Aged, Multiple Sclerosis, Pulmonary Disease, Chronic Obstructive, Stroke
Conditions
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.
Interventions
DEVICEARTIFICIAL 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 .
Sponsors
Greek Aerospace Medical Association and Space Research
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
17 Years to 90 Years
Healthy volunteers
Yes
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 .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular physiological parameter 1 cardiac output (CO) 1-standing | The time frame will include: changes from baseline up to 6 months | Cardiac output (CO) unit L/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes standing condition |
| Cardiovascular physiological parameter 1 cardiac output (CO) 2-lying | The time frame will include: changes from baseline up to 6 months | Cardiac output (CO) unit L/min, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes lying condition |
| Cardiovascular physiological parameter 1 cardiac output (CO) 3-mild intensity | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 1 cardiac output (CO) 4-medium intensity | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 1 cardiac output (CO) 5-high intensity | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 2, Stroke volume (SV) 1-standing | The time frame will include: changes from baseline up to 6 months | Stroke volume (SV) unit L/beat, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes standing position |
| Cardiovascular physiological parameter 2, Stroke volume (SV) 2-lying | The time frame will include: changes from baseline up to 6 months | Stroke volume (SV) unit L/beat, measured by a non invasive tensortip device attached to the subject's finger after 5 minutes lying position |
| Cardiovascular physiological parameter 2, Stroke volume (SV) 3-mild intensity | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 2, Stroke volume (SV) 4-medium intensity | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 2, Stroke volume (SV) 5-high intensity | The time frame will include: changes from baseline up to 6 months | 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) |
| Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 1-standing | The time frame will include: changes from baseline up to 6 months | Mean arterial pressure (MAP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger at standing position |
| Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 2-lying | The time frame will include: changes from baseline up to 6 months | Mean arterial pressure (MAP) unit mmHg, measured by a non invasive tensortip device attached to the subject's finger at lying position |
| Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 3-mild intensity | The time frame will include: changes from baseline up to 6 months | 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) |
| Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 4-medium intensity | The time frame will include: changes from baseline up to 6 months | 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) |
| Cardiovascular physiological parameter 3, mean arterial pressure (MAP) 5-high intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 1-standing | The time frame will include: changes from baseline up to 6 months | Diastolic blood pressure (DBP) unit mmHg,measured by a non invasive tensortip device attached to the subject's finger after 5 minutes standing position |
| Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 2-lying | The time frame will include: changes from baseline up to 6 months | Diastolic blood pressure (DBP) unit mmHg,measured by a non invasive tensortip device attached to the subject's finger after 5 minutes lying position |
| Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 3-low intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 4-medium intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Cardiovascular physiological parameter 4, diastolic blood pressure (DBP) 5-high intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 1-standing | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 2;lying | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 3-mild intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 4-medium intensity | The time frame will include: changes from baseline up to 6 months | 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) |
| Cardiovascular physiological parameter 5, systolic blood pressure (SBP) 5-high intensity | The time frame will include: changes from baseline up to 6 months | 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) |
| Cardiovascular physiological parameter 6, heart rate (HR) 1-standing | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 6, heart rate (HR) 2-lying | The time frame will include: changes from baseline up to 6 months | 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 |
| Cardiovascular physiological parameter 6, heart rate (HR) 3-mild intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Cardiovascular physiological parameter 6, heart rate (HR) 4-medium intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Cardiovascular physiological parameter 6, heart rate (HR) 5-high intensity | The time frame will include: changes from baseline up to 6 months | 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). |
| Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 1 | The time frame will include: changes from baseline up to 6 months | 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. |
| Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 2 | The time frame will include: changes from baseline up to 6 months | 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. |
| Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 3 | The time frame will include: changes from baseline up to 6 months | 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. |
| Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 4 | The time frame will include: changes from baseline up to 6 months | 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. |
| Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 5 | The time frame will include: changes from baseline up to 6 months | 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). |
| Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 6 | The time frame will include: changes from baseline up to 6 months | 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). |
| Electrical activity of the brain in alpha band, Electroencephalography (EEG)(μV) 7 | The time frame will include: changes from baseline up to 6 months | 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 Short Physical Performance Battery assessment score | The time frame will include: changes from baseline up to 6 months | 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 Functional Gait Assessment (FGA) | changes in 3 months | questionnaire |
| Gastrocnemius muscle oxygenation | The time frame will include: changes in 3 months | 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 |
| Biological samples 1: CATECHOLAMINES | The time frame will include: changes in 3 months | Unit of measurement: μmol from urine and saliva samples will be collected |
| Biological samples 2: ADIPONECTINE | The time frame will include: changes in 3 months | Unit of measurement: μg/mL from serum |
| Biological samples 3:BDNF | The time frame will include: changes in 3 months | Unit of measurement: ng/ml from serum |
| Biological samples 4:MELATONINE | The time frame will include: changes in 3 months | Unit of measurement: pg/mL from saliva |
| Biological samples 5:ADENOSINE | The time frame will include: changes in 3 months | Unit of measurement: µM from saliva |
| Biological samples 5:TNF-α | The time frame will include: changes in 3 months | Unit of measurement: pg/mL from serum |
| Biological samples 6:IL-1β | The time frame will include: changes in 3 months | Unit of measurement: pg/mL from serum |
| Biological samples 7:High-sensitivity C-reactive Protein (hs-CRP) | The time frame will include: changes in 3 months | Unit of measurement: mg/L from serum |
| Biological samples 8:Total leucocyte number: | The time frame will include: changes in 3 months | Unit of measurement: number of cells x 10\^3/μL from serum |
| Biological samples 9:sTNF-RII | The time frame will include: changes in 3 months | Unit of measurement: pg/ml from serum |
| Biological samples 10:D-creatinine | The time frame will include: changes in 3 months | Unit of measurement: mmol/l from serum |
| Biological samples 11:alpha-amylase | The time frame will include: changes in 3 months | Unit of measurement: IU, from serum |
| Biological samples 12:secretory immunoglobulin A (sIgA) | The time frame will include: changes in 3 months | Unit of measurement: mg/dL, from serum |
| Biological samples 13: cortisol (SC) mg/dL | The time frame will include: changes in 3 months | Unit of measurement: mg/dL, from saliva |
| Biological samples 14: Glucose | The time frame will include: changes in 3 months | Unit of measurement: mg/dL, from serum |
| Biological samples 15: ACTH | The time frame will include: changes in 3 months | Unit of measurement: ng/liter, from plasma |
| Biological samples 16: Transcortin (mg/liter) | The time frame will include: changes in 3 months | Unit of measurement: mg/liter, from serum |
| Biological samples 17: Total antioxidant capacity (TAC) | The time frame will include: changes in 3 months | Unit of measurement: mM Trolox equivalent/l , from saliva |
| 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 | changes in 3 months | unit: Kg |
| Height | Day 1only | Unit:meters |
| Body Mass Index | changes in 3 months | Unit: kg/m\^2). |
Countries
Greece
Outcome results
None listed