Muscle Damage and Disuse Atrophy

In Young Healthy Males and Females, What is the Effect of Prior Eccentric Exercise on Thigh Muscle Atrophy During One Week of Leg Disuse Compared to no Prior Exercise?

Limb injury generally requires a period of recovery during which time the limb is often immobilised (e.g. with a cast or brace) resulting in a rapid loss of skeletal muscle. Despite the importance of muscle loss during injury, our understanding of how it occurs is incomplete. Several factors are likely to contribute, including a lack of muscle contraction and injury induced inflammation. In this study, the investigators will recruit healthy volunteers who will spend 7 days in a knee brace to replicate leg immobilisation. Prior to immobilisation, half of the participants will perform a single session of strenuous resistance exercise which is known to cause muscle damage and initiate an inflammatory response. This is designed to replicate the muscle damage and inflammation that occurs with injury. The remaining half of participants will not perform this exercise, allowing us to look at the additive effect of muscle damage and inflammation on muscle loss with immobilisation.

Study Overview

• Status: Completed
• Conditions: Muscle Disuse Atrophy
• Intervention / Treatment: Procedure: Eccentric exercise

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX1 2LU
      • University of Exeter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 - 40
• BMI between 18 and 27
• Healthy, recreationally active, non smoker

Exclusion Criteria:

• Non-removable metallic implants (including heart pacemaker, cochlear implants, medication pumps, surgical clips, plates or screws) or claustrophobia
• Use of nutritional supplements
• Chronic use of over the counter medication
• Any diagnosed metabolic disease (e.g. type 1 or 2 Diabetes).
• Any diagnosed cardiovascular disease or hypertension.
• Anyone with previous motor disorders. Anyone with a current musculoskeletal injury that may impair their use of crutches.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Immobilisation without prior exercise
Experimental: Muscle damage; 300 bilateral knee extensor eccentric contraction performed immediately prior to immobilisation	Procedure: Eccentric exercise; 300 eccentric contractions of the knee extensors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in thigh muscle volume from pre-immobilisation	The volume of the muscles comprising the thigh after 2 days of immobilisation will be compared to pre-immobilisation values. This will be measured using MRI.	After 2 days of immobilisation
Change in thigh muscle volume from pre-immobilisation	The volume of the muscles comprising the thigh after 7 days of immobilisation will be compared to pre-immobilisation values, and values obtained after 2 days of immobilisation. This will be measured using MRI.	After 7 days of immobilisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in unilateral knee extensor 1 repetition maximum	Unilateral knee extensor 1 repetition maximum will be measured before and after 7 days of single leg immobilisation using a weight stack leg extension machine	After 7 days of immobilisation
Change in unilateral knee extensor maximal voluntary torque production	Unilateral knee extensor maximal voluntary torque production will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.	After 7 days of immobilisation
Change in unilateral knee extensor isokinetic total work	Unilateral knee extensor total isokinetic work after 30 consecutive contractions will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.	After 7 days of immobilisation
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide	The enrichment of deuterated alanine (from the deuterium oxide heavy water stable isotope tracer) in vastus lateralis biopsy samples will be measured relative to the non-deuterated alanine. The change between pre-immobilisation and 2 days of immobilisation will be used to calculated a fractional synthetic rate (% day).	After 2 days of immobilisation
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide	The enrichment of deuterated alanine (from the deuterium oxide heavy water stable isotope tracer) in vastus lateralis biopsy samples will be measured relative to the non-deuterated alanine. The change between pre-immobilisation and 7 days of immobilisation will be used to calculated a fractional synthetic rate (% day).	After 7 days of immobilisation
Change in skeletal muscle gene expression	Skeletal muscle gene expression will be measured before and after 2 days of single leg immobilisation.	After 2 days of immobilisation
Change in skeletal muscle gene expression	Skeletal muscle gene expression will be measured before and after 7 days of single leg immobilisation.	After 7 days of immobilisation

Collaborators and Investigators

• Sponsor: University of Exeter

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): October 31, 2019

Study Registration Dates

• First Submitted: May 31, 2018
• First Submitted That Met QC Criteria: June 13, 2018
• First Posted (Actual): June 18, 2018

Study Record Updates

• Last Update Posted (Actual): September 27, 2021
• Last Update Submitted That Met QC Criteria: September 20, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Inflammation; Muscle damage; Immobilisation
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Pathological Conditions, Anatomical; Atrophy; Muscular Disorders, Atrophic
• Other Study ID Numbers: 171206/B/08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No