Disuse Atrophy (Muscle) of Lower Extremities, Muscle Function, Neuromuscular Electrical Stimulation, Myofibrillar Protein Synthesis
Conditions
Brief summary
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.
Interventions
OTHERBed rest
5 days of strict bed rest
OTHERNeuromuscular electrical stimulation
Unilateral neuromuscular electrical stimulation (m. Quadriceps)
Sponsors
Bispebjerg Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Masking description
The assessors will be without knowledge of which leg has received neuromuscular electrical stimulation and which leg was control
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy * Age between 18-30 or 65-80 years * Injury free in the lower extremities (No previous or current knee injuries or knee pain) * Normal weight * Consumes normal diet
Exclusion criteria
* Cognitive impairment affecting the ability to participate in the study. * Health related contraindications to participating in the intervention (i.e., bed rest and/or NMES), such as eczema and rash on the lower extremities * Smoker * Obesity * Not able to speak or understand Danish. * Acute or chronic diseases such as diabetes, cancer, embolism, infection, cardio-vascular diseases * Use of medication which affects myofibrillar protein synthesis or the skeletal muscle tissue * Use of other medication (e.g. anticoagulants, adrenal cortex hormone \[within the last 3 months\] etc.) * Previous or current use of anabolic steroids * Previous participation in research trials involving deuterium oxide or another stable isotope tracer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in maximal isometric muscle strength and superimposed twitch | Change from baseline after bed rest intervention | Maximal isometric voluntary quadriceps strength combined with the superimposed twitch technique to assess maximal strength and voluntary muscle activation |
| Change in Myofiber cross-sectional area | Change from baseline after bed rest intervention | Histochemical analysis of type I and type II myofiber cross-sectional area |
| Assessment of myofibrillar protein synthesis | 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) | Quantification of myofibrillar protein synthesis using the stable-isotope amino acid tracer deuterium oxide (D2O) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in total MuRF-1 protein assessed by Western blot | Change from baseline after bed rest intervention | Assessment of MuRF-1 protein by Western Blot analysis using muscle tissue from vastus lateralis |
| Change in total Atrogin-1 protein assessed by Western blot | Change from baseline after bed rest intervention | Assessment of Atrogin-1 protein by Western Blot analysis using muscle tissue from vastus lateralis |
| Change in total myostatin protein assessed by Western blot | Change from baseline after bed rest intervention | Assessment of myostatin protein by Western Blot analysis using muscle tissue from vastus lateralis |
| Change in quadriceps muscle morphology and architecture by ultrasound scan | Change from baseline after bed rest intervention | Ultrasound scan of rectus femoris and vastus lateralis muscle thickness and of vastus lateralis pennation angle |
| Change in body composition by DEXA scan | Change from baseline after bed rest intervention | Assessment of whole body and regional lean mass and fat |
| Change in sway - postural balance | Change from baseline after bed rest intervention | Measurement of displacement of center of pressure during unilateral and bilateral stance |
| Change in triglycerides | Day 0, day 2, day 4 and day 5 | Fasting blood samples are collected for analysis of triglycerides |
| Change in cholesterol | Day 0, day 2, day 4 and day 5 | Fasting blood samples are collected for later analysis of cholesterol |
| Change in C-reactive protein (CRP) | Day 0, day 2, day 4 and day 5 | Fasting blood samples are collected for analysis of CRP values |
| Change in leg extensor power | Change from baseline after bed rest intervention | Muscle power of the lower extremities assessed using the Nottingham power rig |
| Change in total Akt protein assessed by Western blot | Change from baseline after bed rest intervention | Assessment of Akt protein by Western Blot analysis using muscle tissue from vastus lateralis |
| Change in total mTOR protein assessed by Western blot | Change from baseline after bed rest intervention | Assessment of mTOR protein by Western Blot analysis using muscle tissue from vastus lateralis |
Other
| Measure | Time frame | Description |
|---|---|---|
| Accelerometer data | 3 days prior to the intervention | Collecting accelerometer data to quantify habitual activities prior to bed rest period |
Countries
Denmark
Contacts
Primary ContactSofie K Hansen
Outcome results
None listed