Energy Consumption and Cardiorespiratory Load During Walking With and Without Robot-Assistance

Study Overview
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Brief Summary
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The primary objective of the study is to investigate the energy consumption, cardiorespiratory load and perceived exertion, and how these parameters change, during walking with robot-assistance compared to walking on a treadmill and walking overground in stroke patients. A secondary objective is to investigate whether these changes or differences in energy consumption, cardiorespiratory load and perceived exertion during walking with and without robot-assistance in stroke patients are related to changes or differences spatiotemporal gait characteristics.

Detailed Description
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Background. Impaired cardiorespiratory fitness, which is a major risk factor in the development of cardiorespiratory diseases, is frequently reported in stroke patients. The mean energy cost of walking, i.e. the amount of oxygen consumption in milliliter per kilogram of body-weight per meter, in stroke patients is almost twice as high compared to healthy subjects (resp. 0.27 ml/kg/m vs. 0.15 ml/kg/m). In the rehabilitation of stroke patients, the primary aim is to improve kinematic and functional gait-related parameters. However, due to the previously mentioned cardiorespiratory risks, it is important to be aware of the energy consumption and cardiorespiratory load of stroke patients during gait rehabilitation. In the past, gait training was mainly fulfilled by treadmill training, overground training and/or more conventional therapies, but in recent years, the implementation of robot-assistance in gait rehabilitation is increasing. However, what the influence is of robot-assistance on the cardiorespiratory load and energy consumption, and therefore also what potentially negative and/or positive side effects are for the cardiorespiratory system, is less investigated and unclear. Up to now, short walking durations of robot-assisted gait (up to 7 minutes) seem less energy consuming and cardiorespiratory stressful than walking without robot-assistance. However, what the influences are of longer walking durations is not clear. In addition, it is also unclear why possible differences between robot-assisted gait and walking without robot-assistance might exist. One possible explanation might be that differences in spatiotemporal gait parameters are responsible for differences in energy consumption and cardiorespiratory load. Patient recruitment. Stroke patients in the Rehabilitation Centre St. Ursula (Herk-de-Stad, Belgium) will receive verbal and written information on the aims and interventions of the study. Eligible stroke patients, who agree to participate in the study, will be recruited. Signed informed consent will be obtained from all participants. Sample size. Sample size calculation is based on previous investigations indicating large effect sizes between the effect of robot-assisted gait compared to walking without robot-assistance on energy consumption and cardiorespiratory load (based on a systematic review submitted for peer-review). To detect a large effect size (f = 0.40) of robot-assisted gait compared to overground and treadmill gait on energy consumption, cardiorespiratory load and perceived fatigue, in a repeated measures within subjects design (3 walking conditions and 4 measurements), with a significance level of 5% and a power level of 80%, a sample size of 21 subjects is needed (G*Power 3.1 for Mac). Sample size is inflated up to 24 subjects, so each walking order will be performed the same number of times. Intervention. Patients will be tested in 3 single walking sessions each on a separate day: walking in the Lokomat with 60% guidance force, walking on a treadmill and walking overground. Within subjects, all walking conditions will be performed at the same comfortable walking speed (CWS), with the same amount of body-weight support (BWS) (if necessary) during a total duration of maximum 30 minutes. The CWS (with a maximum of 3.2 kmph corresponding to the maximum Lokomat speed) and the amount of BWS (if necessary) will be individually determined on a separate day before the start of the study. Walking tests will be terminated early when relative or absolute indications are presented as reported by the American Heart Association or when patients are unable to continue walking. Patients will be asked to not consume food, alcohol, caffeine or nicotine at least 3 hours prior to the intervention, and not to perform additional strenuous activities at least 12 hours prior to the interventions. Walking sessions will be controlled for time of day. Before the start of the study, demographic and clinical characteristics will be collected and the CWS and the amount of BWS (if necessary) will be determined in a 10 minute walking test. At the start of each walking condition, a chest-carrying gas analysis system with mouth mask (Metamax 3B, Cortex, Germany), a heart rate belt (Polar H7) and 2 wearable foot sensors (Physiolog, Gait Up, Switzerland) will be applied. Patients will be seated for 5 minutes during which resting values (energy consumption, cardiorespiratory parameters and perceived fatigue) will be registered. After a resting period of 5 minutes, patients will walk for 30 minutes during which energy consumption, cardiorespiratory parameters, perceived fatigue and spatiotemporal parameters will be monitored continuously. Perceived fatigue will be registered every minute. Average values at rest, the beginning, middle and end of the walking sessions will be calculated offline. Randomization and Concealment. Walking sessions will be performed in a random order at 3 separate days. An independent investigator will assign the 24 patients (in 2 series of 12) at random to one of the 6 possible walking orders using a random sequence generator. Allocation will be concealed for the investigators using an excel file with blind and locked sections, to which only the independent investigator has access to. The random walking order of the patient will therefore only be available when the patient has been recruited and his name is entered in the excel sheet. This method will assure that the investigator does not know the walking order of the next participant. Dropout. In case subjects drop out, the subject will be replaced by a new participant who will perform all three trials in the same randomized order as the subject that dropped out. So, in case of drop out, additional patients will be tested until the data of 24 patients that participated in all three conditions are collected. Statistical analysis. Statistics will be performed using SPSS (IBM, Chicago, IL). Descriptive statistics will be calculated for baseline demographic and clinical patient characteristics. Repeated measures analyses of variance (ANOVA) with Bonferroni correction for multiple comparisons will be used to analyze differences in primary and secondary outcomes within and between walking conditions. Regression analysis will be performed to evaluate whether (changes in) spatiotemporal parameters are predictive for (changes in) energy consumption. The significance level will be set at 5%.

Conditions
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Stroke

Intervention / Treatment
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* Device: Lokomat
* Other: Treadmill
* Other: Overground


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stroke patients with a lower limb motor impairment Time since stroke < 1 year ≥ 18 years < 193 cm < 135kg Able to walk overground (body-weight support allowed if necessary) for at least 10 minutes at a comfortable walking speed Exclusion Criteria: Contra-indications for exercise testing according to the American College of Sports Medicine Musculoskeletal problems (other than stroke) affecting the ability to walk Concurrent pulmonary diseases Concurrent neurological diseases Communicative and/or cognitive problems affecting the ability to comprehend or follow instructions Other problems that affect the execution of the interventions, e.g. severe spasticity, contractures or dermatologic contraindications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lokomat - Treadmill - Overground<br>Walking order: lokomat walking, treadmill walking, overground walking | Device: Lokomat<br>* A single walking trial in which the patient walks in the Lokomat with 60% guidance force for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Treadmill<br>* A single walking trial in which the patient walks on a treadmill for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Overground<br>* A single walking trial in which the patient walks overground for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>|
| Experimental: Lokomat - Overground - Treadmill<br>Walking order: lokomat walking, overground walking, treadmill walking | Device: Lokomat<br>* A single walking trial in which the patient walks in the Lokomat with 60% guidance force for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Treadmill<br>* A single walking trial in which the patient walks on a treadmill for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Overground<br>* A single walking trial in which the patient walks overground for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>|
| Experimental: Treadmill - Lokomat - Overground<br>Walking order: treadmill walking, lokomat walking, overground walking | Device: Lokomat<br>* A single walking trial in which the patient walks in the Lokomat with 60% guidance force for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Treadmill<br>* A single walking trial in which the patient walks on a treadmill for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Overground<br>* A single walking trial in which the patient walks overground for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>|
| Experimental: Treadmill - Overground - Lokomat<br>Walking order: treadmill walking, overground walking, lokomat walking | Device: Lokomat<br>* A single walking trial in which the patient walks in the Lokomat with 60% guidance force for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Treadmill<br>* A single walking trial in which the patient walks on a treadmill for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Overground<br>* A single walking trial in which the patient walks overground for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>|
| Experimental: Overground - Lokomat - Treadmill<br>Walking order: overground walking, lokomat walking, treadmill walking | Device: Lokomat<br>* A single walking trial in which the patient walks in the Lokomat with 60% guidance force for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Treadmill<br>* A single walking trial in which the patient walks on a treadmill for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Overground<br>* A single walking trial in which the patient walks overground for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>|
| Experimental: Overground - Treadmill - Lokomat<br>Walking order: overground walking, treadmill walking, lokomat walking | Device: Lokomat<br>* A single walking trial in which the patient walks in the Lokomat with 60% guidance force for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Treadmill<br>* A single walking trial in which the patient walks on a treadmill for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>Other: Overground<br>* A single walking trial in which the patient walks overground for 30 minutes at comfortable walking speed (body-weight supported if necessary)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gross oxygen consumption (VO2) at rest | Average oxygen consumption (mL/kg/min). Oxygen consumption will be measured continuously (from the beginning of rest till the end of walking). Offline calculations (e.g. averages) will be performed afterwards. | Minute 5 of 5-minute resting period | 
| Gross oxygen consumption (VO2) at begin of walking | Average oxygen consumption (mL/kg/min). Oxygen consumption will be measured continuously (from the beginning of rest till the end of walking). Offline calculations (e.g. averages) will be performed afterwards. | Minute 6 of 30-minute walking period | 
| Gross oxygen consumption (VO2) at mid of walking | Average oxygen consumption (mL/kg/min). Oxygen consumption will be measured continuously (from the beginning of rest till the end of walking). Offline calculations (e.g. averages) will be performed afterwards. | Minute 18 of 30-minute walking period | 
| Gross oxygen consumption (VO2) at end of walking | Average oxygen consumption (mL/kg/min). Oxygen consumption will be measured continuously (from the beginning of rest till the end of walking). Offline calculations (e.g. averages) will be performed afterwards. | Minute 30 of 30-minute walking period | 
| Net oxygen consumption (VO2) | Change in average oxygen consumption (mL/kg/min) at different time frames during walking compared to rest. VO2 will be measured continuously (from the beginning of rest till the end of walking). Offline calculations will be performed afterwards. | Change between average VO2 at minute 5 of rest and minute 6 of walking, at minute 5 of rest and minute 18 of walking, at minute 5 of rest and minute 30 of walking | 
| Gross minute ventilation (VE) at rest | Average amount of air in- or exhaled (L/min). VE will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 5 of 5-minute resting period | 
| Gross minute ventilation (VE) at begin of walking | Average amount of air in- or exhaled (L/min). VE will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 6 of 30-minute walking period | 
| Gross minute ventilation (VE) at mid of walking | Average amount of air in- or exhaled (L/min). VE will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 18 of 30-minute walking period | 
| Gross minute ventilation (VE) at end of walking | Average amount of air in- or exhaled (L/min). VE will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 30 of 30-minute walking period | 
| Net minute ventilation (VE) | Change in average amount of air in- or exhaled (L/min) at different time frames during walking compared to rest. VE will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Change between average VE at minute 5 of rest and minute 6 of walking, at minute 5 of rest and minute 18 of walking, at minute 5 of rest and minute 30 of walking | 
| Gross respiration rate (RR) at rest | Average breaths per minute. Respiration rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 5 of 5-minute resting period | 
| Gross respiration rate (RR) at begin of walking | Average breaths per minute. Respiration rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 6 of 30-minute walking period | 
| Gross respiration rate (RR) at mid of walking | Average breaths per minute. Respiration rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 18 of 30-minute walking period | 
| Gross respiration rate (RR) at end of walking | Average breaths per minute. Respiration rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 30 of 30-minute walking period | 
| Net respiration rate (RR) | Change in respiration rate (breaths per minute) at different time frames during walking compared to rest. Respiration rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Change between average respiration rate at minute 5 of rest and minute 6 of walking, at minute 5 of rest and minute 18 of walking, at minute 5 of rest and minute 30 of walking | 
| Gross heart rate (HR) at rest | Average heart rate (beats/min). Heart rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 5 of 5-minute resting period | 
| Gross heart rate (HR) at begin of walking | Average heart rate (beats/min). Heart rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 6 of 30-minute walking period | 
| Gross heart rate (HR) at mid of walking | Average heart rate (beats/min). Heart rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 18 of 30-minute walking period | 
| Gross heart rate (HR) at end of walking | Average heart rate (beats/min). Heart rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Minute 30 of 30-minute walking period | 
| Net heart rate (HR) | Change in average heart rate (beats/min) at different time frames during walking compared to rest. Heart rate will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Change between average heart rate at minute 5 of rest and minute 6 of walking, at minute 5 of rest and minute 18 of walking, at minute 5 of rest and minute 30 of walking | 
| Gross Respiratory Exchange Ratio (RER) at rest | RER is the ratio between the amount of CO2 produced by the body and the amount of VO2 consumed by the body (VCO2/VO2). This ratio gives an indication of the type of fuel used to produce ATP. | Minute 5 of 5-minute resting period | 
| Gross Respiratory Exchange Ratio (RER) at begin of walking | RER is the ratio between the amount of CO2 produced by the body and the amount of VO2 consumed by the body (VCO2/VO2). This ratio gives an indication of the type of fuel used to produce ATP. | Minute 6 of 30-minute walking period | 
| Gross Respiratory Exchange Ratio (RER) at mid of walking | RER is the ratio between the amount of CO2 produced by the body and the amount of VO2 consumed by the body (VCO2/VO2). This ratio gives an indication of the type of fuel used to produce ATP. | Minute 18 of 30-minute walking period | 
| Gross Respiratory Exchange Ratio (RER) at end of walking | RER is the ratio between the amount of CO2 produced by the body and the amount of VO2 consumed by the body (VCO2/VO2). This ratio gives an indication of the type of fuel used to produce ATP. | Minute 30 of 30-minute walking period | 
| Net Respiratory Exchange Ratio (RER) | Change in RER at different time frames during walking compared to rest. RER will be measured continuously (from the beginning of rest till the end of the walking session). Offline calculations will be performed afterwards. | Change between average RER at minute 5 of rest and minute 6 of walking, at minute 5 of rest and minute 18 of walking, at minute 5 of rest and minute 30 of walking | 
| Metabolic Equivalent of Task (MET) at begin of walking | Expression of the intensity of physical activity (at different time frames) defined as oxygen consumption during walking divided by reference oxygen consumption in rest. Oxygen consumption will be measured continuously (from the beginning of rest till the end of walking). Offline calculations will be performed afterwards. | Minute 6 of 30-minute walking period | 
| Metabolic Equivalent of Task (MET) at mid of walking | Expression of the intensity of physical activity (at different time frames) defined as oxygen consumption during walking divided by reference oxygen consumption in rest. Oxygen consumption will be measured continuously (from the beginning of rest till the end of walking). Offline calculations will be performed afterwards. | Minute 18 of 30-minute walking period | 
| Metabolic Equivalent of Task (MET) at end of walking | Expression of the intensity of physical activity (at different time frames) defined as oxygen consumption during walking divided by reference oxygen consumption in rest. Oxygen consumption will be measured continuously (from the beginning of rest till the end of walking). Offline calculations will be performed afterwards | Minute 30 of 30-minute walking period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gross perceived exertion (assessed by the 6-20 Borg scale) at rest | Rating of perceived effort, strain and/or fatigue pointed on a 15-point Borg scale (6-20). Borg score will be measured at the end of rest (min 5) and at the end of every minute of walking. | Minute 5 of 5-minute resting period | 
| Gross perceived exertion (assessed by the 6-20 Borg scale) at begin of walking | Rating of perceived effort, strain and/or fatigue pointed on a 15-point Borg scale (6-20). Borg score will be measured at the end of rest (min 5) and at the end of every minute of walking. | Minute 6 of 30-minute walking period | 
| Gross perceived exertion (assessed by the 6-20 Borg scale) at mid of walking | Rating of perceived effort, strain and/or fatigue pointed on a 15-point Borg scale (6-20). Borg score will be measured at the end of rest (min 5) and at the end of every minute of walking. | Minute 18 of 30-minute walking period | 
| Gross perceived exertion (assessed by the 6-20 Borg scale) at end of walking | Rating of perceived effort, strain and/or fatigue pointed on a 15-point Borg scale (6-20). Borg score will be measured at the end of rest (min 5) and at the end of every minute of walking. | Minute 30 of 30-minute walking period | 
| Net perceived exertion (assessed by the 6-20 Borg scale) | Change in Borg score at different time frames during walking compared to rest. Borg score will be measured at the end of rest (min 5) and at the end of every minute of walking. | Change between Borg score at minute 5 of rest and minute 6 of walking, at minute 5 of rest and minute 18 of walking, at minute 5 of rest and minute 30 of walking | 
| Total walking duration | Total walking duration the patient can achieve in a single walking session (with a maximum of 30 minutes) | Begin till end of walking (up to 30 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Robot-Assistance, Gait [MeSH], Energy Consumption, Cardiorespiratory Load, Stroke [MeSH]