Longitudinal Study of Helium-3 and Xenon-129 Magnetic Resonance Imaging

COPD Clinical Trial

Official title:

Longitudinal Study of 3He and 129Xe Magnetic Resonance Imaging in Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02279329
• Other study ID #: ROB0018
• Status: Recruiting
• Phase: N/A
• Start date: May 2009
• Est. completion date: February 2025

Study information

• Verified date: June 2024
• Source: Western University, Canada
• Contact: Grace E Parraga, PhD
• Phone: 519-931-5265
• Email: gparraga[@]robarts.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Bronchiectasis
• COPD

Intervention

Other:
• Hyperpolarized Helium MRI
Hyperpolarized helium-3 (3He) magnetic resonance imaging (MRI) has recently emerged as another research approach for the non-invasive measurement of lung structure and function, including conduction of gas through airways and into airspaces. Preliminary studies suggest that 3He MRI may be ideally suited for longitudinal COPD research, which is a likely target application of this novel technology. 3He MRI provides a complementary and alternative method for evaluating COPD and may be superior to CT because it allows simultaneous visualization of both airway and airspace structure and function.

Locations

Country	Name	City	State
Canada	Robarts Research Institute; The University of Western Ontario; London Health Sciences Centre	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Dr. Grace Parraga	London Health Sciences Centre

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilation Defect Percent (VDP)	VDP is a widely used noble gas MRI biomarkers that is calculated by normalizing ventilation defect volume to the thoracic cavity	3 years
Primary	Apparent Diffusion Coefficients (ADC)	Diffusion weighted noble gas MRI provides a way to quantify pulmonary microstructure by sensing the movements of inhaled gas atoms. The "apparent" dif fusion coefficient (ADC) during the diffusion time interval can be used to reflect the extent of alveolar restriction of gas atom movements, providing a surrogate measurement of airspace dimensions.	3 years
Secondary	Six Minute Walk Distance (6MWD)	The 6-min walk test (6 MWT) is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes.	3 years
Secondary	St. George's Respiratory Questionnaire (SGRQ)	Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease.	3 years
Secondary	Spirometry	Spirometry is a common office test used to assess how well your lungs work by measuring how much air you inhale, how much you exhale and how quickly you exhale.	3 years