The Regulation of Human Skeletal Muscle Mass by Contractile Perturbation

Study Overview
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Brief Summary
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It is well known that periods of weight training lead to increases in skeletal muscle size and strength. In contrast, periods of inactivity such as bed rest or immobilization result in losses of skeletal muscle size and strength. However, individuals experience variable magnitudes of muscle size change in response to changes in mechanical tension, such that certain individuals experience large changes in muscle mass whereas others do not. What is not currently known, and will be the primary goal of the present investigation, is to determine whether individuals who gain the most muscle mass with exercise training also lose the most muscle when they are immobilized. The investigators hypothesize that individuals who gain the most muscle with training will also lose the most with immobilization.

Detailed Description
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Resistance exercise, paired with protein ingestion, leads to the accretion of muscle proteins that over time results in the augmentation of muscle size and muscle strength. By virtue of its ability to stimulate increases in muscle size and strength, resistance exercise is an effective method that can be used by healthcare practitioners to promote the recovery of lost muscle mass resulting from a period of immobilization (resulting from broken bones, elective surgery, etc.). However, while exercise in general is an effective therapeutic strategy to combat muscle loss and frailty, the extent to which individuals respond to resistance exercise is highly variable. Some individuals exhibit large changes in muscle size (high responders) whereas other exhibit little to no change (low responders). Thus, where as one resistance exercise program might be an appropriate treatment for one individual following disuse, another individual might require a greater stimulus and/or pharmaceutical assistance in order to fully recover. What is currently unknown is whether individuals who experience the most profound increases in skeletal muscle mass following resistance exercise also lose the most muscle upon limb immobilization. Answering this gap in our knowledge will be the primary goal of this study. The procurement of this knowledge will hopefully permit the development of individualized exercise programs that can be used to influence the recovery of skeletal muscle that is lost with inactivity and immobilization.

Official Title
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The Regulation of Human Skeletal Muscle Mass by Contractile Perturbation

Conditions
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Muscle Atrophy, Disuse Atrophy (Muscle) of Lower Leg

Intervention / Treatment
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* Other: Unilateral Resistance Exercise
* Procedure: Immobilization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Non-Smoker Do not heavily consume alcohol Exclusion Criteria: Female Younger than 18, or older than 30 years use of anti-inflammatory or analgesic medication history of neuromuscular disorders family history of deep vein thrombosis regularly take part in structured physical exercise (greater than 2 days per week) take any medications known to influence protein metabolism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

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: Single Group Assignment
Interventional Model Description: The model will be a within-subject intervention. Each subject will have one leg randomized to unilateral resistance exercise (for 10 weeks) and the other to immobilization (for the last 2 weeks of the study).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unilateral Resistance Exercise<br>One of the participant's legs will be randomized to a unilateral resistance training arm for 10 weeks in duration. The leg chosen to be trained will undergo resistance exercise three days per week (Monday, Wednesday, and Friday) for the entirety of the study. | Other: Unilateral Resistance Exercise<br>* Unilateral Resistance exercise will include training three days per week and each session will include 3 sets of leg extension and 3 sets of leg press. In each set, the participant will complete a maximum of 12 repetitions.<br>* Other names: Resistance training;|
| Experimental: Immobilization<br>One of the participant's legs will be chosen to be immobilized during the last two weeks of the study. Therefore, one leg will be resistance exercising from week 0-10 whereas the other leg will be immobilized during weeks 8-10. | Procedure: Immobilization<br>* During the last two weeks of the study (week 8-10), a Don Joy adjustable knee brace will be applied to the participant's leg randomized to immobilization. The brace will be applied at a 40 degree angle relative to complete extension.<br>* Other names: Knee Bracing;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Cross Sectional Area | The changes in muscle cross sectional area will be assessed pre-training (week 0) and post training/immobilization (week 10) using magnetic resonance imaging (MRI). Muscle cross-sectional area will be assessed over a continuous period of 7 months. | May 2017 - Dec 2017 | 
| Leg Lean Mass | The changes in leg lean mass will be assessed pre-training (week 0) and post-training/immobilization using dual energy x-ray absorptiometry. Leg lean mass measurements will be made over a continuous period of 7 months. | May 2017 - Dec 2017 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal Muscle Gene Expression | Gene expression will be quantified pre-training (week 0) and post-training/immobilization from muscle tissue samples obtained via muscle biopsies in both legs. Gene expression assessment will take place over a continuous period of 7 months. | May 2017 - Dec 2017 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle Hypertrophy, Muscle Atrophy, Resistance Training, Immobilization