Beta Blocker Therapy in Mild to Moderate Asthmatics

Asthma Clinical Trial

— ANDA1  

Official title:

Evaluation of Any Steroid Sparing Effect of Beta Blocker Therapy on Airway Hyper-responsiveness in Stable, Mild to Moderate Asthmatics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01544634
• Other study ID #: 2011RC16
• Secondary ID: 2011-002512-89
• Status: Completed
• Phase: Phase 2
• First received: February 24, 2012
• Last updated: March 29, 2018
• Start date: April 4, 2012
• Est. completion date: May 25, 2013

Study information

• Verified date: March 2018
• Source: University of Dundee
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Current asthma medicines include inhalers. A common type of inhaler is called a 'beta-agonist' (e.g. salbutamol). They improve asthma symptoms by stimulating areas in the airway causing it to widen. Although these drugs are useful short term, long term use can make asthma worse in some people.

'Beta-blockers' are the complete opposite type of medication. Just now they are avoided in patients with asthma. Beta-blockers cause problems in asthmatics in the short term, including severe asthma attacks.

The other mainstay of inhaler treatment for asthma is inhaled steroid or 'preventer' medication. These work by dampening down the inflammation in the lungs that occurs in asthma.

New research has suggested that longer term use of beta-blockers can also reduce airway inflammation which may improve asthma control. This research was done in asthmatic patients who didn't need inhaled steroids to control their asthma. At the moment the investigators are studying to see if there is a benefit of beta-blocker use for asthma over and above asthmatics own usual doses of inhaled steroids.

In this study, the investigators will be trying to find out if adding a beta blocker to a smaller dose of steroid inhaler has the same effect on asthma control as just using a higher dose of steroid inhaler by itself.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: May 25, 2013
• Est. primary completion date: May 25, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Stable mild to moderate asthma

• Histamine PC20 </= 8mg/ml

• Receiving inhaled corticosteroid 0-1000ug daily (BDP equivalent dose)

• FEV1 > 60% predicted

• Diurnal variability < 30%

• Reliever use </= 8puffs/day

• ECG demonstrating sinus rhythm

Exclusion Criteria:

• Uncontrolled symptoms of asthma

• Systolic BP<110mmHg

• Heart rate<60bpm

• Pregnancy or lactation

• Heart block

• Heart rate limiting medications currently prescribed

• Asthma exacerbation within 6 months of study commencement

Related Conditions & MeSH terms

• Asthma
• Respiratory Hypersensitivity

Intervention

Drug:
• Propranolol
Propranolol: 10mg bd for 1 week, 20mg bd for 2 weeks, 80mg MR for 4 weeks.
• Placebo
Placebo tablets: 1 tab bd for 2 weeks, 1 tab od for 4 weeks
• Qvar 50
Qvar 50, 1 puff bd for 6 weeks
• Qvar 100
Qvar 100, 2 puffs bd for 6 weeks

Locations

Country	Name	City	State
United Kingdom	Asthma and Allergy Research Group, University of Dundee	Dundee	Scotland

Sponsors (2)

Lead Sponsor	Collaborator
University of Dundee	Chief Scientist Office of the Scottish Government

Country where clinical trial is conducted

United Kingdom, 

References & Publications (5)

Hanania NA, Singh S, El-Wali R, Flashner M, Franklin AE, Garner WJ, Dickey BF, Parra S, Ruoss S, Shardonofsky F, O'Connor BJ, Page C, Bond RA. The safety and effects of the beta-blocker, nadolol, in mild asthma: an open-label pilot study. Pulm Pharmacol Ther. 2008;21(1):134-41. Epub 2007 Jul 17. — View Citation

Lin R, Peng H, Nguyen LP, Dudekula NB, Shardonofsky F, Knoll BJ, Parra S, Bond RA. Changes in beta 2-adrenoceptor and other signaling proteins produced by chronic administration of 'beta-blockers' in a murine asthma model. Pulm Pharmacol Ther. 2008;21(1):115-24. Epub 2007 Jul 4. — View Citation

Lipworth BJ, Williamson PA. Think the impossible: beta-blockers for treating asthma. Clin Sci (Lond). 2009 Oct 12;118(2):115-20. doi: 10.1042/CS20090398. — View Citation

Morales DR, Guthrie B, Lipworth BJ, Donnan PT, Jackson C. Prescribing of ß-adrenoceptor antagonists in asthma: an observational study. Thorax. 2011 Jun;66(6):502-7. doi: 10.1136/thoraxjnl-2011-200067. Epub 2011 Apr 1. — View Citation

Nguyen LP, Omoluabi O, Parra S, Frieske JM, Clement C, Ammar-Aouchiche Z, Ho SB, Ehre C, Kesimer M, Knoll BJ, Tuvim MJ, Dickey BF, Bond RA. Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model. Am J Respir Cell Mol Biol. 2008 Mar;38(3):256-62. Epub 2007 Dec 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Histamine provocative concentration causing 20% fall in FEV1 (PC20)at 6 weeks	Measurement of airway hyper-reactivity (a hallmark of asthma).	Change from baseline to 6 weeks
Secondary	Change in Impulse oscillometry parameters at 6 weeks	Change in: Resistance at 5Hz, Resistance at 20Hz, Reactance at 5Hz, Frequency of resonance, Area under reactance curve.	Change from baseline to 6 weeks
Secondary	Change in Spirometry parameters at 6 weeks	Change in: Forced expiratory volume in 1 second (FEV1); forced vital capacity (FVC); forced expriatory flow between 25-75% of vital capacity; FEV1/FVC ratio.	Change from baseline to 6 weeks
Secondary	Change in resting heart rate at 6 weeks	Abosolute change in heart rate at 6 weeks will be a secondary outcome. Participants will measure their own heart rate at home on a daily basis and compare this to a given cut-off value, below which they will be advised to contact a trial doctor.	Change from baseline to 6 weeks
Secondary	Change in resting blood pressure at 6 weeks	Blood pressure will be monitored at each visit, or if patients develop symptoms that may be due to low blood pressure.	Change from baseline to 6 weeks
Secondary	Change in exhaled tidal nitric oxide levels at 6 weeks		Change from baseline to 6 weeks
Secondary	Change in overnight urinary cortisol/creatinine ratio (OUCC) at 6 weeks	Systemic effects from inhaled corticosteroids can be measured using OUCC.	Change from baseline to 6 weeks
Secondary	Change in symptom scores (Asthma control questionnaire and Asthma quality of life questionnaire) at 6 weeks		Change from baseline to 6 weeks