Clinical trial NCT02263794: Hyperpolarized Magnetic Resonance Imaging in Asthma Pre- and Post-Bronchial Thermoplasty
Official title: Hyperpolarized Magnetic Resonance Imaging in Asthma Pre- and Post-Bronchial Thermoplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: Bronchial Thermoplasty
Lead sponsor: Western University, Canada
Sponsor class: OTHER
Collaborators: name: McMaster University
First posted: 2014-10-13
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients in London and Hamilton with severe asthma who are deemed eligible by a respirologist to undergo bronchial thermoplasty treatment will be randomized to image-guided or conventional bronchial thermoplasty using hyperpolarized noble gas imaging.

Detailed description: This is a one year, single centre randomized controlled trial. Subjects will be identified through the London Asthma Centre located at St. Joseph's Hospital and from Hamilton at St. Joseph's Healthcare, and will be given a letter of information for the study. The study will only recruit subjects with asthma who are undergoing BT as part of their normal clinical care and asthma treatment plan. Those interested will sign the consent form at the clinic.

Bronchial thermoplasty (BT) is a novel FDA approved outpatient asthma treatment procedure which aims to "cure" symptoms by permanently reducing airway smooth muscle mass in the lobar and segmental bronchi. Under local anesthetic, radiofrequency energy is delivered to warm the airway wall to 65 degrees celcius. The effect of this procedure is a reduction in airway smooth muscle mass in the treated airways resulting in a reduced potential for bronchoconstriction.

Fourteen asthma patients will be enrolled in the study and each subject will visit the centre on five occasions (three pre-treatment visits and two post-treatment visits). We will evaluate pre-therapy optimization using inflammometry, pre-therapy ventilation defect reproducibility and BT treatment effects (pre-treatment visit 1= 5±2 days pre-optimization, pre-treatment visit 2 = 15±7 days pre-BT, pre-treatment visit 3 = 5±2 days pre-BT, post-treatment visit 4=6 weeks post-BT, post treatment visit 5 = 6 months post-BT). At pre-treatment visit 1, patients will be randomized to image-guided or conventional therapy. For all subjects, at all visits, spirometry, plethysmography and 3He and/or 129Xe MRI will be performed. Methacholine challenge (MCh) will be performed (for those subjects with FEV1 \>60%) at pre-treatment visit 3 and post-treatment visit 4 with spirometry and MRI performed pre- and post-MCh. Pre-treatment visit 3 will include a low-dose thoracic CT that will be used to generate a detailed 3D model of the airway tree. MRI will be co-registered to the CT with 3D airway rendering to enable spatial comparisons between ventilation defects and airways.

All subjects will also complete bi-weekly and weekly quality of life questionnaires. Self-reported data will be uploaded by each subject monthly to our website using a confidential and password protected upload.

MRI of the lungs will be performed using an inhaled contrast agent: either Hyperpolarized Helium-3 or Hyperpolarized Xenon-129. Participants will inhale the hyperpolarized gas and perform a breathhold for up to 16 seconds. Two different types of images will be acquired in the coronal plain during each visit: 1) 1H thoracic cavity, and 2) 3He and/or 129Xe static ventilation. Respiration and oxygen saturation will be monitored throughout the imaging session.

Eligibility criteria: Inclusion Criteria:

* Subject understands the study procedures and is willing to participate in the study as indicated by signature on the informed consent
* Male and female aged 18-60 years of age with a clinical diagnosis of asthma, as per:

  * Beta-agonist reversibility of FEV1\>12%, OR
  * Methacholine FEV1 PC20 ≤ 8 mg/ml if not receiving ICS or ≤ 16mg/ml if receiving an ICS.
* Subject has asthma and is taking regular maintenance medication for the past 12 months that includes:

  * Inhaled corticosteroid (ICS)
  * Long-acting beta agonist (LABA)
  * Other asthma medication such as leukotriene modifier, or anti-IgE, are acceptable
* FEV1 \> 50%pred pre-bronchodilator
* Subject assigned by the clinical team to receive bronchial thermoplasty as part of their asthma treatment plan
* Subject is a non-smoker for 1 year or greater (if former smoker less than 10 pack years total smoking history).
* Subject able to perform reproducible pulmonary function testing (i.e., the 3 best acceptable spirograms have FEV1 values that do not vary more than 5% of the largest value or more than 100 ml, whichever is greater.)
* Subject is judged to be in otherwise stable health on the basis of medical history

Exclusion Criteria:

* Subject is, in the opinion of the investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand the written material
* Subject is unable to perform spirometry or plethysmography maneuvers
* Subject is pregnant
* Recent (within 4 weeks of BL Visit 1) or current asthma exacerbation and/or respiratory tract infection
* Subject has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants.) (At the discretion of the MRI Technologist/3T Manager)
* In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia.

Primary outcomes:
measure: Whole lung and lobe specific ventilation defect percent (VDP) as measured by 3He or 129Xe
timeFrame: 48 +/- 2 weeks post bronchial thermoplasty treatment
Secondary outcomes:
measure: Pulmonary function measurements
timeFrame: 48 +/- 2 weeks post bronchial thermoplasty
measure: Quality of Life questionnaires
timeFrame: 48 +/- 2 weeks post bronchial thermoplasty
measure: Dyspnea Scales
timeFrame: 48 +/- 2 weeks post bronchial thermoplasty
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: Robarts Research Institute; The University of Western Ontario; London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Robarts Research Institute, The University of Western Ontario
name: Grace E Parraga, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: London Health Sciences Centre
name: David G McCormack, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Janssen LJ. Airway smooth muscle as a target in asthma and the beneficial effects of bronchial thermoplasty. J Allergy (Cairo). 2012;2012:593784. doi: 10.1155/2012/593784. Epub 2012 Sep 16.
citation: Pavord ID, Cox G, Thomson NC, Rubin AS, Corris PA, Niven RM, Chung KF, Laviolette M; RISA Trial Study Group. Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma. Am J Respir Crit Care Med. 2007 Dec 15;176(12):1185-91. doi: 10.1164/rccm.200704-571OC. Epub 2007 Sep 27.
citation: Capaldi DPI, Guo F, Xing L, Parraga G. Pulmonary Ventilation Maps Generated with Free-breathing Proton MRI and a Deep Convolutional Neural Network. Radiology. 2021 Feb;298(2):427-438. doi: 10.1148/radiol.2020202861. Epub 2020 Dec 8.
citation: Svenningsen S, Nair P, Guo F, McCormack DG, Parraga G. Is ventilation heterogeneity related to asthma control? Eur Respir J. 2016 Aug;48(2):370-9. doi: 10.1183/13993003.00393-2016. Epub 2016 May 12.