Clinical trial NCT05617222: The Impact of Bed Rest, Aging and NMES on Skeletal Muscle
Official title: The Impact of Bed Rest and Aging on Muscle Mass and Muscle Function: Effects of Neuromuscular Electrical Stimulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Disuse Atrophy (Muscle) of Lower Extremities
Muscle Function
Neuromuscular Electrical Stimulation
Myofibrillar Protein Synthesis
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
First posted: 2022-11-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Myofiber cross-sectional area
timeFrame: Change from baseline after bed rest intervention
measure: Assessment of myofibrillar protein synthesis
timeFrame: 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)
measure: Change in maximal isometric muscle strength and superimposed twitch
timeFrame: Change from baseline after bed rest intervention
Secondary outcomes:
measure: Change in total Akt protein assessed by Western blot
timeFrame: Change from baseline after bed rest intervention
measure: Change in total mTOR protein assessed by Western blot
timeFrame: Change from baseline after bed rest intervention
measure: Change in total MuRF-1 protein assessed by Western blot
timeFrame: Change from baseline after bed rest intervention
measure: Change in total Atrogin-1 protein assessed by Western blot
timeFrame: Change from baseline after bed rest intervention
measure: Change in total myostatin protein assessed by Western blot
timeFrame: Change from baseline after bed rest intervention
measure: Change in quadriceps muscle morphology and architecture by ultrasound scan
timeFrame: Change from baseline after bed rest intervention
measure: Change in body composition by DEXA scan
timeFrame: Change from baseline after bed rest intervention
measure: Change in leg extensor power
timeFrame: Change from baseline after bed rest intervention
measure: Change in sway - postural balance
timeFrame: Change from baseline after bed rest intervention
measure: Change in triglycerides
timeFrame: Day 0, day 2, day 4 and day 5
measure: Change in cholesterol
timeFrame: Day 0, day 2, day 4 and day 5
measure: Change in C-reactive protein (CRP)
timeFrame: Day 0, day 2, day 4 and day 5
Other outcomes:
measure: Accelerometer data
timeFrame: 3 days prior to the intervention
measure: Accelerometer data
timeFrame: Throughout the 5 day intervention
Locations:
city: Copenhagen
country: Denmark
facility: Bispebjerg Hospital
Study officials:
affiliation: Bispebjerg Hospital
name: Charlotte Suetta, Professor
role: PRINCIPAL_INVESTIGATOR
References: