- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04584671
Lung Structure-Function In Survivors of Mild and Severe COVID-19 Infection (LIVECOVIDFREE)
Lung Structure-Function In SurVivors of Mild and SEvere COVID-19 Infection: 129Xe MRI and CT For Rapid Evaluations and NExt-wave Healthcare Planning
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a multisite longitudinal study of the long-term lung health impact of COVID-19 using hyperpolarized xenon-129 (129Xe) magnetic resonance imaging (MRI) over a period of up to 4 years.
In total 200 participants age ≥ 18 and <80 years who experienced a documented case of COVID-19 (documented by positive COVID-19 test and/or clinical history) will be screened and recruited if they meet all inclusion criteria at the 5 participating sites. Participants will be grouped in mild or severe COVID-19 infection (100 in each group) including 50 with symptoms and at least 50 participants who were hospitalized with COVID-19 infection, all of whom are within 3 months post recovery and non-infectious. Participants will attend up to 5 study visits over the 4 year period. (Visit 1 within 3 months post-COVID-19 recovery, Visit 2 at 24 ± 4 weeks, Visit 3 at 48 ± 4 weeks, Visit 4 at 78 ± 4 weeks, Visit 5 at 200 ± 16 weeks)
At all visits, participants will complete 129Xe MRI, questionnaires (St. George's Respiratory Questionnaire, COPD Assessment Test, Modified Medical Research Council Dyspnea Scale, Modified Borg Scale Breathlessness and Fatigue Questionnaire, Baseline Dyspnea Index Questionnaire and International Physical Activity Questionnaire), pulmonary function tests (Spirometry, Plethysmography, Forced Oscillation Technique, Fractional Exhaled Nitric Oxide, and Multiple Breath Nitrogen Washout), blood and sputum analysis, exercise testing (six-minute walk test). At Visit 1, participants will also complete computed tomography imaging at University Hospital, London Health Sciences Centre. Visits 2 and 4 have the option of being completed over the phone, in which case only questionnaires will be completed. Visit 5 is an optional 4-year follow-up.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Grace E Parraga, PhD
- Phone Number: (519) 931-5265
- Email: gparraga@robarts.ca
Study Contact Backup
- Name: Angela Wilson, RRT
- Phone Number: 24197 519-931-5777
- Email: awilson@robarts.ca
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada
- Department of Medicine (Respirology), McMaster University
-
Contact:
- Sarah Svenningsen, PhD
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Participants who are fluent in English reading, understanding and speaking
- Written informed consent must be directly obtained from legally competent participants before any study-related assessment is performed.
- Male and female participants ≥ 18 years and < 80 years.
- Participant experienced a documented case (documented by positive COVID-19 test and/or clinical history) of mild or severe COVID-19 infection.
- Participants are within 3 months post-recovery.
- 100 participants will have had mild symptoms.
- 100 participants will have had severe symptoms, at least 50 of whom were hospitalized.
Exclusion Criteria:
- Participants meeting contraindications for undergoing an MRI such as participants with MRI-sensitive implants, tattoos with MRI-sensitive dye and severe claustrophobia.
- Participant is, in the opinion of the Investigator, mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand written material.
- Participant is unable to perform spirometry or plethysmography maneuvers.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Mild COVID-19 Infection Group
100 participants age ≥ 18 and <80 years who experienced a documented case (documented by positive COVID-19 test and/or clinical history) of mild COVID-19 infection, all of whom are within 3 months post recovery and non-infectious.
|
Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas
Other Names:
Participants will undergo a CT scan of the thoracic cavity
Other Names:
Participants will have their lung function evaluated using PFT
Other Names:
Participants will perform the six minute walk test as a measure of exercise capacity
Other Names:
Participants will provide a sputum sample that will be analysed for eosinophils
Participants will have their blood drawn and analysed for eosinophil count.
Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.
|
Severe COVID-19 Infection Group
100 participants age ≥ 18 and <80 years who experienced a documented case (documented by positive COVID-19 test and/or clinical history) of severe COVID-19 infection, including at least 50 participants who were hospitalized with COVID-19 infection, all of whom are within 3 months post recovery and non-infectious.
|
Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas
Other Names:
Participants will undergo a CT scan of the thoracic cavity
Other Names:
Participants will have their lung function evaluated using PFT
Other Names:
Participants will perform the six minute walk test as a measure of exercise capacity
Other Names:
Participants will provide a sputum sample that will be analysed for eosinophils
Participants will have their blood drawn and analysed for eosinophil count.
Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by VDP.
Time Frame: 1 year
|
Measured using 129-Xenon MRI ventilation defect percent
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FEV1.
Time Frame: 1 year
|
Measured using forced expiratory volume in one second (FEV1)
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FVC.
Time Frame: 1 year
|
Measured using forced vital capacity (FVC)
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by TLC.
Time Frame: 1 year
|
Measured using total lung capacity (TLC)
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FRC.
Time Frame: 1 year
|
Functional residual capacity (FRC)
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by RV.
Time Frame: 1 year
|
Measured using residual volume (RV)
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FOT.
Time Frame: 1 year
|
Measured using forced oscillation technique (FOT)
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by LCI.
Time Frame: 1 year
|
Measured using lung clearance index (LCI)
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FeNO.
Time Frame: 1 year
|
Measured using Fractional Exhaled Nitric Oxide (FeNO).
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by exercise capacity.
Time Frame: 1 year
|
Exercise capacity measured by six-minute walk test
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by baseline dyspnea index questionnaire
Time Frame: 1 year
|
Measured using the baseline dyspnea index questionnaire.
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by (mMRC) dyspnea scale questionnaire.
Time Frame: 1 year
|
Measured using the modified medical research council (mMRC) dyspnea scale questionnaire.
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by CAT.
Time Frame: 1 year
|
Measured using the COPD assessment test (CAT).
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by SGRQ.
Time Frame: 1 year
|
Measured using the St. George's respiratory questionnaire (SGRQ).
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by IPAQ.
Time Frame: 1 year
|
Measured using the International Physical Activity Questionnaire (IPAQ).
|
1 year
|
Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by eosinophil count.
Time Frame: 1 year
|
Measured using blood and sputum eosinophil count.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by VDP.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using 129-Xenon MRI ventilation defect percent
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FEV1.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using forced expiratory volume in one second (FEV1).
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FVC.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using forced vital capacity (FVC)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by TLC.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using total lung capacity (TLC)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FRC.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using functional residual capacity (FRC)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by RV.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using residual volume (RV)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FOT.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using forced oscillation technique (FOT).
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by LCI.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using lung clearance index (LCI)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FeNO.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using Fractional Exhaled Nitric Oxide (FeNO)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by exercise capacity.
Time Frame: within 3 months post COVID-19 infection recovery
|
Exercise capacity measured by six-minute walk test
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the baseline dyspnea index questionnaire.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using the baseline dyspnea index questionnaire.
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the mMRC dyspnea scale questionnaire.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using the modified medical research council (mMRC) dyspnea scale questionnaire
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by CAT.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using the COPD assessment test (CAT)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by SGRQ.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using the St. George's respiratory questionnaire (SGRQ)
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by IPAQ.
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using the International Physical Activity Questionnaire (IPAQ).
|
within 3 months post COVID-19 infection recovery
|
Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by eosinophil count..
Time Frame: within 3 months post COVID-19 infection recovery
|
Measured using blood and sputum eosinophil count.
|
within 3 months post COVID-19 infection recovery
|
Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by sex.
Time Frame: up to 4 years
|
Evaluated by assessing different genders.
|
up to 4 years
|
Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by age.
Time Frame: up to 4 years
|
Evaluated by assessing different age groups.
|
up to 4 years
|
Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by smoking history measured in pack-years.
Time Frame: up to 4 years
|
Evaluated by assessing smoking history measured in pack-years.
|
up to 4 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Grace E Parraga, PhD, Robarts Research Institute, The University of Western Ontario
Publications and helpful links
General Publications
- Driehuys B, Martinez-Jimenez S, Cleveland ZI, Metz GM, Beaver DM, Nouls JC, Kaushik SS, Firszt R, Willis C, Kelly KT, Wolber J, Kraft M, McAdams HP. Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients. Radiology. 2012 Jan;262(1):279-89. doi: 10.1148/radiol.11102172. Epub 2011 Nov 4.
- Shukla Y, Wheatley A, Kirby M, Svenningsen S, Farag A, Santyr GE, Paterson NA, McCormack DG, Parraga G. Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease. Acad Radiol. 2012 Aug;19(8):941-51. doi: 10.1016/j.acra.2012.03.018. Epub 2012 May 15.
- Schmidt MH, Marshall J, Downie J, Hadskis MR. Pediatric magnetic resonance research and the minimal-risk standard. IRB. 2011 Sep-Oct;33(5):1-6. No abstract available.
- Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
- Oostveen E, MacLeod D, Lorino H, Farre R, Hantos Z, Desager K, Marchal F; ERS Task Force on Respiratory Impedance Measurements. The forced oscillation technique in clinical practice: methodology, recommendations and future developments. Eur Respir J. 2003 Dec;22(6):1026-41. doi: 10.1183/09031936.03.00089403.
- Kirby M, Heydarian M, Svenningsen S, Wheatley A, McCormack DG, Etemad-Rezai R, Parraga G. Hyperpolarized 3He magnetic resonance functional imaging semiautomated segmentation. Acad Radiol. 2012 Feb;19(2):141-52. doi: 10.1016/j.acra.2011.10.007. Epub 2011 Nov 21.
- Owrangi AM, Etemad-Rezai R, McCormack DG, Cunningham IA, Parraga G. Computed tomography density histogram analysis to evaluate pulmonary emphysema in ex-smokers. Acad Radiol. 2013 May;20(5):537-45. doi: 10.1016/j.acra.2012.11.010.
- Pizzichini E, Pizzichini MM, Efthimiadis A, Evans S, Morris MM, Squillace D, Gleich GJ, Dolovich J, Hargreave FE. Indices of airway inflammation in induced sputum: reproducibility and validity of cell and fluid-phase measurements. Am J Respir Crit Care Med. 1996 Aug;154(2 Pt 1):308-17. doi: 10.1164/ajrccm.154.2.8756799.
- McGavin CR, Artvinli M, Naoe H, McHardy GJ. Dyspnoea, disability, and distance walked: comparison of estimates of exercise performance in respiratory disease. Br Med J. 1978 Jul 22;2(6132):241-3. doi: 10.1136/bmj.2.6132.241.
- Jones PW, Harding G, Berry P, Wiklund I, Chen WH, Kline Leidy N. Development and first validation of the COPD Assessment Test. Eur Respir J. 2009 Sep;34(3):648-54. doi: 10.1183/09031936.00102509.
- Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am Rev Respir Dis. 1992 Jun;145(6):1321-7. doi: 10.1164/ajrccm/145.6.1321.
- Matheson AM, McIntosh MJ, Kooner HK, Lee J, Desaigoudar V, Bier E, Driehuys B, Svenningsen S, Santyr GE, Kirby M, Albert MS, Shepelytskyi Y, Grynko V, Ouriadov A, Abdelrazek M, Dhaliwal I, Nicholson JM, Parraga G. Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome. Radiology. 2022 Nov;305(2):466-476. doi: 10.1148/radiol.220492. Epub 2022 Jun 28.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- COVID-19
- Physiological Effects of Drugs
- Central Nervous System Depressants
- Anesthetics, General
- Anesthetics
- Anesthetics, Inhalation
- Xenon
Other Study ID Numbers
- ROB0050
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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