Clinical trial NCT04369976: Short Arm Human Centrifuge Therapeutic Training and Rehabilitation (GRACER1)
Official title: Estimating the Optimal G Level for Training and Rehabilitation on a Short Arm Human Centrifuge
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Stroke
Pulmonary Disease, Chronic Obstructive
Aged
Lead sponsor: Greek Aerospace Medical Association and Space Research
Sponsor class: OTHER
First posted: 2020-04-30
Enrollment: 105
Sex: ALL
Minimum age (years): 17
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The use 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). The patients will be randomly assigned to the centrifuge training (SAHC intervention), SOC training or a passive control group. The SAHC intervention consists of 3 sessions per week. The session duration is 1 hour. The intervention will last for 3 months.
Primary purpose: PREVENTION

Brief 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).

Detailed 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.

Eligibility criteria: 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 .

Primary outcomes:
measure: Cardiovascular physiological parameter 1 cardiac output (CO) 1-standing
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 1 cardiac output (CO) 2-lying
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 1 cardiac output (CO) 3-mild intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 1 cardiac output (CO) 4-medium intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 1 cardiac output (CO) 5-high intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 2, Stroke volume (SV) 1-standing
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 2, Stroke volume (SV) 2-lying
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 2, Stroke volume (SV) 3-mild intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 2, Stroke volume (SV) 4-medium intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 2, Stroke volume (SV) 5-high intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 1-standing
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 2-lying
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 3-mild intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 4-medium intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 5-high intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 1-standing
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 2-lying
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 3-low intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 4-medium intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 5-high intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 1-standing
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 2;lying
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 3-mild intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 4-medium intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 5-high intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 6, heart rate (HR) 1-standing
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 6, heart rate (HR) 2-lying
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 6, heart rate (HR) 3-mild intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 6, heart rate (HR) 4-medium intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Cardiovascular physiological parameter 6, heart rate (HR) 5-high intensity
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 1
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 2
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 3
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 4
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 5
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 6
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 7
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: The Short Physical Performance Battery assessment score
timeFrame: The time frame will include: changes from baseline up to 6 months
measure: The Functional Gait Assessment (FGA)
timeFrame: changes in 3 months
measure: Gastrocnemius muscle oxygenation
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 1: CATECHOLAMINES
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 2: ADIPONECTINE
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 3:BDNF
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 4:MELATONINE
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 5:ADENOSINE
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 5:TNF-α
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 6:IL-1β
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 7:High-sensitivity C-reactive Protein (hs-CRP)
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 8:Total leucocyte number:
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 9:sTNF-RII
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 10:D-creatinine
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 11:alpha-amylase
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 12:secretory immunoglobulin A (sIgA)
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 13: cortisol (SC) mg/dL
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 14: Glucose
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 15: ACTH
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 16: Transcortin (mg/liter)
timeFrame: The time frame will include: changes in 3 months
measure: Biological samples 17: Total antioxidant capacity (TAC)
timeFrame: The time frame will include: changes in 3 months
measure: 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
timeFrame: changes in 3 months
measure: Height
timeFrame: Day 1only
measure: Body Mass Index
timeFrame: changes in 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: Euromedica-Arogi Rehabilitation Center
state: FW
Study officials:
affiliation: AeMC
name: CHRYSOULA KOURTIDOU-PAPADELI
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vernikos J. Human exploration of space: why, where, what for? Hippokratia. 2008 Aug;12 Suppl 1(Suppl 1):6-9.
citation: Hargens AR, Bhattacharya R, Schneider SM. Space physiology VI: exercise, artificial gravity, and countermeasure development for prolonged space flight. Eur J Appl Physiol. 2013 Sep;113(9):2183-92. doi: 10.1007/s00421-012-2523-5. Epub 2012 Oct 19.
citation: Vernikos J. Artificial gravity intermittent centrifugation as a space flight countermeasure. J Gravit Physiol. 1997 Jul;4(2):P13-6.
citation: 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
citation: Duda KR, Jarchow T, Young LR. Squat exercise biomechanics during short-radius centrifugation. Aviat Space Environ Med. 2012 Feb;83(2):102-10. doi: 10.3357/asem.2334.2012.
citation: Clement GR, Bukley AP, Paloski WH. Artificial gravity as a countermeasure for mitigating physiological deconditioning during long-duration space missions. Front Syst Neurosci. 2015 Jun 17;9:92. doi: 10.3389/fnsys.2015.00092. eCollection 2015.
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.
citation: Penaz J. (1973). "Photoelectric measurement of blood pressure, volume and flow in the finger," in Proceedings of the Digest 10th Int Conf Med Biol Engng, (Dresden: International Federation for Medical and Biological Engineering; ), 104.
citation: Stenger M. B., Evans J. M., Patwardhan A. R., Moore F. B., Hinghofer-Szalkay H., Rössler A., et al. (2007). Artificial gravity training improves orthostatic tolerance in ambulatory men and women. Acta Astronaut. 60 267-272. 10.3389/fphys.2018.00716
citation: Trigg C. (2013). Design and Validation of a Compact Radius Centrifuge Artificial Gravity Test Platform. Ph.D. thesis, Massachusetts Institute of Technology, Cambridge.
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.
citation: Chriskos P, Frantzidis CA, Gkivogkli PT, Bamidis PD, Kourtidou-Papadeli C. Automatic Sleep Staging Employing Convolutional Neural Networks and Cortical Connectivity Images. IEEE Trans Neural Netw Learn Syst. 2020 Jan;31(1):113-123. doi: 10.1109/TNNLS.2019.2899781. Epub 2019 Mar 15.
citation: LeBlanc A, Gogia P, Schneider V, Krebs J, Schonfeld E, Evans H. Calf muscle area and strength changes after five weeks of horizontal bed rest. Am J Sports Med. 1988 Nov-Dec;16(6):624-9. doi: 10.1177/036354658801600612.
citation: 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: 10.1007/s00421-015-3241-6. Epub 2015 Aug 18.
citation: Diaz Artiles, A., Heldt, T., and Young, L. R. (2016). Effects of artificial gravity on the cardio vascular system: computational approach. Acta Astronaut. 126, 395-410. doi: 10.1016/j.actaastro.2016.05.005.
citation: Katzmarzyk PT, Church TS, Craig CL, Bouchard C. Sitting time and mortality from all causes, cardiovascular disease, and cancer. Med Sci Sports Exerc. 2009 May;41(5):998-1005. doi: 10.1249/MSS.0b013e3181930355.
citation: 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.
citation: 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.
citation: 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.
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: 10.1016/j.jclinane.2011.09.008.
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.2018.00712. eCollection 2018.
citation: 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. doi: 10.1007/s00421-011-1866-7. Epub 2011 Feb 20.
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.