Beta Blocker Therapy in Mild to Moderate Asthmatics

Study Overview
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Brief Summary
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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.

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

Conditions
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Asthma

Intervention / Treatment
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* Drug: Propranolol
* Drug: Placebo
* Drug: Qvar 50
* Drug: Qvar 100


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propranolol + Low dose Qvar<br> | Drug: Propranolol<br>* Propranolol: 10mg bd for 1 week, 20mg bd for 2 weeks, 80mg MR for 4 weeks.<br>Drug: Qvar 50<br>* Qvar 50, 1 puff bd for 6 weeks<br>|
| Active Comparator: Placebo + high dose Qvar<br> | Drug: Placebo<br>* Placebo tablets: 1 tab bd for 2 weeks, 1 tab od for 4 weeks<br>Drug: Qvar 100<br>* Qvar 100, 2 puffs bd for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Change in exhaled tidal nitric oxide levels at 6 weeks |  | Change from baseline to 6 weeks | 
| 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 | 
| Change in symptom scores (Asthma control questionnaire and Asthma quality of life questionnaire) at 6 weeks |  | Change from baseline to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Propranolol, Inhaled corticosteroids, Steroid sparing agent, Airway hyper-responsiveness