Muscle Damage and Disuse Atrophy

Study Overview
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Brief Summary
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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.

Official Title
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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?

Conditions
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Muscle Disuse Atrophy

Intervention / Treatment
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* Procedure: Eccentric exercise


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle damage, Inflammation, Immobilisation