | Placebo comparator | Drug: Hydrocortisone/ Placebo and Propranololidentical to other arm but participant receive placebo injection as opposed to hydrocortisone |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydrocortisone/ Placebo and PropranololHydrocortisone 400mcg Propranolol 10mg or 20 mg | Drug | Hydrocortisone and Propranolol, Placebo and propranolol |
Primary outcome
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.
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2019.
- Results publication: PubMed 22077869Short 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian J Lipworth, MD principal investigator
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study of Asthma, run by University of Dundee at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01070225, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2019.