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

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).

Study Overview

• Status: Completed
• Conditions: COVID-19, SARS-CoV2
• Intervention / Treatment: Behavioral: High intensity interval training; Behavioral: Standard care

Detailed Description

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
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High intensity interval training; The experimental group will on top of standard care undergo a 12 weeks supervised exercise high intensity interval exercise training on an ergometer bike three times a week for 38 minutes. The specific intervals will be determined from our ongoing pilot study (NCT04549337)	Behavioral: High intensity interval training; 12 weeks of high intensity interval training on exercise bike for 38 minutes 3 times a week
ACTIVE_COMPARATOR: Control group; This group will be allocated to standard care and therefore no supervised exercise regimen.	Behavioral: Standard care; standard care after discharge from hospital (control group)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in left ventricular mass	measured by MRI scan	Through study completion, an average of 12 months
Change in right ventricular volume	measured by MRI scan	Through study completion, an average of 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke volume	Structural cardiac parameter: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
end-diastolic volume	Structural cardiac parameter: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
IVS thickness (intact ventricular septum)	Structural cardiac parameter: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
LVID (left ventricular internal dimensions)	Structural cardiac parameter: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
PWT (posterior wall thickness)	Structural cardiac parameter: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
LAVI (left atrial volume index)	Structural cardiac parameter: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
LVEF	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
Global longitudinal strain	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
E/A ratio	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
E´	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
RV volumes	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
RVEF	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
TAPSE	Functional cardiac parameters: measured by MRI scan and echocardiography	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	Through study completion, an average of 12 months
RV s´	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
Peak E velocity	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
Peak A velocity	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
Septal e´	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
Lateral e´	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
E/e´ septal	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
E/e´ lateral	Functional cardiac parameters: measured by MRI scan and echocardiography	Through study completion, an average of 12 months
Cardiac inflammation	measured with gadolinium and MRI scan	Through study completion, an average of 12 months
Vascular dysfunction	measured with gadolinium and MRI scan	Through study completion, an average of 12 months
Extracellular volume	measured with gadolinium and MRI scan	Through study completion, an average of 12 months
Diffuse fibrotic changes	measured with gadolinium and MRI scan	Through study completion, an average of 12 months
Blood and plasma volume	changes	Through study completion, an average of 12 months
Body composition analysis measured with DXA	easuring Lean mass, Fat mass and BMD	Through study completion, an average of 12 months
Cardiorespiratory fitness	Measured with an incremental VO2 protocol on exercise bike	Through study completion, an average of 12 months
Dynamic spirometri	Pulmonary function testing	Through study completion, an average of 12 months
Whole body plethymography	Pulmonary function testing	Through study completion, an average of 12 months
Diffusion capacity	Pulmonary function testing	Through study completion, an average of 12 months
Oral glucose tolerance test	75g of glucose taken while fasting	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.	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	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.	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.	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	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	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	Through study completion, an average of 12 months

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Regitse Christensen, MD, PhD, Center For Physical Activity Research, Rigshospitalet

Publications and helpful links

General Publications

• Rasmussen IE, Foged F, Bjorn Budde J, Rasmussen RS, Rasmussen V, Lyngbaek M, Jonck S, Krogh-Madsen R, Lindegaard B, Ried-Larsen M, Jorgensen PG, Lund MAV, Kober L, Vejlstrup N, Pedersen BK, Berg RMG, Christensen RH. Protective potential of high-intensity interval training on cardiac structure and function after COVID-19: protocol and statistical analysis plan for an investigator-blinded randomised controlled trial. BMJ Open. 2021 Nov 18;11(11):e048281. doi: 10.1136/bmjopen-2020-048281.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2021
• Primary Completion (ACTUAL): February 1, 2022
• Study Completion (ACTUAL): February 10, 2022

Study Registration Dates

• First Submitted: November 25, 2020
• First Submitted That Met QC Criteria: November 27, 2020
• First Posted (ACTUAL): December 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 8, 2022
• Last Update Submitted That Met QC Criteria: June 3, 2022
• Last Verified: June 1, 2022

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
• Other Study ID Numbers: H-20033733 v.2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No