The Protective Potential of Exercise Training on the Cardiopulmonary Morbidity After COVID-19

Rigshospitalet, Denmark28 enrolled

Overview

40 COVID-19 survivors that have been discharged from the hospital will be included in this investigator-blinded randomised study with a 12-week exercise intervention. Patients will be 1:1 block-randomised by sex to either a supervised high intensity interval-based exercise group or standard care (control group).

40 patients will be recruited and undergo baseline testing, including examination, biochemistry, ECG, DXA, OGTT, Pulmonary function, VO2max, RM, plasma volume, AX3, CGM, echocardiography, cardiac MRI. After baseline testing, participants will be randomly allocated into one group receiving standard of care (control group) or a group performing supervised high-intensity interval training three times a week over a period of 12 weeks. The randomization procedure involves a computer-generated block randomization schedule in a ratio of 1:1 stratified by sex by an independent person. Following the 12-week intervention period, both groups will complete a series of follow-up tests (as baseline testing). A 1-year follow-up experimental day is also planned in order to evaluate fitness, cardiac and pulmonary structure and function.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

SINGLE

Enrollment

Conditions

COVID-19, SARS-CoV2

Interventions

High intensity interval trainingBEHAVIORAL

12 weeks of high intensity interval training on exercise bike for 38 minutes 3 times a week

Standard careBEHAVIORAL

standard care after discharge from hospital (control group)

Eligibility

Sex: ALLMin age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 40 years * A laboratory-confirmed initial positive test followed by one negative tests of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ≤ 6 months after hospital discharge * ≤10 L oxygen requirement during hospitalization Exclusion Criteria: * Present atrial fibrillation * Diagnosed with acute myocarditis * Health conditions that prevent participating in the exercise intervention * Patients who cannot undergo MR scans (e.g. kidney disease or metallic implants) * Treatment with IL-6 receptor antagonists (tocilizumab, kevzara) within the last month due to drug interference with the cardiopulmonary exercise adaptations.

Locations (1)

Rigshospitalet

Copenhagen, Denmark

Outcomes

Primary Outcomes

Change in left ventricular mass

measured by MRI scan

Time frame: Through study completion, an average of 12 months

Change in right ventricular volume

measured by MRI scan

Time frame: Through study completion, an average of 12 months

Secondary Outcomes

Stroke volume

Structural cardiac parameter: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

end-diastolic volume

Structural cardiac parameter: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

IVS thickness (intact ventricular septum)

Structural cardiac parameter: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

LVID (left ventricular internal dimensions)

Structural cardiac parameter: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

PWT (posterior wall thickness)

Structural cardiac parameter: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

LAVI (left atrial volume index)

Structural cardiac parameter: measured by MRI scan and echocardiography

Data from ClinicalTrials.gov

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Time frame: Through study completion, an average of 12 months

LVEF

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

Global longitudinal strain

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

E/A ratio

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

E´

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

RV volumes

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

RVEF

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

TAPSE

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

Change in maximal tricuspid regurgitation velocity and pressure gradient

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

RV s´

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

Peak E velocity

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

Peak A velocity

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

Septal e´

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

Lateral e´

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

E/e´ septal

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

E/e´ lateral

Functional cardiac parameters: measured by MRI scan and echocardiography

Time frame: Through study completion, an average of 12 months

Cardiac inflammation

measured with gadolinium and MRI scan

Time frame: Through study completion, an average of 12 months

Vascular dysfunction

measured with gadolinium and MRI scan

Time frame: Through study completion, an average of 12 months

Extracellular volume

measured with gadolinium and MRI scan

Time frame: Through study completion, an average of 12 months

Diffuse fibrotic changes

measured with gadolinium and MRI scan

Time frame: Through study completion, an average of 12 months

Blood and plasma volume

changes

Time frame: Through study completion, an average of 12 months

Body composition analysis measured with DXA

easuring Lean mass, Fat mass and BMD

Time frame: Through study completion, an average of 12 months

Cardiorespiratory fitness

Measured with an incremental VO2 protocol on exercise bike

Time frame: Through study completion, an average of 12 months

Dynamic spirometri

Pulmonary function testing

Time frame: Through study completion, an average of 12 months

Whole body plethymography

Pulmonary function testing

Time frame: Through study completion, an average of 12 months

Diffusion capacity

Pulmonary function testing

Time frame: Through study completion, an average of 12 months

Oral glucose tolerance test

75g of glucose taken while fasting

Time frame: 2 hours at baseline and same after intervention

Continuous glucose monitoring

Three days of continuous glucose monitoring (CGM) is performed using enzyme-coated electrodes (iPro MMT- 7745WW; Medtronic, Northridge, CA, USA) placed subcutaneously in the abdominal wall. For calibration of the CGM system, finger-prick blood glucose measurements are performed by the participant four times daily.

Time frame: 3 days at baseline and same after intervention

Axial accelerometer-based physical activity monitors

Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 4-day period

Time frame: 4 days at baseline and same after intervention

Blood samples analysed for markers related to low grade inflammation

Including high-sensitivity C-reactive protein, tumour necrosis factor-α, IL-1RA, interferon-γ and interleukins (IL-6, IL-10 and others) Following an overnight fast (10 hours), blood samples, are collected and processed by a trained laboratory technician and analysed according to standard procedures. Plasma is stored at - 80 °C prior to analysis.

Time frame: Through study completion, an average of 12 months

Blood samples analysed for markers related to cardiometabolic biomarkers.

Including total troponins, D-dimer, creatinine kinase, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, glycated haemoglobin, fasting insulin, fasting plasma glucose, pro-brain natriuretic peptide, haematology, electrolytes and liver and renal status. Following an overnight fast (10 hours), blood samples, are collected and processed by a trained laboratory technician and analysed according to standard procedures. Plasma is stored at - 80 °C prior to analysis.

Time frame: Through study completion, an average of 12 months

SF-36, King´s Brief Interstitial Lung Disease Questionnaire, Post-COVID-19 Functional Status

Questionnaires on quality of life will be filled in on baseline and after the intervention

Time frame: Through study completion, an average of 12 months

King´s Brief Interstitial Lung Disease Questionnaire

Questionnaires on quality of life will be filled in on baseline and after the intervention

Time frame: Through study completion, an average of 12 months

Post-COVID-19 Functional Status

Questionnaires on quality of life will be filled in on baseline and after the intervention

Time frame: Through study completion, an average of 12 months