Clinical trial NCT02682862: Ultra-long Acting Bronchodilator Therapy in Smoking Asthmatics
Official title: Effects of Ultra-long Acting Bronchodilator Therapy Assessed by Impulse Oscillometry in Smoking Asthmatics Taking Inhaled Corticosteroids
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: tiotropium
olodaterol
smoker
cigarette
bronchodilator
Lead sponsor: University of Dundee
Sponsor class: OTHER
First posted: 2016-02-17
Enrollment: 17
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: 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 Withdrawn subjects may be replaced.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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Airway resistance at 5Hz (R5)
timeFrame: 2-4 weeks
Secondary outcomes:
measure: RF
timeFrame: 2-4 weeks
measure: X5
timeFrame: 2-4 weeks
measure: AX
timeFrame: 2-4 weeks
measure: R5-R20
timeFrame: 2-4 weeks
measure: R20
timeFrame: 2-4 weeks
measure: FEF25-75 pre and post challenge
timeFrame: 2-4 weeks
measure: FVC pre and post challenge
timeFrame: 2-4 weeks
measure: FEV1 pre and post challenge
timeFrame: 2-4 weeks
measure: Mannitol PD30
timeFrame: 2-4 weeks
measure: Mannitol RDR
timeFrame: 2-4 weeks
measure: R5 at PD30
timeFrame: 2-4 weeks
measure: Salbutamol recovery time following mannitol challenge
timeFrame: 2-4 weeks
measure: Domiciliary PEF
timeFrame: 2-4 weeks
measure: ACQ
timeFrame: 2-4 weeks
Other outcomes:
Locations:
city: Dundee
country: United Kingdom
facility: Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School
state: Scotland
Study officials:
affiliation: University of Dundee
name: Sunny Jabbal, Mb Chb
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Dundee
name: Brian Lipworth, MD, Mb Chb
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lipworth B, RuiWen Kuo C, Jabbal S, Chan R. Inhaled triple therapy and airway hyperresponsiveness in persistent asthma. Ann Allergy Asthma Immunol. 2021 May;126(5):597-598. doi: 10.1016/j.anai.2021.01.032. Epub 2021 Feb 3. No abstract available.
citation: Jabbal S, Kuo CR, Lipworth B. Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics. Clin Exp Allergy. 2020 Oct;50(10):1140-1147. doi: 10.1111/cea.13702. Epub 2020 Jul 27.