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

Stroke Clinical Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02680496
• Other study ID #: LOKOMAT STUDY I
• Secondary ID: SBO-IWT MIRAD pr
• Status: Terminated
• Phase: N/A
• First received: January 27, 2016
• Last updated: November 30, 2017
• Start date: February 2016
• Est. completion date: August 2017

Study information

• Verified date: November 2017
• Source: Vrije Universiteit Brussel
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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%.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: August 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Stroke

Intervention

Device:
• Lokomat
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)

Other:
• Treadmill
A single walking trial in which the patient walks on a treadmill for 30 minutes at comfortable walking speed (body-weight supported if necessary)
• Overground
A single walking trial in which the patient walks overground for 30 minutes at comfortable walking speed (body-weight supported if necessary)

Locations

Country	Name	City	State
Belgium	St. Ursula Rehabilitation Centre (Jessa Hospital)	Herk-de-Stad	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Vrije Universiteit Brussel

Country where clinical trial is conducted

Belgium, 

References & Publications (23)

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David D, Regnaux JP, Lejaille M, Louis A, Bussel B, Lofaso F. Oxygen consumption during machine-assisted and unassisted walking: a pilot study in hemiplegic and healthy humans. Arch Phys Med Rehabil. 2006 Apr;87(4):482-9. — View Citation

Delussu AS, Morone G, Iosa M, Bragoni M, Traballesi M, Paolucci S. Physiological responses and energy cost of walking on the Gait Trainer with and without body weight support in subacute stroke patients. J Neuroeng Rehabil. 2014 Apr 10;11:54. doi: 10.1186/1743-0003-11-54. — View Citation

Farris RJ, Quintero HA, Murray SA, Ha KH, Hartigan C, Goldfarb M. A preliminary assessment of legged mobility provided by a lower limb exoskeleton for persons with paraplegia. IEEE Trans Neural Syst Rehabil Eng. 2014 May;22(3):482-90. doi: 10.1109/TNSRE.2013.2268320. Epub 2013 Jun 18. — View Citation

Fenuta AM, Hicks AL. Metabolic demand and muscle activation during different forms of bodyweight supported locomotion in men with incomplete SCI. Biomed Res Int. 2014;2014:632765. doi: 10.1155/2014/632765. Epub 2014 May 21. — View Citation

Fletcher GF, Ades PA, Kligfield P, Arena R, Balady GJ, Bittner VA, Coke LA, Fleg JL, Forman DE, Gerber TC, Gulati M, Madan K, Rhodes J, Thompson PD, Williams MA; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee of the Council on Clinical Cardiology, Council on Nutrition, Physical Activity and Metabolism, Council on Cardiovascular and Stroke Nursing, and Council on Epidemiology and Prevention. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation. 2013 Aug 20;128(8):873-934. doi: 10.1161/CIR.0b013e31829b5b44. Epub 2013 Jul 22. — View Citation

Hornby TG, Kinnaird CR, Holleran CL, Rafferty MR, Rodriguez KS, Cain JB. Kinematic, muscular, and metabolic responses during exoskeletal-, elliptical-, or therapist-assisted stepping in people with incomplete spinal cord injury. Phys Ther. 2012 Oct;92(10):1278-91. doi: 10.2522/ptj.20110310. Epub 2012 Jun 14. — View Citation

Israel JF, Campbell DD, Kahn JH, Hornby TG. Metabolic costs and muscle activity patterns during robotic- and therapist-assisted treadmill walking in individuals with incomplete spinal cord injury. Phys Ther. 2006 Nov;86(11):1466-78. — View Citation

Kelly JO, Kilbreath SL, Davis GM, Zeman B, Raymond J. Cardiorespiratory fitness and walking ability in subacute stroke patients. Arch Phys Med Rehabil. 2003 Dec;84(12):1780-5. — View Citation

Kitatani R, Ohata K, Takahashi H, Shibuta S, Hashiguchi Y, Yamakami N. Reduction in energy expenditure during walking using an automated stride assistance device in healthy young adults. Arch Phys Med Rehabil. 2014 Nov;95(11):2128-33. doi: 10.1016/j.apmr.2014.07.008. Epub 2014 Jul 24. — View Citation

Krewer C, Müller F, Husemann B, Heller S, Quintern J, Koenig E. The influence of different Lokomat walking conditions on the energy expenditure of hemiparetic patients and healthy subjects. Gait Posture. 2007 Sep;26(3):372-7. Epub 2006 Nov 20. — View Citation

Maeshima S, Osawa A, Nishio D, Hirano Y, Takeda K, Kigawa H, Sankai Y. Efficacy of a hybrid assistive limb in post-stroke hemiplegic patients: a preliminary report. BMC Neurol. 2011 Sep 27;11:116. doi: 10.1186/1471-2377-11-116. — View Citation

Malcolm P, Derave W, Galle S, De Clercq D. A simple exoskeleton that assists plantarflexion can reduce the metabolic cost of human walking. PLoS One. 2013;8(2):e56137. doi: 10.1371/journal.pone.0056137. Epub 2013 Feb 13. — View Citation

Mehrholz J, Elsner B, Werner C, Kugler J, Pohl M. Electromechanical-assisted training for walking after stroke. Cochrane Database Syst Rev. 2013 Jul 25;(7):CD006185. doi: 10.1002/14651858.CD006185.pub3. Review. Update in: Cochrane Database Syst Rev. 2017 May 10;5:CD006185. — View Citation

Mehrholz J, Pohl M, Elsner B. Treadmill training and body weight support for walking after stroke. Cochrane Database Syst Rev. 2014 Jan 23;(1):CD002840. doi: 10.1002/14651858.CD002840.pub3. Review. Update in: Cochrane Database Syst Rev. 2017 Aug 17;8:CD002840. — View Citation

Myers J, McAuley P, Lavie CJ, Despres JP, Arena R, Kokkinos P. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status. Prog Cardiovasc Dis. 2015 Jan-Feb;57(4):306-14. doi: 10.1016/j.pcad.2014.09.011. Epub 2014 Sep 28. Review. — View Citation

Patterson KK, Gage WH, Brooks D, Black SE, McIlroy WE. Evaluation of gait symmetry after stroke: a comparison of current methods and recommendations for standardization. Gait Posture. 2010 Feb;31(2):241-6. doi: 10.1016/j.gaitpost.2009.10.014. Epub 2009 Nov 22. — View Citation

Smith AC, Saunders DH, Mead G. Cardiorespiratory fitness after stroke: a systematic review. Int J Stroke. 2012 Aug;7(6):499-510. doi: 10.1111/j.1747-4949.2012.00791.x. Epub 2012 May 9. Review. — View Citation

States RA, Salem Y, Pappas E. Overground gait training for individuals with chronic stroke: a Cochrane systematic review. J Neurol Phys Ther. 2009 Dec;33(4):179-86. doi: 10.1097/NPT.0b013e3181c29a8c. Review. — View Citation

Swinnen E, Beckwée D, Pinte D, Meeusen R, Baeyens JP, Kerckhofs E. Treadmill training in multiple sclerosis: can body weight support or robot assistance provide added value? A systematic review. Mult Scler Int. 2012;2012:240274. doi: 10.1155/2012/240274. Epub 2012 May 30. — View Citation

Swinnen E, Duerinck S, Baeyens JP, Meeusen R, Kerckhofs E. Effectiveness of robot-assisted gait training in persons with spinal cord injury: a systematic review. J Rehabil Med. 2010 Jun;42(6):520-6. doi: 10.2340/16501977-0538. Review. — View Citation

van Nunen MP, Gerrits KH, de Haan A, Janssen TW. Exercise intensity of robot-assisted walking versus overground walking in nonambulatory stroke patients. J Rehabil Res Dev. 2012;49(10):1537-46. — View Citation

Waters RL, Mulroy S. The energy expenditure of normal and pathologic gait. Gait Posture. 1999 Jul;9(3):207-31. Review. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Paretic cadence	The average amount of steps per minute at the paretic side at different time frames. Cadence will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic cadence	The average amount of steps per minute at the paretic side at different time frames. Cadence will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Cadence symmetry ratio	The ratio of paretic and non-paretic cadence with the numerator always being the greater of the two values, so that results are not skewed by values <1.0 (1.0 indicating perfect symmetry). Direction of asymmetry will be retained with a sign convention (e.g. +/- to indicate favoring of the paretic/non-paretic limb, respectively).	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic cadence variability	The average intra-subject variation in paretic cadence between consecutive gait cycles. Cadence will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic cadence variability	The average intra-subject variation in non-paretic cadence between consecutive gait cycles. Cadence will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic gait cycle time	The average duration of a gait cycle (expressed in seconds) at the paretic side at different time frames. Gait cycle time will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic gait cycle time	The average duration of a gait cycle (expressed in seconds) at the non-paretic side at different time frames. Gait cycle time will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Gait cycle time asymmetry ratio	The ratio of paretic and non-paretic gait cycle time with the numerator always being the greater of the two values, so that results are not skewed by values <1.0 (1.0 indicating perfect symmetry). Direction of asymmetry will be retained with a sign convention (e.g. +/- to indicate favoring of the paretic/non-paretic limb, respectively).	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic gait cycle time variability	The average intra-subject variation in paretic gait cycle time between consecutive gait cycles. Gait cycle time will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic gait cycle time variability	The average intra-subject variation in non-paretic gait cycle time between consecutive gait cycles. Gait cycle time will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic stance	The average portion of the cycle during which part of the paretic foot touches the ground (expressed in % of cycle duration) at different time frames. Stance ratio will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic stance	The average portion of the cycle during which part of the non-paretic foot touches the ground (expressed in % of cycle duration) at different time frames. Stance ratio will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Stance symmetry ratio	The ratio of paretic and non-paretic stance with the numerator always being the greater of the two values, so that results are not skewed by values <1.0 (1.0 indicating perfect symmetry). Direction of asymmetry will be retained with a sign convention (e.g. +/- to indicate favoring of the paretic/non-paretic limb, respectively).	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic stance variability	The average intra-subject variation in paretic stance between consecutive gait cycles. Stance will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic stance variability	The average intra-subject variation in non-paretic stance between consecutive gait cycles. Stance will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic swing	The average portion of the gait cycle during which the paretic foot is in the air and does not touch the ground (expressed in % of gait cycle) at different time frames. Swing ratio will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic swing	The average portion of the gait cycle during which the non-paretic foot is in the air and does not touch the ground (expressed in % of gait cycle) at different time frames. Swing ratio will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Swing symmetry ratio	The ratio of paretic and non-paretic swing with the numerator always being the greater of the two values, so that results are not skewed by values <1.0 (1.0 indicating perfect symmetry). Direction of asymmetry will be retained with a sign convention (e.g. +/- to indicate favoring of the paretic/non-paretic limb, respectively).	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic swing variability	The average intra-subject variation in paretic swing between consecutive gait cycles. Swing will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic swing variability	The average intra-subject variation in non-paretic swing between consecutive gait cycles. Swing will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Double support	The average portion of the cycle during which both feet touch the ground (expressed in % of cycle duration) at different time frames. Double support will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Double support variability	The average intra-subject variation in double support between consecutive gait cycles. Double support will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic stride length	The average distance (expressed in meters) between two successive paretic footprints on the ground, from the heel of the paretic foot to the heel of the paretic foot, one cycle after, at different time frames. Stride length will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic stride length	The average distance (expressed in meters) between two successive non-paretic footprints on the ground, from the heel of the non-paretic foot to the heel of the non-paretic foot, one cycle after, at different time frames. Stride length will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Stride length symmetry ratio	The ratio of paretic and non-paretic stride length with the numerator always being the greater of the two values, so that results are not skewed by values <1.0 (1.0 indicating perfect symmetry). Direction of asymmetry will be retained with a sign convention (e.g. +/- to indicate favoring of the paretic/non-paretic limb, respectively).	Minute 6, 18 and 30 of 30-minute walking period
Other	Paretic stride length variability	The average intra-subject variation in paretic stride length between consecutive gait cycles. Stride length will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Other	Non-paretic stride length variability	The average intra-subject variation in non-paretic stride length between consecutive gait cycles. Stride length will be measured continuously (from the beginning till the end of walking). Offline calculations will be performed afterwards.	Minute 6, 18 and 30 of 30-minute walking period
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)