Ultra-long Acting Bronchodilator Therapy in Asthmatics

Study Overview
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Brief Summary
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Asthma is a common condition which produces a significant workload for general practice, hospital outpatient clinics and inpatient admissions. Asthma is caused by inflammation of the airways which irritates the muscles around the airways causing them to constrict. The mainstay of asthma treatment is inhaled steroids. If the patients' symptoms are still not adequately controlled, then a long-acting beta agonist (LABA) inhaler which relaxes the muscles in the airways and opens it up is frequently added to the inhaled steroids. Despite this, a substantial proportion of asthmatic patients still do not achieve adequate control of their symptoms. Recent studies have shown when an alternative inhaler called a long-acting muscarinic antagonist (LAMA) is added to a LABA - it reduced the number of asthma exacerbations (flare-ups) and improved airway narrowing. The mannitol challenge is a test of airway 'twitchiness', an important feature of asthma. There have been no previous studies assessing the combined effects LABA and LAMA inhalers on mannitol challenge. The mannitol challenge is particularly relevant as it mimics stimuli encountered in real life which provoke an asthma attack. The investigators propose to directly compare indacaterol, a new once-daily LABA with indacaterol plus tiotropium, a once-daily LAMA, as add-on treatment to inhaled steroids in persistent asthmatics using the mannitol challenge. The investigators hope that this study will help us understand how the combination of a LABA and LAMA might help protect against flare-ups.

Official Title
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Proof of Concept Study to Evaluate Single and Chronic Dosing Effects of Ultra-long Acting Bronchodilator Therapy on Mannitol Challenge in Asthmatic Patients Taking Inhaled Corticosteroids

Conditions
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Asthma

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Indacaterol and tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female volunteers aged at least 16 years with persistent asthma and on inhaled corticosteroids (at least 400 micrograms of beclomethasone dipropionate or the equivalent FEV1 > 50 % predicted Mannitol PD15 < 635 mg 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 respiratory diseases such as chronic obstructive pulmonary disease, bronchiectasis or allergic bronchopulmonary aspergillosis An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 3 months of the study commencement Any clinically significant medical condition that may endanger the health or safety of the participant Smoking within one year or >10 pack year history Participation in another trial within 30 days before the commencement of the study Pregnancy or lactation Unable to comply with the procedures of the protocol

Ages Eligible for Study
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Minimum Age: 16 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 |
| --- | --- |
| Active Comparator: Indacaterol<br> | Drug: Indacaterol<br>* Participants receive indacaterol for 2 to 4 weeks. Participants then enter a washout period and after the washout period receive the alternative treatment arm.<br>|
| Experimental: Indacaterol & tiotropium<br> | Drug: Indacaterol and tiotropium<br>* Participants receive indacaterol and tiotropium for 2 to 4 weeks. Participants then enter a washout period and after the washout period receive the alternative treatment arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in provocation dose of mannitol causing 15% drop in forced expiratory volume in 1 second (PD15) between single and chronic dosing of ultra-long acting bronchodilator therapy |  | 2 to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mannitol Response-dose Ratio (RDR) |  | 2 to 4 weeks | 
| Salbutamol recovery time following mannitol challenge |  | 2 to 4 weeks | 
| Domiciliary peak expiratory flow (PEF) |  | 2 to 4 weeks | 
| Trough forced expiratory volume in 1 second (FEV1) |  | 2 to 4 weeks | 
| Exhaled nitric oxide (FeNO) |  | 2 to 4 weeks | 
| Trough impulse oscillometry (IOS) |  | 2 to 4 weeks | 
| Asthma Control Questionnaire (ACQ) |  | 2 to 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Long acting beta-agonists, Long acting muscarinic antagonists, Mannitol challenge