Clinical trial NCT01544634: Beta Blocker Therapy in Mild to Moderate Asthmatics
Official title: Evaluation of Any Steroid Sparing Effect of Beta Blocker Therapy on Airway Hyper-responsiveness in Stable, Mild to Moderate Asthmatics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Propranolol
Inhaled corticosteroids
Steroid sparing agent
Airway hyper-responsiveness
Lead sponsor: University of Dundee
Sponsor class: OTHER
Collaborators: name: Chief Scientist Office of the Scottish Government
First posted: 2012-03-06
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Histamine provocative concentration causing 20% fall in FEV1 (PC20)at 6 weeks
timeFrame: Change from baseline to 6 weeks
Secondary outcomes:
measure: Change in Impulse oscillometry parameters at 6 weeks
timeFrame: Change from baseline to 6 weeks
measure: Change in Spirometry parameters at 6 weeks
timeFrame: Change from baseline to 6 weeks
measure: Change in resting heart rate at 6 weeks
timeFrame: Change from baseline to 6 weeks
measure: Change in resting blood pressure at 6 weeks
timeFrame: Change from baseline to 6 weeks
measure: Change in exhaled tidal nitric oxide levels at 6 weeks
timeFrame: Change from baseline to 6 weeks
measure: Change in overnight urinary cortisol/creatinine ratio (OUCC) at 6 weeks
timeFrame: Change from baseline to 6 weeks
measure: Change in symptom scores (Asthma control questionnaire and Asthma quality of life questionnaire) at 6 weeks
timeFrame: Change from baseline to 6 weeks
Other outcomes:
Locations:
city: Dundee
country: United Kingdom
facility: Asthma and Allergy Research Group, University of Dundee
state: Scotland
Study officials:
affiliation: University of Dundee
name: William J Anderson, MBChB
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Dundee
name: Brian J Lipworth, MD
role: STUDY_DIRECTOR
References:
citation: Morales DR, Guthrie B, Lipworth BJ, Donnan PT, Jackson C. Prescribing of beta-adrenoceptor antagonists in asthma: an observational study. Thorax. 2011 Jun;66(6):502-7. doi: 10.1136/thoraxjnl-2011-200067. Epub 2011 Apr 1.
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. doi: 10.1016/j.pupt.2007.06.003. Epub 2007 Jul 4.
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. doi: 10.1165/rcmb.2007-0279RC. Epub 2007 Dec 20.
citation: 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. doi: 10.1016/j.pupt.2007.07.002. Epub 2007 Jul 17.
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.
citation: Anderson WJ, Short PM, Jabbal S, Lipworth BJ. Inhaled corticosteroid dose response in asthma: Should we measure inflammation? Ann Allergy Asthma Immunol. 2017 Feb;118(2):179-185. doi: 10.1016/j.anai.2016.11.018. Epub 2017 Jan 3.
citation: Anderson WJ, Short PM, Williamson PA, Manoharan A, Lipworth BJ. The inverse agonist propranolol confers no corticosteroid-sparing activity in mild-to-moderate persistent asthma. Clin Sci (Lond). 2014 Dec;127(11):635-43. doi: 10.1042/CS20140249.