Ultra-long Acting Bronchodilator Therapy in Smoking Asthmatics

Study Overview
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Brief Summary
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Single centre, open-label, random order, cross-over trial, recruited over a period of approximately 2 years. Sufficient participants enrolled to complete 16 adults. Withdrawn subjects may be replaced. This clinical trial will assess the effects of ultra-long acting bronchodilator therapy in smoking asthmatics taking inhaled corticosteroids. This will be via a pulmonary function test called impulse oscillometry.

Detailed Description
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Cigarette smoking in asthma is associated with poorer asthma control and a higher frequency of asthma attacks. Despite this, smoking cessation rates are very low due to the highly addictive nature of tobacco smoking. Asthma in smokers is particularly challenging to manage because it is resistant to the beneficial effects of inhaled corticosteroids, the main treatment for asthma. Unfortunately, there is no guideline consensus regarding how to best manage asthmatics who smoke. Research studies in asthma tend to exclude smokers because of concerns about recruiting patients with chronic obstructive pulmonary disease (COPD). Hence, there is an unmet need for research studies in asthmatics who are unable to stop smoking. In view of the above, we propose to assess the effects of two different types of bronchodilators (inhalers which help open up the airways), in asthmatics who continue to smoke. Participants will receive both of the following drugs for 2-4 weeks in random order, with a 2-3 week washout period in between: Olodaterol which is a new long-acting bronchodilator. Olodaterol combined with tiotropium (dual bronchodilators). We wish to compare these inhalers using a sensitive pulmonary function test called impulse oscillometry.

Official Title
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Effects of Ultra-long Acting Bronchodilator Therapy Assessed by Impulse Oscillometry in Smoking Asthmatics Taking Inhaled Corticosteroids

Conditions
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Asthma

Intervention / Treatment
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* Drug: olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg
* Drug: olodaterol 2.5 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female volunteers aged 18-65 years with persistent asthma and on inhaled corticosteroids (at least 400 micrograms beclomethasone dipropionate equivalent dose daily) Current smoker Forced Expiratory Volume in 1 second (FEV1) ≥ 60 % predicted Ability to give informed consent Agreement for their General Practitioner to be made aware of study participation and to receive feedback as relevant to the participant's well being Exclusion Criteria: Other significant respiratory diseases, in the opinion of the investigator, such as COPD or bronchiectasis. An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement or 3 months if hospital admission was required Any clinically significant medical condition that may endanger the health or safety of the participant Participation in another drug trial within 30 days before the commencement of the study Pregnancy or lactation Unable to comply with the procedures of the protocol Unable or unwilling to consent

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spiolto Respimat<br>olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm | Drug: olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg<br>* Inhaler: 2.5 microgram tiotropium (as bromide monohydrate) and 2.5 microgram olodaterol (as hydrochloride) per puff. 2 puffs once daily<br>* Other names: Spiolto Respimat 2.5mcg/2.5mcg;|
| Active Comparator: Striverdi Respimat<br>olodaterol 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm | Drug: olodaterol 2.5 mcg<br>* Inhaler: 2.5 microgram Olodaterol (as hydrochloride) per puff. 2 puffs once daily<br>* Other names: Striverdi Respimat 2.5mcg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway resistance at 5Hz (R5) | measured by Impulse oscillometry (IOS) | 2-4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RF | Impulse Oscillometry: Resonant Frequency | 2-4 weeks | 
| X5 | Impulse Oscillometry: Reactance at 5Hz | 2-4 weeks | 
| AX | Impulse Oscillometry: Reactance Area | 2-4 weeks | 
| R5-R20 | Impulse Oscillometry: Resistance at 5Hz minus Resistance at 20Hz, equating to small airway resistance | 2-4 weeks | 
| R20 | Impulse Oscillometry: Resistance at 20Hz | 2-4 weeks | 
| FEF25-75 pre and post challenge | Spirometry: Forced expiratory flow 25%-75% pre and post bronchial challenge (assessing change) | 2-4 weeks | 
| FVC pre and post challenge | Spirometry: Forced vital capacity pre and post bronchial challenge (assessing change) | 2-4 weeks | 
| FEV1 pre and post challenge | Spirometry: Forced expiratory volume in 1 second pre and post bronchial challenge (assessing change) | 2-4 weeks | 
| Mannitol PD30 | Provocation dose of mannitol causing 30% increase in R5 | 2-4 weeks | 
| Mannitol RDR | Response-Dose Ratio | 2-4 weeks | 
| R5 at PD30 | Airway Resistance at 5 Hertz at PD30 | 2-4 weeks | 
| Salbutamol recovery time following mannitol challenge |  | 2-4 weeks | 
| Domiciliary PEF | Peak Expiratory Flow | 2-4 weeks | 
| ACQ | Asthma Control Questionnaire | 2-4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tiotropium, olodaterol, smoker, cigarette, bronchodilator