Clinical trial NCT02279329: Longitudinal Study of Helium-3 and Xenon-129 Magnetic Resonance Imaging
Official title: Longitudinal Study of 3He and 129Xe Magnetic Resonance Imaging in Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: COPD
Bronchiectasis
Lead sponsor: Western University, Canada
Sponsor class: OTHER
Collaborators: name: London Health Sciences Centre
First posted: 2014-10-31
Enrollment: 200
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Subjects male and female aged 50-85 with a clinical diagnosis of chronic obstructive pulmonary disease (COPD) or Bronchiectasis, or those with ≥ 10 pack/years smoking history will be imaged with CT and MRI for the development of tools to quantify and validate longitudinal in vivo magnetic resonance imaging phenotypes of COPD and Bronchiectasis.

Detailed description: COPD patients will be stratified into four groups: Gold Stage 0, Gold Stage I, Gold Stage II, and Gold Stage III. During a single 2-2 ½ hour visit, patient subjects will perform some or all of: 1) spirometry pre-and-post salbutamol and plethysmography, Lung Clearance Index, Airway Oscillometry (Airwave Oscillometry measures the mechanics of the respiratory system by superimposing a gentle multi-frequency airwave onto the patient's respiratory airflow. Measurements take no longer than 16 seconds and the patient simply breathes normally into a disposable mouthpiece for the duration of the test.) 2) 6MWT (including Borg questionnaire pre-and post-walk), 3) health status evaluation using a self-administered SGRQ and MMRC (Modified Medical Research Council dyspnea scale) 4) CT, and, 5) 3He MRI.

Subjects will first provide written informed consent and then be screened for MRI compatibility and will complete: 1) Spirometry pre-salbutamol, SGRQ after inhaling 2-4 puffs (200-400μg) of the short-acting bronchodilator (eg. Salbutamol), 2) MRI, 3) CT. (Subjects will be taken by wheelchair to and from University Hospital, LHSC to decrease the potential for dynamic hyperinflation), 4) plethysmography and spirometry within 1 ½ hours of salbutamol. Vital signs will be performed. Because it is impossible to schedule imaging at the same time-point post-bronchodilator, subjects will be randomized to MR or CT 30 minutes post-salbutamol (1:1 ratio), to minimize bias.

Eligibility criteria: Inclusion Criteria:

* Subjects male and female aged 50-85 with either A) a clinical diagnosis of COPD or Bronchiectais or B) \>10 pack/year smoking history
* Subject understands the study procedures and is willing to participate in the study as indicated by signature on the informed consent
* Subject must be able to perform a breathhold for 16s.
* Subject is judged to be in otherwise stable health on the basis of medical history
* Subject is ambulatory and can perform the 6MWT
* 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.)
* FEV1 \>25% predicted
* FVC \> 25% predicted and \>0.5L

Exclusion Criteria:

* Patient 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 has a daytime room air oxygen saturation \<90% while lying supine.
* Patient is unable to perform spirometry or plethysmography maneuvers
* Patient is pregnant
* 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.
* 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.)

Primary outcomes:
measure: Ventilation Defect Percent (VDP)
timeFrame: 3 years
measure: Apparent Diffusion Coefficients (ADC)
timeFrame: 3 years
Secondary outcomes:
measure: Six Minute Walk Distance (6MWD)
timeFrame: 3 years
measure: St. George's Respiratory Questionnaire (SGRQ)
timeFrame: 3 years
measure: Spirometry
timeFrame: 3 years
Other outcomes:
Locations:
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
References:
citation: Salerno M, de Lange EE, Altes TA, Truwit JD, Brookeman JR, Mugler JP 3rd. Emphysema: hyperpolarized helium 3 diffusion MR imaging of the lungs compared with spirometric indexes--initial experience. Radiology. 2002 Jan;222(1):252-60. doi: 10.1148/radiol.2221001834.
citation: Evans A, McCormack D, Ouriadov A, Etemad-Rezai R, Santyr G, Parraga G. Anatomical distribution of 3He apparent diffusion coefficients in severe chronic obstructive pulmonary disease. J Magn Reson Imaging. 2007 Dec;26(6):1537-47. doi: 10.1002/jmri.21205.
citation: Mathew L, Evans A, Ouriadov A, Etemad-Rezai R, Fogel R, Santyr G, McCormack DG, Parraga G. Hyperpolarized 3He magnetic resonance imaging of chronic obstructive pulmonary disease: reproducibility at 3.0 tesla. Acad Radiol. 2008 Oct;15(10):1298-311. doi: 10.1016/j.acra.2008.04.019.
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: MacNeil JL, Capaldi DPI, Westcott AR, Eddy RL, Barker AL, McCormack DG, Kirby M, Parraga G. Pulmonary Imaging Phenotypes of Chronic Obstructive Pulmonary Disease Using Multiparametric Response Maps. Radiology. 2020 Apr;295(1):227-236. doi: 10.1148/radiol.2020191735. Epub 2020 Feb 25.