Biological and Functional Markers for Precision Astronautical Biomedicine (MARS-PRE)
Primary Purpose
Muscular Atrophy
Status
Completed
Phase
Not Applicable
Locations
Slovenia
Study Type
Interventional
Intervention
Bed rest
Sponsored by
About this trial
This is an interventional treatment trial for Muscular Atrophy
Eligibility Criteria
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.
Sites / Locations
- Splosna bolnisnica Izola (Hospital of Izola)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
bed rest condition
Arm Description
Bed rest condition without any additional intervention
Outcomes
Primary Outcome Measures
Change in mittochondria respiration rate
Change in Mittochondria oxygen respiration rate per mg of muscle tissue 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.
Change in Neurological outcomes - nerve conduction velocity
Change in nerve conduction velocity 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
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
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.
Secondary Outcome Measures
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.
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.
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.
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.
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
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.
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
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.
Full Information
NCT ID
NCT04081467
First Posted
July 31, 2019
Last Updated
April 29, 2020
Sponsor
Science and Research Centre Koper
Collaborators
University of Padova, University of Bari, University of Genova, University of L'Aquila, University of Pavia, University of Trieste, Humanitas Hospital, Italy, University of Rome
1. Study Identification
Unique Protocol Identification Number
NCT04081467
Brief Title
Biological and Functional Markers for Precision Astronautical Biomedicine
Acronym
MARS-PRE
Official Title
MARS-PRE: MARcatori Biologici e Funzionali Per la Biomedicina aStronautica di PREcisione
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
August 28, 2019 (Actual)
Primary Completion Date
October 16, 2019 (Actual)
Study Completion Date
October 16, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Science and Research Centre Koper
Collaborators
University of Padova, University of Bari, University of Genova, University of L'Aquila, University of Pavia, University of Trieste, Humanitas Hospital, Italy, University of Rome
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Atrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
One group of 10 will undergo 10 days of horizontal bed rest without countermeasures.
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bed rest condition
Arm Type
Experimental
Arm Description
Bed rest condition without any additional intervention
Intervention Type
Other
Intervention Name(s)
Bed rest
Other Intervention Name(s)
immobilization, bed rest confinement, prolonged physical inactivity
Intervention Description
10-day of complete bed rest
Primary Outcome Measure Information:
Title
Change in mittochondria respiration rate
Description
Change in Mittochondria oxygen respiration rate per mg of muscle tissue after 10-day bed rest
Time Frame
At baseline and after 10-day bed rest
Title
Change in skeletal muscle single fibre force (in micro Newtons)
Description
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.
Time Frame
At baseline and after 10-day bed rest
Title
Change in Neurological outcomes - nerve conduction velocity
Description
Change in nerve conduction velocity after 10-day bed rest
Time Frame
At baseline and after 10-day bed rest
Title
Change in Neurological outcomes - fMRI
Description
Change in ability to mentally imagine/perform locomotory tasks (voxel-based network analyses) after 10-day bed rest
Time Frame
At baseline and after 10-day bed rest
Title
Change in Neurological outcomes - neurocognitive assessment
Description
Change in EEG and neurocognitive tasks parameters (event related potential; P300 component during Stroop task) after 10-day bed rest
Time Frame
At baseline and after 10-day bed rest
Title
Change in skeletal muscle NCAM expression in single fibres
Description
Neural cell adhesion molecule (NCAM) expression will be analysed in vastus lateralis biopsy samples at three time points.
Time Frame
Before, at day 5 and day 10 of bed rest
Secondary Outcome Measure Information:
Title
Change in muscle volume after 10-day bed rest
Description
Thigh muscle volume will be assessed by continous section obtained by 3T MRI. Muscle segmentation will done by Matlab routine.
Time Frame
At baseline and after 10-day bed rest
Title
Change in peak aerobic power after 10-day bed rest
Description
Change in peak aerobic power (maximal oxygen consumption) will be assessed on a cycloergometer using graded load protocol.
Time Frame
At baseline and after 10-day bed rest
Title
Nonhomogeneous change in skeletal muscle pennation angle after 10-day bed rest
Description
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.
Time Frame
At baseline, every 2 days of bed rest and after 10-day bed rest
Title
Change in maximal displacement after twitch contraction after 10-day bed rest
Description
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.
Time Frame
At baseline, every 2 days of bed rest and after 10-day bed rest
Title
Change in skeletal composition after 10-day bed rest
Description
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
Time Frame
At baseline, day 5 and after 10-day bed rest
Title
Change in skeletal muscle maximal voluntary contraction after 10-day bed rest
Description
Maximal voluntary isometric knee extensors contraction will be measured using dnamometer set at 90 deg flexion.
Time Frame
At baseline and after 10-day bed rest
Title
Change in balance after 10-day bed rest
Description
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
Time Frame
At baseline and after 10-day bed rest
Title
Change in orthostatic tolerance after 10-day bed rest
Description
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.
Time Frame
At baseline and after 10-day bed rest
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Facility Information:
Facility Name
Splosna bolnisnica Izola (Hospital of Izola)
City
Izola
ZIP/Postal Code
6310
Country
Slovenia
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
The data is shared among partners for various publications
Citations:
PubMed Identifier
26823343
Citation
Pisot R, Marusic U, Biolo G, Mazzucco S, Lazzer S, Grassi B, Reggiani C, Toniolo L, di Prampero PE, Passaro A, Narici M, Mohammed S, Rittweger J, Gasparini M, Gabrijelcic Blenkus M, Simunic B. Greater loss in muscle mass and function but smaller metabolic alterations in older compared with younger men following 2 wk of bed rest and recovery. J Appl Physiol (1985). 2016 Apr 15;120(8):922-9. doi: 10.1152/japplphysiol.00858.2015. Epub 2016 Jan 28.
Results Reference
background
PubMed Identifier
30676871
Citation
Simunic B, Koren K, Rittweger J, Lazzer S, Reggiani C, Rejc E, Pisot R, Narici M, Degens H. Tensiomyography detects early hallmarks of bed-rest-induced atrophy before changes in muscle architecture. J Appl Physiol (1985). 2019 Apr 1;126(4):815-822. doi: 10.1152/japplphysiol.00880.2018. Epub 2019 Jan 24.
Results Reference
background
PubMed Identifier
29529070
Citation
Floreani M, Rejc E, Taboga P, Ganzini A, Pisot R, Simunic B, Biolo G, Reggiani C, Passaro A, Narici M, Rittweger J, di Prampero PE, Lazzer S. Effects of 14 days of bed rest and following physical training on metabolic cost, mechanical work, and efficiency during walking in older and young healthy males. PLoS One. 2018 Mar 12;13(3):e0194291. doi: 10.1371/journal.pone.0194291. eCollection 2018.
Results Reference
background
PubMed Identifier
29266264
Citation
Rejc E, Floreani M, Taboga P, Botter A, Toniolo L, Cancellara L, Narici M, Simunic B, Pisot R, Biolo G, Passaro A, Rittweger J, Reggiani C, Lazzer S. Loss of maximal explosive power of lower limbs after 2 weeks of disuse and incomplete recovery after retraining in older adults. J Physiol. 2018 Feb 15;596(4):647-665. doi: 10.1113/JP274772. Epub 2018 Jan 19.
Results Reference
background
PubMed Identifier
28161695
Citation
Passaro A, Soavi C, Marusic U, Rejc E, Sanz JM, Morieri ML, Nora ED, Kavcic V, Narici MV, Reggiani C, Biolo G, Zuliani G, Lazzer S, Pisot R. Computerized cognitive training and brain derived neurotrophic factor during bed rest: mechanisms to protect individual during acute stress. Aging (Albany NY). 2017 Feb 3;9(2):393-407. doi: 10.18632/aging.101166.
Results Reference
background
PubMed Identifier
27937138
Citation
Marusic U, Giordani B, Moffat SD, Petric M, Dolenc P, Pisot R, Kavcic V. Computerized cognitive training during physical inactivity improves executive functioning in older adults. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2018 Jan;25(1):49-69. doi: 10.1080/13825585.2016.1263724. Epub 2016 Dec 12.
Results Reference
background
PubMed Identifier
25938245
Citation
Marusic U, Kavcic V, Giordani B, Gerzevic M, Meeusen R, Pisot R. Computerized spatial navigation training during 14 days of bed rest in healthy older adult men: Effect on gait performance. Psychol Aging. 2015 Jun;30(2):334-340. doi: 10.1037/pag0000021. Epub 2015 May 4.
Results Reference
background
PubMed Identifier
24734884
Citation
Marusic U, Meeusen R, Pisot R, Kavcic V. The brain in micro- and hypergravity: the effects of changing gravity on the brain electrocortical activity. Eur J Sport Sci. 2014;14(8):813-22. doi: 10.1080/17461391.2014.908959. Epub 2014 Apr 15.
Results Reference
background
PubMed Identifier
25613402
Citation
Rejc E, di Prampero PE, Lazzer S, Grassi B, Simunic B, Pisot R, Antonutto G, Narici M. A 35-day bed rest does not alter the bilateral deficit of the lower limbs during explosive efforts. Eur J Appl Physiol. 2015 Jun;115(6):1323-30. doi: 10.1007/s00421-015-3111-2. Epub 2015 Jan 23.
Results Reference
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Biological and Functional Markers for Precision Astronautical Biomedicine
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