Short Arm Human Centrifuge Therapeutic Training and Rehabilitation (GRACER1)

Stroke Clinical Trial

— GRACER1  

Official title:

Estimating the Optimal G Level for Training and Rehabilitation on a Short Arm Human Centrifuge

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04369976
• Other study ID #: 001955
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 1, 2020
• Est. completion date: December 1, 2024

Study information

• Verified date: February 2024
• Source: Greek Aerospace Medical Association and Space Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a single blind randomized controlled trial (RCT) designed to examine the benefit of a short arm human centrifuge intervention program (SAHC) combined with exercise, compared to a standard of care (SOC) rehabilitation program in physically impaired patients with MS, stroke, severe chronic obstructive pulmonary disease (COPD) and elderly people with balance and gait disorders (risk of falls).

Description:

The patients will be randomly assigned to the short arm human centrifuge training (SAHC intervention), standard of care (SOC training) or a passive control. The SAHC intervention consists of 3 sessions per week. The session duration is 1 hour. The intervention will last 3 months.

Aiming to estimate the minimum number of participants required for obtaining reliable results, the investigators performed power analysis. It was conducted in g-power 3.1 to determine a sufficient sample size using an alpha of 0.05, a power of 0.80, and a medium effect size (f = 0.21). Based on the aforementioned assumptions, a total sample size of 26 participants per group was computed.

The passive control group will abstain from any exercise. Initially, there will be one session serving as an evaluation and familiarization of the SAHC group participants on the centrifuge. Its aim besides familiarization will be also to individually assess the optimal according to the participant's cardiovascular functioning with cardiac output (CO), stroke volume (SV) mean arterial pressure (MAP) diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR). These criteria are monitored at each training session and are used to dynamically adapt the intervention intensity. More specifically, after 6 training sessions (2 weeks), the centrifugation load will be increased and considering the cardiovascular criteria, centrifugation will be combined with either aerobic exercise (through an ergometer) or resistance training through elastic training bands. Further verification of the dynamic configuration of the intervention will be provided by the electroencephalographic (EEG) assessment. More specifically, resting state EEG (eyes open & closed condition, lying in horizontal position) and centrifugation in three different intensities, mild (corresponding to 0.5,0.7, and 1 g), medium (corresponding to 1.2 and 1.5 g) and high intensity (corresponding to 1.7 and 2 g). Functional connectivity and cortical-network features derived from graph theory will be used by deep learning algorithms (convolutional neural networks) in order to define the optimal centrifuge training.

A set of core outcomes as described below will be collected at the following experimental time instances: a) baseline, b) after 4 weeks, c) 8 weeks, d) 3 months, e) 6-month follow-up, g) 12-month follow-up. The outcomes will be collected across the domains of body structure and function, activity, and participation as classified by the world health organization international classification of functioning (ICF), disability and health.

The primary outcomes are the following:

1. A set of cardiovascular biosignal sensors described above,

2. Electroencephalographic (EEG) recordings,

3. The functional gait assessment (FGA) and

4. The functioning differences assessed by changes in summary ordinal score on the short physical performance battery (SPPB). The battery consists of three tests: balance, gait ability and leg strength. The score for each test is given in categorical modality (0-4) based on run time intervals, and the total score will range from 0 (worst) to 12 points (best). The SPPB has been shown to be a valid instrument for screening frailty and predicting disability, institutionalization and mortality. A total score of less than 10 points indicates frailty and a high risk of disability and falls. 1 point change in the total score has demonstrated to be of clinical relevance.

More primary outcomes include other measures of gaze and postural stability, fatigue, and functional mobility, isokinetic strength and muscle oxygen consumption. Additionally, a set of biomarkers in blood and urine will be collected.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: December 1, 2024
• Est. primary completion date: March 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 17 Years to 90 Years

Eligibility

Inclusion Criteria:

• both male and female

• height less than 2 m,

• healthy or

• with gait disorder or

• impaired mobility from multiple sclerosis or

• stroke,

• chronic obstructive pulmonary disease (COPD) or

• elderly

Exclusion Criteria:

• Neurological or psychiatric disorder,

• vertigo,

• nausea or

• chronic pain,

• participants with a height greater than 2 meters,

• participants with chronic use of substances or alcoholism,

• with recent (within 6 months) surgery,

• current arrhythmia,

• severe migraines,

• pregnancy,

• epilepsy,

• cholelithiasis or

• kidney stones,

• dehydration,

• recent wounds from surgery,

• recent fractures (unless recommended by a doctor),

• acute inflammation or

• pain and

• newly inserted metal pins or plates, newly implanted stents .

Related Conditions & MeSH terms

• Aged
• Multiple Sclerosis
• Pulmonary Disease, Chronic Obstructive
• Stroke

Intervention

Device:
• ARTIFICIAL GRAVITY COMBINED WITH EXERCISE
The passive control group will abstain from any exercise. Recordings of the participant's will include cardiovascular functioning cardiac output (CO), stroke volume (SV) mean arterial pressure (MAP) diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR), Electroencephalography ( EEG) as well as dynamic force and stance and muscle oxygenation. More specifically, after 6 training sessions (2 weeks), the centrifugation load will be increased and will be combined with either aerobic exercise (through an ergometer) or resistance training through elastic training bands. Functional connectivity and cortical-network features will be used by deep learning algorithms in order to define the optimal centrifuge training .

Locations

Country	Name	City	State
Greece	Euromedica-Arogi Rehabilitation Center	Thessaloniki	FW

Sponsors (1)

Lead Sponsor	Collaborator
Greek Aerospace Medical Association and Space Research

Country where clinical trial is conducted

Greece, 

References & Publications (23)

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Diaz-Artiles A, Heldt T, Young LR. Short-Term Cardiovascular Response to Short-Radius Centrifugation With and Without Ergometer Exercise. Front Physiol. 2018 Nov 13;9:1492. doi: 10.3389/fphys.2018.01492. eCollection 2018. — View Citation

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Frett, T., Mayrhofer, M., Schwandtner, J. et al. An Innovative Short Arm Centrifuge for Future Studies on the Effects of Artificial Gravity on the Human Body. Microgravity Sci. Technol. 26, 249-255 (2014). https://doi.org/10.1007/s12217-014-9386-9 Received: 6 December 2013 / Accepted: 29 August 2014 / Published online: 19 September 2014 © Springer Science+Business Media Dordrecht 2014

Habazettl H, Stahn A, Nitsche A, Nordine M, Pries AR, Gunga HC, Opatz O. Microvascular responses to (hyper-)gravitational stress by short-arm human centrifuge: arteriolar vasoconstriction and venous pooling. Eur J Appl Physiol. 2016 Jan;116(1):57-65. doi: — View Citation

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Manen O, Dussault C, Sauvet F, Montmerle-Borgdorff S. Limitations of stroke volume estimation by non-invasive blood pressure monitoring in hypergravity. PLoS One. 2015 Mar 23;10(3):e0121936. doi: 10.1371/journal.pone.0121936. eCollection 2015. — View Citation

Martina JR, Westerhof BE, van Goudoever J, de Beaumont EM, Truijen J, Kim YS, Immink RV, Jobsis DA, Hollmann MW, Lahpor JR, de Mol BA, van Lieshout JJ. Noninvasive continuous arterial blood pressure monitoring with Nexfin(R). Anesthesiology. 2012 May;116(5):1092-103. doi: 10.1097/ALN.0b013e31824f94ed. — View Citation

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Trigg C. (2013). Design and Validation of a Compact Radius Centrifuge Artificial Gravity Test Platform. Ph.D. thesis, Massachusetts Institute of Technology, Cambridge.

Truijen J, van Lieshout JJ, Wesselink WA, Westerhof BE. Noninvasive continuous hemodynamic monitoring. J Clin Monit Comput. 2012 Aug;26(4):267-78. doi: 10.1007/s10877-012-9375-8. Epub 2012 Jun 14. — View Citation

van der Spoel AG, Voogel AJ, Folkers A, Boer C, Bouwman RA. Comparison of noninvasive continuous arterial waveform analysis (Nexfin) with transthoracic Doppler echocardiography for monitoring of cardiac output. J Clin Anesth. 2012 Jun;24(4):304-9. doi: 10 — View Citation

Verma AK, Xu D, Bruner M, Garg A, Goswami N, Blaber AP, Tavakolian K. Comparison of Autonomic Control of Blood Pressure During Standing and Artificial Gravity Induced via Short-Arm Human Centrifuge. Front Physiol. 2018 Jun 25;9:712. doi: 10.3389/fphys.201 — View Citation

Vernikos J. Artificial gravity intermittent centrifugation as a space flight countermeasure. J Gravit Physiol. 1997 Jul;4(2):P13-6. — View Citation

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Wang YC, Yang CB, Wu YH, Gao Y, Lu DY, Shi F, Wei XM, Sun XQ. Artificial gravity with ergometric exercise as a countermeasure against cardiovascular deconditioning during 4 days of head-down bed rest in humans. Eur J Appl Physiol. 2011 Sep;111(9):2315-25. — View Citation

Yang CB, Zhang S, Zhang Y, Wang B, Yao YJ, Wang YC, Wu YH, Liang WB, Sun XQ. Combined short-arm centrifuge and aerobic exercise training improves cardiovascular function and physical working capacity in humans. Med Sci Monit. 2010 Dec;16(12):CR575-83. — View Citation

Yang Y, Baker M, Graf S, Larson J, Caiozzo VJ. Hypergravity resistance exercise: the use of artificial gravity as potential countermeasure to microgravity. J Appl Physiol (1985). 2007 Nov;103(5):1879-87. doi: 10.1152/japplphysiol.00772.2007. Epub 2007 Sep 13. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiovascular physiological parameter 1 cardiac output (CO) 1-standing	Cardiac output (CO) unit L/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes standing condition	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 1 cardiac output (CO) 2-lying	Cardiac output (CO) unit L/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes lying condition	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 1 cardiac output (CO) 3-mild intensity	Cardiac output (CO) unit L/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes mild intensity centrifugation condition	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 1 cardiac output (CO) 4-medium intensity	Cardiac output (CO) unit L/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes medium intensity centrifugation condition	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 1 cardiac output (CO) 5-high intensity	Cardiac output (CO) unit L/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes high intensity centrifugation condition	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 2, Stroke volume (SV) 1-standing	Stroke volume (SV) unit L/beat, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes standing position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 2, Stroke volume (SV) 2-lying	Stroke volume (SV) unit L/beat, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes lying position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 2, Stroke volume (SV) 3-mild intensity	Stroke volume (SV) unit L/beat, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation of mild intensity (from 0,5 g to 1 g	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 2, Stroke volume (SV) 4-medium intensity	Stroke volume (SV) unit L/beat, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation of medium intensity (from 1,2g to1,5 g	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 2, Stroke volume (SV) 5-high intensity	Stroke volume (SV) unit L/beat, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation of high intensity (from 1,7g to 2 g)	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 1-standing	Mean arterial pressure (MAP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger at standing position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 2-lying	Mean arterial pressure (MAP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger at lying position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 3-mild intensity	Mean arterial pressure (MAP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after centrifugation with mild intensity (from 0,5 g to 1 g)	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 4-medium intensity	Mean arterial pressure (MAP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after centrifugation with medium intensity (from 1,2g to1,5 g)	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 5-high intensity	Mean arterial pressure (MAP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after centrifugation with high intensity (from 1,7g to 2 g).	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 1-standing	Diastolic blood pressure (DBP) unit mmHg,measured by a non invasive tensortip device attached to the subject's finger after 5 minutes standing position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 2-lying	Diastolic blood pressure (DBP) unit mmHg,measured by a non invasive tensortip device attached to the subject's finger after 5 minutes lying position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 3-low intensity	Diastolic blood pressure (DBP) unit mmHg,measured by a non invasive tensortip device attached to the subject's finger after centrifugation of mild intensity (from 0,5 g to 1 g).	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 4-medium intensity	Diastolic blood pressure (DBP) unit mmHg,measured by a non invasive tensortip device attached to the subject's finger after centrifugation with medium intensity (from 1,2g to1,5 g).	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 5-high intensity	Diastolic blood pressure (DBP) unit mmHg,measured by a non invasive tensortip device attached to the subject's finger after centrifugation of high intensity (from 1,7g to 2 g).	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 1-standing	Systolic blood pressure (SBP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes at standing position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 2;lying	Systolic blood pressure (SBP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes at lying position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 3-mild intensity	Systolic blood pressure (SBP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation with mild intensity (from 0,5 g to 1 g).	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 4-medium intensity	Systolic blood pressure (SBP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation with medium intensity (from 1,2g to1,5 g)	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 5-high intensity	Systolic blood pressure (SBP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation with high intensity (from 1,7g to 2 g)	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 6, heart rate (HR) 1-standing	Heart rate (HR) unit beats/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes at standing position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 6, heart rate (HR) 2-lying	Heart rate (HR) unit beats/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes at lying position	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 6, heart rate (HR) 3-mild intensity	Heart rate (HR) unit beats/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation of mild intensity (from 0,5 g to 1 g).	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 6, heart rate (HR) 4-medium intensity	Heart rate (HR) unit beats/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation with medium intensity (from 1,2g to1,5 g).	The time frame will include: changes from baseline up to 6 months
Primary	Cardiovascular physiological parameter 6, heart rate (HR) 5-high intensity	Heart rate (HR) unit beats/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes centrifugation of high intensity (from 1,7g to 2 g).	The time frame will include: changes from baseline up to 6 months
Primary	Electrical activity of the brain in alpha band, Electroencephalography (EEG)(µV) 1	Recording of the brain's spontaneous electrical activity using multiple electrodes placed on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Electrode locations and names are specified by the International 10-20 system.Each electrode is connected to one input of a differential amplifier, which amplifies the voltage between the active electrode and the reference (typically 1,000-100,000 times, or 60-100 dB of voltage gain) and the amplified signal is digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital sampling typically occurs at 256-512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz will be used .; The recording involves the subject with eyes open.	The time frame will include: changes from baseline up to 6 months
Primary	Electrical activity of the brain in alpha band, Electroencephalography (EEG)(µV) 2	Recording of the brain's spontaneous electrical activity using multiple electrodes placed on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Electrode locations and names are specified by the International 10-20 system.Each electrode is connected to one input of a differential amplifier, which amplifies the voltage between the active electrode and the reference (typically 1,000-100,000 times, or 60-100 dB of voltage gain) and the amplified signal is digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital sampling typically occurs at 256-512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz will be used .; The recording involves the subject with eyes closed.	The time frame will include: changes from baseline up to 6 months
Primary	Electrical activity of the brain in alpha band, Electroencephalography (EEG)(µV) 3	Recording of the brain's spontaneous electrical activity using multiple electrodes placed on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Electrode locations and names are specified by the International 10-20 system.Each electrode is connected to one input of a differential amplifier, which amplifies the voltage between the active electrode and the reference (typically 1,000-100,000 times, or 60-100 dB of voltage gain) and the amplified signal is digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital sampling typically occurs at 256-512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz will be used .; The recording involves the subject in standing position.	The time frame will include: changes from baseline up to 6 months
Primary	Electrical activity of the brain in alpha band, Electroencephalography (EEG)(µV) 4	Recording of the brain's spontaneous electrical activity using multiple electrodes placed on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Electrode locations and names are specified by the International 10-20 system.Each electrode is connected to one input of a differential amplifier, which amplifies the voltage between the active electrode and the reference (typically 1,000-100,000 times, or 60-100 dB of voltage gain) and the amplified signal is digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital sampling typically occurs at 256-512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz will be used .; The recording involves the subject in lying position.	The time frame will include: changes from baseline up to 6 months
Primary	Electrical activity of the brain in alpha band, Electroencephalography (EEG)(µV) 5	Recording of the brain's spontaneous electrical activity using multiple electrodes placed on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Electrode locations and names are specified by the International 10-20 system.Each electrode is connected to one input of a differential amplifier, which amplifies the voltage between the active electrode and the reference (typically 1,000-100,000 times, or 60-100 dB of voltage gain) and the amplified signal is digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital sampling typically occurs at 256-512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz will be used .; The recording involves the subject in centrifugation with mild intensity (from 0,5 g to 1 g).	The time frame will include: changes from baseline up to 6 months
Primary	Electrical activity of the brain in alpha band, Electroencephalography (EEG)(µV) 6	Recording of the brain's spontaneous electrical activity using multiple electrodes placed on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Electrode locations and names are specified by the International 10-20 system.Each electrode is connected to one input of a differential amplifier, which amplifies the voltage between the active electrode and the reference (typically 1,000-100,000 times, or 60-100 dB of voltage gain) and the amplified signal is digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital sampling typically occurs at 256-512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz will be used .; The recording involves the subject in centrifugation with medium intensity (from 1,2g to1,5 g).	The time frame will include: changes from baseline up to 6 months
Primary	Electrical activity of the brain in alpha band, Electroencephalography (EEG)(µV) 7	Recording of the brain's spontaneous electrical activity using multiple electrodes placed on the scalp with a conductive gel or paste, usually after preparing the scalp area by light abrasion to reduce impedance due to dead skin cells. Electrode locations and names are specified by the International 10-20 system.Each electrode is connected to one input of a differential amplifier, which amplifies the voltage between the active electrode and the reference (typically 1,000-100,000 times, or 60-100 dB of voltage gain) and the amplified signal is digitized via an analog-to-digital converter, after being passed through an anti-aliasing filter. Analog-to-digital sampling typically occurs at 256-512 Hz in clinical scalp EEG; sampling rates of up to 20 kHz will be used .; The recording involves the subject in centrifugation of high intensity (from 1,7g to 2 g).	The time frame will include: changes from baseline up to 6 months
Primary	The Short Physical Performance Battery assessment score	The functioning differences assessed by changes in summary ordinal score on Balance, gait ability and leg strength.; The score for each test is given in categorical modality (0-4) based on run time intervals, and the total score will range from 0 (worst) to 12 points (best).	The time frame will include: changes from baseline up to 6 months
Primary	The Functional Gait Assessment (FGA)	questionnaire	changes in 3 months
Primary	Gastrocnemius muscle oxygenation	Oxygen saturation (SmO2 (%)) of the gastrocnemius medialis muscle measured with muscle oxygen monitor" (MOXY) placed in the gastrocnemius muscle of the dominant leg during centrifugation	The time frame will include: changes in 3 months
Primary	Biological samples 1: CATECHOLAMINES	Unit of measurement: µmol from urine and saliva samples will be collected	The time frame will include: changes in 3 months
Primary	Biological samples 2: ADIPONECTINE	Unit of measurement: µg/mL from serum	The time frame will include: changes in 3 months
Primary	Biological samples 3:BDNF	Unit of measurement: ng/ml from serum	The time frame will include: changes in 3 months
Primary	Biological samples 4:MELATONINE	Unit of measurement: pg/mL from saliva	The time frame will include: changes in 3 months
Primary	Biological samples 5:ADENOSINE	Unit of measurement: µM from saliva	The time frame will include: changes in 3 months
Primary	Biological samples 5:TNF-a	Unit of measurement: pg/mL from serum	The time frame will include: changes in 3 months
Primary	Biological samples 6:IL-1ß	Unit of measurement: pg/mL from serum	The time frame will include: changes in 3 months
Primary	Biological samples 7:High-sensitivity C-reactive Protein (hs-CRP)	Unit of measurement: mg/L from serum	The time frame will include: changes in 3 months
Primary	Biological samples 8:Total leucocyte number:	Unit of measurement: number of cells x 10^3/µL from serum	The time frame will include: changes in 3 months
Primary	Biological samples 9:sTNF-RII	Unit of measurement: pg/ml from serum	The time frame will include: changes in 3 months
Primary	Biological samples 10:D-creatinine	Unit of measurement: mmol/l from serum	The time frame will include: changes in 3 months
Primary	Biological samples 11:alpha-amylase	Unit of measurement: IU, from serum	The time frame will include: changes in 3 months
Primary	Biological samples 12:secretory immunoglobulin A (sIgA)	Unit of measurement: mg/dL, from serum	The time frame will include: changes in 3 months
Primary	Biological samples 13: cortisol (SC) mg/dL	Unit of measurement: mg/dL, from saliva	The time frame will include: changes in 3 months
Primary	Biological samples 14: Glucose	Unit of measurement: mg/dL, from serum	The time frame will include: changes in 3 months
Primary	Biological samples 15: ACTH	Unit of measurement: ng/liter, from plasma	The time frame will include: changes in 3 months
Primary	Biological samples 16: Transcortin (mg/liter)	Unit of measurement: mg/liter, from serum	The time frame will include: changes in 3 months
Primary	Biological samples 17: Total antioxidant capacity (TAC)	Unit of measurement: mM Trolox equivalent/l , from saliva	The time frame will include: changes in 3 months
Primary	weight in kilograms, height in meters), as appropriate, or to clarify how multiple measurements will be aggregated to arrive at one reported value (e.g., weight	unit: Kg	changes in 3 months
Primary	Height	Unit:meters	Day 1only
Primary	Body Mass Index	Unit: kg/m^2).	changes in 3 months