Ultra-long Acting Bronchodilator Therapy in Asthmatics

NCT02039011 | Completed Phase 4

• 1 other identifier: 2012RC15
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma

Keywords

Asthma; Long acting beta-agonists; Long acting muscarinic antagonists; Mannitol challenge

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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

Study Arms (2)

Indacaterol

ACTIVE COMPARATOR

Drug: Indacaterol

Indacaterol & tiotropium

EXPERIMENTAL

Drug: Indacaterol and tiotropium

Interventions

Indacaterol DRUG

Participants receive indacaterol for 2 to 4 weeks. Participants then enter a washout period and after the washout period receive the alternative treatment arm.

Indacaterol

Indacaterol and tiotropium DRUG

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.

Indacaterol & tiotropium

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Dundee: lead
• Tenovus Scotland: collaborator

Study Sites (1)

Asthma and Allergy Research Group, University of Dundee

Dundee, DD1 3AU, United Kingdom

Location

Related Publications (1)

• Jabbal S, Manoharan A, Lipworth BJ. Bronchoprotective tolerance with indacaterol is not modified by concomitant tiotropium in persistent asthma. Clin Exp Allergy. 2017 Oct;47(10):1239-1245. doi: 10.1111/cea.12972. Epub 2017 Aug 1.

  PMID: 28665534 RESULT

MeSH Terms

Conditions

Asthma

Interventions

indacaterol; Tiotropium Bromide

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Brian Lipworth, MD

  University of Dundee

  PRINCIPAL INVESTIGATOR

• Arvind Deva Manoharan, MBChB

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Allergy and Pulmonology

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 17, 2014
• Study Start: February 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

GB (1)