Ultra-long Acting Bronchodilator Therapy in Smoking Asthmatics (MAN05)

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

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 Withdrawn subjects may be replaced.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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg; Drug: olodaterol 2.5 mcg

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Spiolto Respimat; 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; Inhaler: 2.5 microgram tiotropium (as bromide monohydrate) and 2.5 microgram olodaterol (as hydrochloride) per puff. 2 puffs once daily; Other Names: Spiolto Respimat 2.5mcg/2.5mcg
Active Comparator: Striverdi Respimat; 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; Inhaler: 2.5 microgram Olodaterol (as hydrochloride) per puff. 2 puffs once daily; Other Names: Striverdi Respimat 2.5mcg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Dundee
• Investigators: Principal Investigator: Sunny Jabbal, Mb Chb, University of Dundee; Principal Investigator: Brian Lipworth, MD, Mb Chb, University of Dundee

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2016
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): May 22, 2019

Study Registration Dates

• First Submitted: February 4, 2016
• First Submitted That Met QC Criteria: February 10, 2016
• First Posted (Estimate): February 17, 2016

Study Record Updates

• Last Update Posted (Actual): June 21, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: cigarette; tiotropium; bronchodilator; smoker; olodaterol
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides; Olodaterol
• Other Study ID Numbers: 2013RC06; 2014-005317-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO