Biological and Functional Markers for Precision Astronautical Biomedicine

Muscular Atrophy Clinical Trial

— MARS-PRE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04081467
• Other study ID #: BR2019 MARS-PRE
• Status: Completed
• Phase: N/A
• Start date: August 28, 2019
• Est. completion date: October 16, 2019

Study information

• Verified date: April 2020
• Source: Science and Research Centre Koper
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 16, 2019
• Est. primary completion date: October 16, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 30 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy

Intervention

Other:
• Bed rest
10-day of complete bed rest

Locations

Country	Name	City	State
Slovenia	Splosna bolnisnica Izola (Hospital of Izola)	Izola

Sponsors (9)

Lead Sponsor	Collaborator
Science and Research Centre Koper	Humanitas Hospital, Italy, University of Bari, University of Genova, University of L'Aquila, University of Padova, University of Pavia, University of Rome, University of Trieste

Country where clinical trial is conducted

Slovenia, 

References & Publications (9)

Šimunic B, Koren K, Rittweger J, Lazzer S, Reggiani C, Rejc E, Pišot 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. — View Citation

Floreani M, Rejc E, Taboga P, Ganzini A, Pišot R, Šimunic 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. — View Citation

Marušic U, Meeusen R, Pišot 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. Review. — View Citation

Marusic U, Giordani B, Moffat SD, Petric M, Dolenc P, Pišot 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. — View Citation

Marusic U, Kavcic V, Giordani B, Gerževic M, Meeusen R, Pišot 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. — View 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, Pišot 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. — View Citation

Pišot 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 Blenkuš M, Šimunic 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. — View 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. — View Citation

Rejc E, Floreani M, Taboga P, Botter A, Toniolo L, Cancellara L, Narici M, Šimunic B, Pišot 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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