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

Primary Purpose

Disuse Atrophy (Muscle) of Lower Extremities, Muscle Function, Neuromuscular Electrical Stimulation

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Bed rest
Neuromuscular electrical stimulation
Sponsored by
Bispebjerg Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Disuse Atrophy (Muscle) of Lower Extremities

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Bispebjerg HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Bed rest- Control

Bed rest + NMES

Arm Description

One leg will be subjected to disuse by bed rest and will not receive further treatment during the bed rest period.

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.

Outcomes

Primary Outcome Measures

Change in Myofiber cross-sectional area
Histochemical analysis of type I and type II myofiber cross-sectional area
Assessment of myofibrillar protein synthesis
Quantification of myofibrillar protein synthesis using the stable-isotope amino acid tracer deuterium oxide (D2O)
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

Secondary Outcome Measures

Change in total Akt protein assessed by Western blot
Assessment of Akt protein by Western Blot analysis using muscle tissue from vastus lateralis
Change in total mTOR protein assessed by Western blot
Assessment of mTOR protein by Western Blot analysis using muscle tissue from vastus lateralis
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 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 in total myostatin protein assessed by Western blot
Assessment of myostatin protein by Western Blot analysis using muscle tissue from vastus lateralis
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 in body composition by DEXA scan
Assessment of whole body and regional lean mass and fat
Change in leg extensor power
Muscle power of the lower extremities assessed using the Nottingham power rig
Change in sway - postural balance
Measurement of displacement of center of pressure during unilateral and bilateral stance
Change in triglycerides
Fasting blood samples are collected for analysis of triglycerides
Change in cholesterol
Fasting blood samples are collected for later analysis of cholesterol
Change in C-reactive protein (CRP)
Fasting blood samples are collected for analysis of CRP values

Full Information

First Posted
August 22, 2022
Last Updated
November 14, 2022
Sponsor
Bispebjerg Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05617222
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 29, 2022 (Actual)
Primary Completion Date
February 28, 2023 (Anticipated)
Study Completion Date
August 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bispebjerg Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Disuse Atrophy (Muscle) of Lower Extremities, Muscle Function, Neuromuscular Electrical Stimulation, Myofibrillar Protein Synthesis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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.
Masking
Outcomes Assessor
Masking Description
The assessors will be without knowledge of which leg has received neuromuscular electrical stimulation and which leg was control
Allocation
Randomized
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bed rest- Control
Arm Type
Active Comparator
Arm Description
One leg will be subjected to disuse by bed rest and will not receive further treatment during the bed rest period.
Arm Title
Bed rest + NMES
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Bed rest
Intervention Description
5 days of strict bed rest
Intervention Type
Other
Intervention Name(s)
Neuromuscular electrical stimulation
Intervention Description
Unilateral neuromuscular electrical stimulation (m. Quadriceps)
Primary Outcome Measure Information:
Title
Change in Myofiber cross-sectional area
Description
Histochemical analysis of type I and type II myofiber cross-sectional area
Time Frame
Change from baseline after bed rest intervention
Title
Assessment of myofibrillar protein synthesis
Description
Quantification of myofibrillar protein synthesis using the stable-isotope amino acid tracer deuterium oxide (D2O)
Time Frame
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)
Title
Change in maximal isometric muscle strength and superimposed twitch
Description
Maximal isometric voluntary quadriceps strength combined with the superimposed twitch technique to assess maximal strength and voluntary muscle activation
Time Frame
Change from baseline after bed rest intervention
Secondary Outcome Measure Information:
Title
Change in total Akt protein assessed by Western blot
Description
Assessment of Akt protein by Western Blot analysis using muscle tissue from vastus lateralis
Time Frame
Change from baseline after bed rest intervention
Title
Change in total mTOR protein assessed by Western blot
Description
Assessment of mTOR protein by Western Blot analysis using muscle tissue from vastus lateralis
Time Frame
Change from baseline after bed rest intervention
Title
Change in total MuRF-1 protein assessed by Western blot
Description
Assessment of MuRF-1 protein by Western Blot analysis using muscle tissue from vastus lateralis
Time Frame
Change from baseline after bed rest intervention
Title
Change in total Atrogin-1 protein assessed by Western blot
Description
Assessment of Atrogin-1 protein by Western Blot analysis using muscle tissue from vastus lateralis
Time Frame
Change from baseline after bed rest intervention
Title
Change in total myostatin protein assessed by Western blot
Description
Assessment of myostatin protein by Western Blot analysis using muscle tissue from vastus lateralis
Time Frame
Change from baseline after bed rest intervention
Title
Change in quadriceps muscle morphology and architecture by ultrasound scan
Description
Ultrasound scan of rectus femoris and vastus lateralis muscle thickness and of vastus lateralis pennation angle
Time Frame
Change from baseline after bed rest intervention
Title
Change in body composition by DEXA scan
Description
Assessment of whole body and regional lean mass and fat
Time Frame
Change from baseline after bed rest intervention
Title
Change in leg extensor power
Description
Muscle power of the lower extremities assessed using the Nottingham power rig
Time Frame
Change from baseline after bed rest intervention
Title
Change in sway - postural balance
Description
Measurement of displacement of center of pressure during unilateral and bilateral stance
Time Frame
Change from baseline after bed rest intervention
Title
Change in triglycerides
Description
Fasting blood samples are collected for analysis of triglycerides
Time Frame
Day 0, day 2, day 4 and day 5
Title
Change in cholesterol
Description
Fasting blood samples are collected for later analysis of cholesterol
Time Frame
Day 0, day 2, day 4 and day 5
Title
Change in C-reactive protein (CRP)
Description
Fasting blood samples are collected for analysis of CRP values
Time Frame
Day 0, day 2, day 4 and day 5
Other Pre-specified Outcome Measures:
Title
Accelerometer data
Description
Collecting accelerometer data to quantify habitual activities prior to bed rest period
Time Frame
3 days prior to the intervention
Title
Accelerometer data
Description
Collecting accelerometer data to monitor activity throughout the intervention
Time Frame
Throughout the 5 day intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sofie K Hansen
Phone
0045 22423877
Email
sofie.krarup.hansen.01@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charlotte Suetta, Professor
Organizational Affiliation
Bispebjerg Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bispebjerg Hospital
City
Copenhagen
ZIP/Postal Code
2400
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sofie K Hansen, Mac
Phone
22423877
Ext
0045
Email
sofie.krarup.hansen.01@regionh.dk

12. IPD Sharing Statement

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

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