Feasibility and Safety of High-intensity Exercise Training in Patients Surviving COVID-19

Study Overview
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Brief Summary
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This current protocol encompasses an investigator-blinded randomized exercise intervention in 10 COVID-19 survivors that have been discharged from hospital. The subjects will be randomized to perform three different exercise training protocols in a random order. The aim is to clarify the feasibility and safety of three training protocols in COVID-19 survivors. The hypothesis is that patients surviving COVID-19 will be able to comply to all training protocols.

Detailed Description
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The study is a randomized crossover trial testing the feasibility and safety of three different training protocols in 10 COVID-19 survivors that have been discharged from hospital. The subjects will be randomized to perform three different exercise training protocols in a random order. The aim is to clarify the feasibility and safety of three training protocols in COVID-19 survivors. The hypothesis is that patients surviving COVID-19 will be able to comply to all training protocols. The study consists of 4 visits with 1 baseline session (a medical screening and fitness test) and 3 different training sessions. Each training is separated by 1-week washout, to account for potential confounding by leisure activity performed just before the training, patients will be wearing activity watches (Polar). Feasibility and safety evaluation will be based on 1) how tolerable and enjoyable the training was based on a subjective questionnaire (Likert Scale) 2) compliance to the prescribed exercise protocol with regard to duration and intensity and 3) experienced side effects.

Official Title
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Investigator-blinded Randomized Controlled Trial Examining the Safety and Feasibility of Different Exercise Training Programs in Patients Who Have Survived COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Behavioral: Exercise training


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study uses a randomized crossover trial testing the feasibility of 3 different training protocols.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4X4<br>An exercise training protocol with a duration of 38 minutes consisting of a 10 minutes warm up with a heart rate of 60-70% of HRmax followed by 4 intervals of 4 minutes at an intensity that will induce at least 85% of HRmax (we will start with 75% of watt max). Each interval is separated by 3-minute active pauses, biking at 50-70% of HRmax. Following this a 3-minute cooldown (at warm up intensity) will be performed. | Behavioral: Exercise training<br>* Feasibility and safety of 3 different training protocols will be tested. Therefore the intervention is three different exercise protocols (4X4, 6X1, and 10-20-30). The exercise workload is set according to the patients HRmax or wattmax from a VO2max test at the baseline testing. All training protocols have a duration of 38 minutes and start with a 10-minute warm up and a 3-7-minute cool-down period. The intervals in the training protocols are interspersed with a 3-minute active rest. Therefore the three exercise protocols are matched on duration, and they all fall within the category of high-intensity-interval training. The accumulated time spend with a heart rate >85% of HR max will be evaluated to determine the intensity.<br>|
| Active Comparator: 6X1<br>An exercise training protocol with a duration of 38 minutes consisting of a 10 minutes warm up on 30% of watt-max followed by 6 intervals of 1 minute at 100% of the watt-max. Each interval is interspersed by 3-minute active pauses at 30% of watt-max. Following this a 7-minute cooldown (at warm up intensity) will be performed. | Behavioral: Exercise training<br>* Feasibility and safety of 3 different training protocols will be tested. Therefore the intervention is three different exercise protocols (4X4, 6X1, and 10-20-30). The exercise workload is set according to the patients HRmax or wattmax from a VO2max test at the baseline testing. All training protocols have a duration of 38 minutes and start with a 10-minute warm up and a 3-7-minute cool-down period. The intervals in the training protocols are interspersed with a 3-minute active rest. Therefore the three exercise protocols are matched on duration, and they all fall within the category of high-intensity-interval training. The accumulated time spend with a heart rate >85% of HR max will be evaluated to determine the intensity.<br>|
| Active Comparator: 10-20-30<br>An exercise training protocol with a duration of 38 minutes consisting of a 10 minutes warm up at 60-70% of HRmax followed by 3 intervals of 5 minutes interspersed by 3 minutes on 50-70% of HRmax. Each interval consists of 5 minutes of 5 repeated 30-20-10 intervals, consisting of 30 seconds at easy pace, 20 seconds at medium pace and 10 seconds at all-out. Following this a 7-minute cooldown (at warm up intensity) will be performed. | Behavioral: Exercise training<br>* Feasibility and safety of 3 different training protocols will be tested. Therefore the intervention is three different exercise protocols (4X4, 6X1, and 10-20-30). The exercise workload is set according to the patients HRmax or wattmax from a VO2max test at the baseline testing. All training protocols have a duration of 38 minutes and start with a 10-minute warm up and a 3-7-minute cool-down period. The intervals in the training protocols are interspersed with a 3-minute active rest. Therefore the three exercise protocols are matched on duration, and they all fall within the category of high-intensity-interval training. The accumulated time spend with a heart rate >85% of HR max will be evaluated to determine the intensity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 10-point Likert scale | the 10-point Likert scale, which evaluates enjoyment and perceived tolerance of each training protocol at the end of each training session using a 10-point Likert scale, which is one of the most fundamental and frequently used psychometric tools in social science research. Patients have to indicate the degree to which they agreed with the following statement before training: How motivated are you for today's training? following two statements after the training: How enjoyable have today´s training session been? and How tolerant has today´s training been? A higher number describes better agreement. | Through study completion, an average of 3 months | 
| Participant adherence to the training dose | Percentage completed exercise of the total duration | Through study completion, an average of 3 months | 
| Participant adherence to the training intensity | Percentage of the exercise session spent at a heart rate above 85% of maximal heart rate | Through study completion, an average of 3 months | 
| Adverse effects | Adverse effect which leads to termination of the exercise training, registered as a binary outcome (yes/no) | Through study completion, an average of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of perceived exertion | Verification of training intensity is evaluated by rate of perceived exertion after each interval (6-20 Borg scale) and after completed training (1-10 Borg scale), and from accumulated minutes in the predefined heart rate zones. | The secondary outcome measure will be evaluated through study completion, an average of 3 months | 
| Post COVID-19 Functional scale | Functional capacity of the patients is another outcome which is assessed with the Post COVID-19 Functional scale, which is a scale to measure the consequence of the disease beyond binary outcomes. The scale ranges from 0-4, where 4 describes worst functional limitation (worse outcome). | The secondary outcome measure will be evaluated through study completion, an average of 3 months |