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

Iben Elmerdahl Rasmussen, Frederik Foged, Josephine Bjørn Budde, Rasmus Syberg Rasmussen, Villads Rasmussen, Mark Lyngbæk, Simon Jønck, Rikke Krogh-Madsen, Birgitte Lindegaard, Mathias Ried-Larsen, Peter Godsk Jørgensen, Morten Asp Vonsild Lund, Lars Køber, Niels Vejlstrup, Bente Klarlund Pedersen, Ronan M G Berg, Regitse Højgaard Christensen, Iben Elmerdahl Rasmussen, Frederik Foged, Josephine Bjørn Budde, Rasmus Syberg Rasmussen, Villads Rasmussen, Mark Lyngbæk, Simon Jønck, Rikke Krogh-Madsen, Birgitte Lindegaard, Mathias Ried-Larsen, Peter Godsk Jørgensen, Morten Asp Vonsild Lund, Lars Køber, Niels Vejlstrup, Bente Klarlund Pedersen, Ronan M G Berg, Regitse Højgaard Christensen

Abstract

Introduction: COVID-19 is associated with a marked systemic inflammatory response with concomitant cardiac injury and remodelling, but it is currently unknown whether the latter is reversible. Given that high-intensity interval training (HIIT) is a powerful stimulus to improve cardiorespiratory fitness while also eliciting marked anti-inflammatory effects, it may be an important countermeasure of reducing cardiopulmonary morbidity following COVID-19.

Methods and analysis: 40 COVID-19 survivors who have been discharged from hospital will be included in this investigator-blinded randomised study with a 12-week HIIT intervention. Patients will be 1:1 block-randomised by sex to either a supervised HIIT exercise group or standard care (control group). The main hypothesis is that a 12-week HIIT scheme is a safe way to improve loss of cardiac mass and associated cardiorespiratory fitness, despite hypothesised limited HIIT-induced changes in conventional lung function indices per se. Ultimately, we hypothesise that the HIIT scheme will reduce post-COVID-19 symptoms and improve quality of life.

Ethics and dissemination: This study is approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-20033733, including amendments 75068 and 75799) and registered at ClinicalTrials.gov (NCT04647734, pre-results). The findings will be published in a peer-reviewed journal, including cases of positive, negative and inconclusive results.Trial registration number NCT04549337.

Keywords: COVID-19; cardiology; sports medicine.

Conflict of interest statement

Competing interests: MR-L has received personal lecture fees from Novo Nordisk A/S. PGJ reports honorarium from Novo Nordisk and AstraZeneca. LK reports speaker honorarium from Novo, Novartis, Boehringer and AstraZeneca, unrelated to this manuscript.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study overview and tests. AX3, axial accelerometer-based physical activity monitor; CGM, continuous glucose monitoring; DXA, dual-energy X-ray absorptiometry; echo, echocardiography; examination, health examination; OGTT, oral glucose tolerance test; RM, 1 repetition max; VO2max, maximal oxygen consumption.
Figure 2
Figure 2
Flow chart of patient self-report method for the Post-COVID-19 Functional Status scale.
Figure 3
Figure 3
A 10-item general fatigue questionnaire for assessing both physical and mental fatigue (Fatigue Assessment Scale).
Figure 4
Figure 4
Sample size scenarios. MD, mean difference of change between the intervention groups.

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