Evaluation of Triple Therapy Using Magnetic Resonance Imaging in Asthma

Summary

The purpose of this study is to evaluate the effectiveness of treatment with triple therapy an inhaler that contains three types of asthma medications, on participants with poorly controlled asthma. The triple therapy medication contains fluticasone furoate, an inhaled corticosteroid (ICS) which reduces inflammation in the lungs; umeclidinium (UMEC), a long-acting muscarinic antagonist (LAMA), a medication which helps open up the airways; and vilanterol (VI), a long-acting beta2-adrenergic agonist (LABA) which also helps open up airways, delivered in a single daily inhalation via an Ellipta inhaler. The Investigators will evaluate lung structure and function using magnetic resonance imaging (MRI). Participants will inhale xenon gas before an MRI image of their lungs is taken. Using a special technique xenon is visible in MRI images, so this lets us see how air spreads in the lungs. In healthy lungs, the gas fills the lungs evenly, but in unhealthy lungs, the gas may fill the lungs unevenly and they will appear patchy. The patchy areas are called ventilation defects. A CT of the chest will be done to assess the structure of the lungs. The Investigators will also be using lung function testing and questionnaires to compare them to MRI ventilation defect measurements.

Timeline

Start

2022-08-08

Primary completion

2023-08-25

Completion

2025-12

Publications

• Background Kerwin E, Pascoe S, Bailes Z, Nathan R, Bernstein D, Dahl R, von Maltzahn R, Robbins K, Fowler A, Lee L. A phase IIb, randomised, parallel-group study: the efficacy, safety and tolerability of once-daily umeclidinium in patients with asthma receiving inhaled corticosteroids. Respir Res. 2020 Jun 12;21(1):148. doi: 10.1186/s12931-020-01400-5.
• Background Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention: Updated 2017. (2017).
• Background Dreher M, Muller T. Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid. Tuberc Respir Dis (Seoul). 2018 Jan;81(1):1-5. doi: 10.4046/trd.2017.0102. Epub 2017 Dec 13.
• Background Walford HH, Doherty TA. Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy. 2014 Apr 11;7:53-65. doi: 10.2147/JAA.S39119. eCollection 2014.
• Background de Groot JC, Ten Brinke A, Bel EH. Management of the patient with eosinophilic asthma: a new era begins. ERJ Open Res. 2015 Sep 23;1(1):00024-2015. doi: 10.1183/23120541.00024-2015. eCollection 2015 May.
• Background Fain S, Schiebler ML, McCormack DG, Parraga G. Imaging of lung function using hyperpolarized helium-3 magnetic resonance imaging: Review of current and emerging translational methods and applications. J Magn Reson Imaging. 2010 Dec;32(6):1398-408. doi: 10.1002/jmri.22375.
• Background Altes TA, Powers PL, Knight-Scott J, Rakes G, Platts-Mills TA, de Lange EE, Alford BA, Mugler JP 3rd, Brookeman JR. Hyperpolarized 3He MR lung ventilation imaging in asthmatics: preliminary findings. J Magn Reson Imaging. 2001 Mar;13(3):378-84. doi: 10.1002/jmri.1054.
• Background Aysola R, de Lange EE, Castro M, Altes TA. Demonstration of the heterogeneous distribution of asthma in the lungs using CT and hyperpolarized helium-3 MRI. J Magn Reson Imaging. 2010 Dec;32(6):1379-87. doi: 10.1002/jmri.22388.
• Background Svenningsen S, Kirby M, Starr D, Coxson HO, Paterson NA, McCormack DG, Parraga G. What are ventilation defects in asthma? Thorax. 2014 Jan;69(1):63-71. doi: 10.1136/thoraxjnl-2013-203711. Epub 2013 Aug 16.
• Background Campana L, Kenyon J, Zhalehdoust-Sani S, Tzeng YS, Sun Y, Albert M, Lutchen KR. Probing airway conditions governing ventilation defects in asthma via hyperpolarized MRI image functional modeling. J Appl Physiol (1985). 2009 Apr;106(4):1293-300. doi: 10.1152/japplphysiol.91428.2008. Epub 2009 Feb 12.
• Background Costella S, Kirby M, Maksym GN, McCormack DG, Paterson NA, Parraga G. Regional pulmonary response to a methacholine challenge using hyperpolarized (3)He magnetic resonance imaging. Respirology. 2012 Nov;17(8):1237-46. doi: 10.1111/j.1440-1843.2012.02250.x.
• Background Kruger SJ, Niles DJ, Dardzinski B, Harman A, Jarjour NN, Ruddy M, Nagle SK, Francois CJ, Sorkness RL, Burton RM, Munoz del Rio A, Fain SB. Hyperpolarized Helium-3 MRI of exercise-induced bronchoconstriction during challenge and therapy. J Magn Reson Imaging. 2014 May;39(5):1230-7. doi: 10.1002/jmri.24272. Epub 2013 Sep 4.
• Background Samee S, Altes T, Powers P, de Lange EE, Knight-Scott J, Rakes G, Mugler JP 3rd, Ciambotti JM, Alford BA, Brookeman JR, Platts-Mills TA. Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: assessment of response to methacholine and exercise challenge. J Allergy Clin Immunol. 2003 Jun;111(6):1205-11. doi: 10.1067/mai.2003.1544.
• Background Tzeng YS, Lutchen K, Albert M. The difference in ventilation heterogeneity between asthmatic and healthy subjects quantified using hyperpolarized 3He MRI. J Appl Physiol (1985). 2009 Mar;106(3):813-22. doi: 10.1152/japplphysiol.01133.2007. Epub 2008 Nov 20.

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Indications