The Impact of Bed Rest, Aging and NMES on Skeletal Muscle

Muscle Function Clinical Trial

Official title:

The Impact of Bed Rest and Aging on Muscle Mass and Muscle Function: Effects of Neuromuscular Electrical Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05617222
• Other study ID #: H-20038614
• Status: Recruiting
• Phase: N/A
• Start date: April 29, 2022
• Est. completion date: August 1, 2024

Study information

• Verified date: November 2022
• Source: Bispebjerg Hospital
• Contact: Sofie K Hansen
• Phone: 0045 22423877
• Email: sofie.krarup.hansen.01[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: August 1, 2024
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscle Function
• Muscular Disorders, Atrophic
• Neuromuscular Electrical Stimulation

Intervention

Other:
• Bed rest
5 days of strict bed rest
• Neuromuscular electrical stimulation
Unilateral neuromuscular electrical stimulation (m. Quadriceps)

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Bispebjerg Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Accelerometer data	Collecting accelerometer data to quantify habitual activities prior to bed rest period	3 days prior to the intervention
Other	Accelerometer data	Collecting accelerometer data to monitor activity throughout the intervention	Throughout the 5 day intervention
Primary	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
Primary	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)
Primary	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
Secondary	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
Secondary	Change in total mTOR protein assessed by Western blot	Assessment of mTOR protein by Western Blot analysis using muscle tissue from vastus lateralis	Change from baseline after bed rest intervention
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in body composition by DEXA scan	Assessment of whole body and regional lean mass and fat	Change from baseline after bed rest intervention
Secondary	Change in leg extensor power	Muscle power of the lower extremities assessed using the Nottingham power rig	Change from baseline after bed rest intervention
Secondary	Change in sway - postural balance	Measurement of displacement of center of pressure during unilateral and bilateral stance	Change from baseline after bed rest intervention
Secondary	Change in triglycerides	Fasting blood samples are collected for analysis of triglycerides	Day 0, day 2, day 4 and day 5
Secondary	Change in cholesterol	Fasting blood samples are collected for later analysis of cholesterol	Day 0, day 2, day 4 and day 5
Secondary	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