Lung Structure-Function In Survivors of Mild and Severe COVID-19 Infection

Covid19 Clinical Trial

— LIVECOVIDFREE  

Official title:

Lung Structure-Function In SurVivors of Mild and SEvere COVID-19 Infection: 129Xe MRI and CT For Rapid Evaluations and NExt-wave Healthcare Planning

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04584671
• Other study ID #: ROB0050
• Status: Active, not recruiting
• Start date: January 1, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: April 2024
• Source: Western University, Canada
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a longitudinal study of the long-term impact of COVID-19 on the lungs. Participants will be followed over a period of up to 4 years and impacts of COVID-19 on the lungs will be measured with magnetic resonance imaging (MRI) using hyperpolarized xenon-129, pulmonary function tests, exercise capacity, computed tomography imaging and questionnaires.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19

Intervention

Diagnostic Test:
• Hyperpolarized Xenon-129 MRI of the lungs
Participants will be imaged using MRI using hyperpolarized xenon-129 gas as a contrast gas
• Computed Tomography (CT)
Participants will undergo a CT scan of the thoracic cavity
• Pulmonary Function Tests (PFT)
Participants will have their lung function evaluated using PFT
• Six Minute Walk Test (6MWT)
Participants will perform the six minute walk test as a measure of exercise capacity
• Sputum analysis
Participants will provide a sputum sample that will be analysed for eosinophils
• Blood analysis
Participants will have their blood drawn and analysed for eosinophil count.

Other:
• Questionnaires
Participants will complete questionnaires to assess activity related dyspnea, respiratory symptoms and health status impairment and respiratory related quality of life.

Locations

Country	Name	City	State
Canada	Department of Medicine (Respirology), McMaster University	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Western University, Canada	London Health Sciences Centre

Country where clinical trial is conducted

Canada, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by VDP.	Measured using 129-Xenon MRI ventilation defect percent	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FEV1.	Measured using forced expiratory volume in one second (FEV1)	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FVC.	Measured using forced vital capacity (FVC)	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by TLC.	Measured using total lung capacity (TLC)	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FRC.	Functional residual capacity (FRC)	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by RV.	Measured using residual volume (RV)	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FOT.	Measured using forced oscillation technique (FOT)	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by LCI.	Measured using lung clearance index (LCI)	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by FeNO.	Measured using Fractional Exhaled Nitric Oxide (FeNO).	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by exercise capacity.	Exercise capacity measured by six-minute walk test	1 year
Primary	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	Measured using the baseline dyspnea index questionnaire.	1 year
Primary	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.	Measured using the modified medical research council (mMRC) dyspnea scale questionnaire.	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by CAT.	Measured using the COPD assessment test (CAT).	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by SGRQ.	Measured using the St. George's respiratory questionnaire (SGRQ).	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by IPAQ.	Measured using the International Physical Activity Questionnaire (IPAQ).	1 year
Primary	Determine long-term respiratory impairment in COVID-19 survivors who did and did not require hospitalization at one year as measured by eosinophil count.	Measured using blood and sputum eosinophil count.	1 year
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by VDP.	Measured using 129-Xenon MRI ventilation defect percent	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FEV1.	Measured using forced expiratory volume in one second (FEV1).	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FVC.	Measured using forced vital capacity (FVC)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by TLC.	Measured using total lung capacity (TLC)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FRC.	Measured using functional residual capacity (FRC)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by RV.	Measured using residual volume (RV)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FOT.	Measured using forced oscillation technique (FOT).	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by LCI.	Measured using lung clearance index (LCI)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by FeNO.	Measured using Fractional Exhaled Nitric Oxide (FeNO)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by exercise capacity.	Exercise capacity measured by six-minute walk test	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the baseline dyspnea index questionnaire.	Measured using the baseline dyspnea index questionnaire.	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by the mMRC dyspnea scale questionnaire.	Measured using the modified medical research council (mMRC) dyspnea scale questionnaire	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by CAT.	Measured using the COPD assessment test (CAT)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by SGRQ.	Measured using the St. George's respiratory questionnaire (SGRQ)	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by IPAQ.	Measured using the International Physical Activity Questionnaire (IPAQ).	within 3 months post COVID-19 infection recovery
Secondary	Determine the clinical, structural, physiologic, and imaging biomarkers within 3 months post COVID-19 infection recovery as measured by eosinophil count..	Measured using blood and sputum eosinophil count.	within 3 months post COVID-19 infection recovery
Secondary	Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by sex.	Evaluated by assessing different genders.	up to 4 years
Secondary	Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by age.	Evaluated by assessing different age groups.	up to 4 years
Secondary	Determine if COVID-19-induced respiratory impairment and predictors of respiratory impairment differ by smoking history measured in pack-years.	Evaluated by assessing smoking history measured in pack-years.	up to 4 years