Biological and Functional Markers for Precision Astronautical Biomedicine

Study Overview
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Brief Summary
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In the current study the investigators will study early biomarkers of human degradation. In 10-day horizontal bed rest the investigators will enroll 10 healthy male subjects (18-30years, BMI 20-28kg/m2). Pre-, mid- and post-bed rest the investigators will perform various measurements, some of them will be invasive (blood samples and muscle biopsies), which will be carefully taken by the medical staff. The subjects will be placed in hospital rooms and have 24-hour medical supervision, adequate hygiene, nutrition, passive exercise, entertainment and visits.

Detailed Description
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Ten young male participants will undergo 10 days of horizontal bed rest. Before, during and after the investigators will monitor many biomechanical, metabolic, cardiovascular, biochemical responses. During the bed rest period there will be no interventions. subjects will be allowed to rotate freely, with no vertical stimulus of any-kind.

Official Title
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MARS-PRE: MARcatori Biologici e Funzionali Per la Biomedicina aStronautica di PREcisione

Conditions
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Muscular Atrophy

Intervention / Treatment
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* Other: Bed rest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index between 20 - 28 kg/m2 male participants a healthy individual who is able to complete all the tests planned in the research protocol Exclusion Criteria: smoking; regular alcohol consumption; ferromagnetic implants; history of deep vein thrombosis with D-dimer > 500 μg·L-1; acute or chronic skeletal, neuromuscular, psychological, metabolic and cardiovascular disease conditions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: One group of 10 will undergo 10 days of horizontal bed rest without countermeasures.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bed rest condition<br>Bed rest condition without any additional intervention | Other: Bed rest<br>* 10-day of complete bed rest<br>* Other names: prolonged physical inactivity;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mittochondria respiration rate | Change in Mittochondria oxygen respiration rate per mg of muscle tissue after 10-day bed rest | At baseline and after 10-day bed rest | 
| Change in skeletal muscle single fibre force (in micro Newtons) | In each aprticipants at each time point approx 10 intact muscle fibres will be studied for their force production after 10-day bed rest. Isometric muscle fibre force (in mNewton) will be measured isometric force (Fo) in four subsequent maximal activations (pCa, 4.6; sarcomere length, 2.6 micrometers; temperature 12 degrees C) using an electrical motor with force transducer mounted on it. | At baseline and after 10-day bed rest | 
| Change in Neurological outcomes - nerve conduction velocity | Change in nerve conduction velocity after 10-day bed rest | At baseline and after 10-day bed rest | 
| Change in Neurological outcomes - fMRI | Change in ability to mentally imagine/perform locomotory tasks (voxel-based network analyses) after 10-day bed rest | At baseline and after 10-day bed rest | 
| Change in Neurological outcomes - neurocognitive assessment | Change in EEG and neurocognitive tasks parameters (event related potential; P300 component during Stroop task) after 10-day bed rest | At baseline and after 10-day bed rest | 
| Change in skeletal muscle NCAM expression in single fibres | Neural cell adhesion molecule (NCAM) expression will be analysed in vastus lateralis biopsy samples at three time points. | Before, at day 5 and day 10 of bed rest | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle volume after 10-day bed rest | Thigh muscle volume will be assessed by continous section obtained by 3T MRI. Muscle segmentation will done by Matlab routine. | At baseline and after 10-day bed rest | 
| Change in peak aerobic power after 10-day bed rest | Change in peak aerobic power (maximal oxygen consumption) will be assessed on a cycloergometer using graded load protocol. | At baseline and after 10-day bed rest | 
| Nonhomogeneous change in skeletal muscle pennation angle after 10-day bed rest | Change in Muscle architecture will be assessed in vastus lateralis, biceps femoris, tibialis anterior, multifidus using sonography. Specifically, we will assess all three architecture parameters (pennation angle, fascicle length and thickness), however for the purspose of this outcome we hypothesize non-homogenous change throughout the whole muscles in pennation angle. The assessment will be performed before, every 2 days of bed rest and post bed rest. | At baseline, every 2 days of bed rest and after 10-day bed rest | 
| Change in maximal displacement after twitch contraction after 10-day bed rest | Using tensiomyography we will assess contraction time and maximal discplacement in vastus lateralis, tibialis anterior, biceps femoris, multifidus muscles. We expect that contraction time will remained the same but maximal diasplacement - a measure of a muscle tone, will increase much before the changes in muscle thickness - assessed by sonography. The assessment will be performed before, every 2 days of bed rest and post bed rest. | At baseline, every 2 days of bed rest and after 10-day bed rest | 
| Change in skeletal composition after 10-day bed rest | Using electrophoresis we will assess changes in myosing heavy chains somposition in the biopsies obtained from vastus lateralis muscle before, at day 5 and post 10 days of bed rest | At baseline, day 5 and after 10-day bed rest | 
| Change in skeletal muscle maximal voluntary contraction after 10-day bed rest | Maximal voluntary isometric knee extensors contraction will be measured using dnamometer set at 90 deg flexion. | At baseline and after 10-day bed rest | 
| Change in balance after 10-day bed rest | Change in static and dynamic balance will be assessed by functional tests (gait assessed with Optogait system and balance assessed with Tensiometric plate-COP) after 10-day bed rest | At baseline and after 10-day bed rest | 
| Change in orthostatic tolerance after 10-day bed rest | Change in mean arterial pressure during supine-to-stand test (mmHg) will be assessed by supine to stand test, where subjects will stay 10 minutes in each position. | At baseline and after 10-day bed rest |