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Loss of muscle mass is common phenotypic trait of muscular disuse and ageing. The loss of muscle mass affects, among others, the ability to maintain homeostasis of glucose metabolism and the energy reservoir in catabolic conditions, while also affecting mechanical muscle function which can cause detrimental impairments in general functional status and hence quality of life.
However, a limited amount of research has attempted to elucidate molecular regulators of muscle mass loss following bed rest in older individuals and across genders. Consequently, the mechanistic drivers are unresolved and there are currently no effective therapeutic strategies to counteract muscle wasting and loss of function in individuals submitted to bed rest e.g. during hospitalization.
Purpose The purpose is to examine the effects of 5 days of bed rest on muscle mass, including myofibrillar protein synthesis and breakdown, and muscle function, and elucidate molecular regulators of muscle mass loss and metabolic pathways, while also investigating if potential negative effects can be counteracted by daily NeuroMuscular Electrical Stimulation (NMES) across different age and genders.
Methods The study is designed as a randomized controlled cross-over 5-day bed rest study including a group of healthy young (18-30 years) and healthy old (65-80 years) men and women.
Participants will receive daily electrical stimulation (NMES) of the thigh muscles (30 min x 3/day) on one leg (ES), while the other leg serves as a control (CON).
Participants will be tested at baseline (pre) and after (post) intervention for muscle strength, muscle power, balance, and muscle activation. Blood samples are collected at several time points and muscle biopsies are sampled pre- and post-intervention along with assessment of whole-body muscle mass and thigh muscle mass.
Scientific exposition The results from the study can potentially provide insight into the adaptive mechanisms associated with NMES training and muscular disuse on both cellular- and whole-body level. The understanding of the underlying mechanisms is crucial for the application of NMES in a therapeutic context and will furthermore help us understand the basic mechanism regulating the skeletal muscle mass during both training and muscular disuse.
Overall, the results can potentially help establishing treatments to counteract loss of muscle mass, muscle function and muscle health during periods of muscular disuse.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bed rest- Control | Active Comparator | One leg will be subjected to disuse by bed rest and will not receive further treatment during the bed rest period. |
|
| Bed rest + NMES | Experimental | One leg will be subjected to disuse by bed rest and will in addition receive neuromuscular electrical stimulation of the quadriceps muscle 3 times/day. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bed rest | Other | 5 days of strict bed rest |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Myofiber cross-sectional area | Histochemical analysis of type I and type II myofiber cross-sectional area | Change from baseline after bed rest intervention |
| Assessment of myofibrillar protein synthesis | Quantification of myofibrillar protein synthesis using the stable-isotope amino acid tracer deuterium oxide (D2O) | Assessed during the period from pre-intervention biopsies (day 0, first day of bed rest) to post-intervention biopsies (day 5, last day and cessation of bed rest) |
| Change in maximal isometric muscle strength and superimposed twitch | Maximal isometric voluntary quadriceps strength combined with the superimposed twitch technique to assess maximal strength and voluntary muscle activation | Change from baseline after bed rest intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in total Akt protein assessed by Western blot | Assessment of Akt protein by Western Blot analysis using muscle tissue from vastus lateralis | Change from baseline after bed rest intervention |
| Change in total mTOR protein assessed by Western blot |
| Measure | Description | Time Frame |
|---|---|---|
| Accelerometer data | Collecting accelerometer data to quantify habitual activities prior to bed rest period | 3 days prior to the intervention |
| Accelerometer data | Collecting accelerometer data to monitor activity throughout the intervention |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sofie K Hansen | Contact | 0045 22423877 | sofie.krarup.hansen.01@regionh.dk |
| Name | Affiliation | Role |
|---|---|---|
| Charlotte Suetta, Professor | Bispebjerg Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bispebjerg Hospital | Recruiting | Copenhagen | 2400 | Denmark |
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| ID | Term |
|---|---|
| D020966 | Muscular Disorders, Atrophic |
| ID | Term |
|---|---|
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D001510 | Bed Rest |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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Participants are subjected to 5 days bed rest. One leg will receive 3/daily neuromuscular electrical stimulation. The contralateral leg will serve as control-leg undergo disuse only.
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The assessors will be without knowledge of which leg has received neuromuscular electrical stimulation and which leg was control
| Neuromuscular electrical stimulation |
| Other |
Unilateral neuromuscular electrical stimulation (m. Quadriceps) |
|
Assessment of mTOR protein by Western Blot analysis using muscle tissue from vastus lateralis |
| Change from baseline after bed rest intervention |
| Change in total MuRF-1 protein assessed by Western blot | Assessment of MuRF-1 protein by Western Blot analysis using muscle tissue from vastus lateralis | Change from baseline after bed rest intervention |
| Change in total Atrogin-1 protein assessed by Western blot | Assessment of Atrogin-1 protein by Western Blot analysis using muscle tissue from vastus lateralis | Change from baseline after bed rest intervention |
| Change in total myostatin protein assessed by Western blot | Assessment of myostatin protein by Western Blot analysis using muscle tissue from vastus lateralis | Change from baseline after bed rest intervention |
| Change in quadriceps muscle morphology and architecture by ultrasound scan | Ultrasound scan of rectus femoris and vastus lateralis muscle thickness and of vastus lateralis pennation angle | Change from baseline after bed rest intervention |
| Change in body composition by DEXA scan | Assessment of whole body and regional lean mass and fat | Change from baseline after bed rest intervention |
| Change in leg extensor power | Muscle power of the lower extremities assessed using the Nottingham power rig | Change from baseline after bed rest intervention |
| Change in sway - postural balance | Measurement of displacement of center of pressure during unilateral and bilateral stance | Change from baseline after bed rest intervention |
| Change in triglycerides | Fasting blood samples are collected for analysis of triglycerides | Day 0, day 2, day 4 and day 5 |
| Change in cholesterol | Fasting blood samples are collected for later analysis of cholesterol | Day 0, day 2, day 4 and day 5 |
| Change in C-reactive protein (CRP) | Fasting blood samples are collected for analysis of CRP values | Day 0, day 2, day 4 and day 5 |
| Throughout the 5 day intervention |