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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
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The goal of this intervention trial is to characterize skeletal muscle atrophy in healthy, young adults during short term bedrest. The main questions it aims to answer are:
How much do skeletal muscle volume, strength, and fatigue resistance decline during bedrest? How much does whole-body insulin sensitivity change during bedrest? How do mitochondrial function and protein synthesis change during bedrest?
Participants will undergo the following tests before and after a free-living control period and before and after a 5 day period of strict horizontal bedrest:
Skeletal muscle plays a critical role in physical function and metabolic health, with its maintenance driven by the balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). During periods of disuse, such as illness or injury, MPS declines while MPB remains relatively unchanged, leading to muscle loss and atrophy. Short-term disuse, such as bedrest, is commonly experienced through hospitalization, and can result in rapid declines in muscle mass and strength, typically affecting the lower limbs to a greater extent. At the molecular level, bed rest significantly reduces MPS, with durations as little as 3 days showing drastic impairment in skeletal muscle turnover. Additionally, short-term periods of disuse have shown to blunt mitochondrial respiration, affecting the ability for skeletal muscle to produce energy for proper funcitoning and metabolic processes. Diminished skeletal muscle metabolic function directly impacts whole-body metabolic health. Periods of bedrest between 5 and 7 days have shown to decrease whole-body glucose tolerance, increase insulin resistance, and decrease insulin-stimulated leg glucose uptake. All together, these contribute to decreased skeletal muscle mass and strength, and diminished metabolic function, contributing to a decline in overall physical function, health, and well-being. Current studies on short-term bed rest (ex. 5 days) in young adults are limited, and existing research has focused on simulated microgravity models rather than horizontal bed rest, which better represents clinical scenarios. Additionally, no study to our knowledge has explored how the molecular mechanisms that drive MPS change over the course of a 5-day bedrest period. This highlights a need to explore if there are differences in the attrition of synthesis rates of the different protein pools in skeletal muscle (ex. myofibrillar, sarcoplasmic, and mitochondrial).
The purpose of the present study is to investigate changes in leg muscle mass, strength, and whole-body insulin sensitivity over five days of bed rest, as well as examine the time-course changes in molecular mechanisms underlying skeletal muscle turnover. The investigators hypothesize that, compared to the control period, quadriceps muscle size (volume and cross-sectional area), strength/power/fatigue resistance, and whole-body insulin sensitivity will decrease following bedrest. The investigators hypothesize that these outcomes will be linked to decreases in mitochondrial respiratory function and impaired fractional synthetic rates of muscle proteins.
In this repeated-measures design, participants will undergo a five day baseline control period followed by five days of bed rest to compare changes from bedrest to their own free-living control period.
Findings from this study will help inform future research on the impact of short-term, clinically-relevant, bedrest in young adults and aid in the development of targeted interventions to mitigate declines in muscle mass from occurring from acute bouts of muscle disuse.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental: Bedrest | Experimental | 19 day study period, consisting of baseline testing, 5 days of free-living (habitual daily activities) immediately followed by 5 days of strict bedrest. Diet controlled and physical activity monitored for entire study period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bedrest | Other | 5 days of strict bedrest. Participants are allowed to sit up in bed, but will perform any bathing or bathroom activities in a wheelchair. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Quadriceps muscle volume | Quadriceps muscle volume will be assessed by magnetic resonance imaging. | Day 0, and 5 |
| Measure | Description | Time Frame |
|---|---|---|
| Muscle strength | Knee extensor peak torque will be assessed using dynamometry | Day -14, -9, and 5 |
| Knee extensor power | Peak isotonic power determined at 30% maximal isometric voluntary contraction torque using a dynamometer |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chris McGlory, PhD. | Contact | 6135336000 | 75410 | chris.mcglory@queensu.ca |
| Name | Affiliation | Role |
|---|---|---|
| Chris McGlory, PhD. | Queen's University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Queen's Univeristy | Recruiting | Kingston | Ontario | K7L 3N6 | Canada |
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| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D007333 | Insulin Resistance |
| D020966 | Muscular Disorders, Atrophic |
| ID | Term |
|---|---|
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
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| ID | Term |
|---|---|
| D001510 | Bed Rest |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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This study uses a within-subjects, repeated measures design. Single-arm study. Participants will complete a 5-day free-living, baseline testing period, before undergoing 5 days of strict horizontal bedrest.
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|
| Day -14, -9, and 5 |
| Muscle fatiguability | Knee extensor fatiguability will be determined by the decrease in isotonic power across 40 contractions at 30% MVC using dynamometry. | Day -14, -9, and 5 |
| Muscle cross-sectional area | Change in quadriceps muscle cross sectional area measured by magnetic resonance imaging scan. | Day 0 and 5 |
| Muscle protein synthesis | Muscle protein synthesis measured as fractional synthesis rate of the myofibrillar, sarcoplasmic, and mitochondrial protein pools within skeletal muscle. These 3 pools will be assessed using combined protocol of skeletal muscle biopsy, stable isotope tracing, cavity ring down spectroscopy with liquid isotope analysis, and gas-chromatography pyrolysis isotope-ratio mass spectrometry. | Day -5 to 0, day 0 to 1, day 0 to 3, day 0 to 5, day 1 to 3, day 1 to 5, and day 3 to 5. |
| 2-hour plasma glucose incremental area under the curve | Determination of the total rise in plasma glucose during a mixed meal tolerance test, to be assessed by an enzyme-linked immunosorbent assay. | Aggregate 2-hour window on day -5, 0, and 5 |
| 2- hour plasma insulin incremental area under the curve | Determination of the total rise in plasma insulin during a mixed meal tolerance test, to be assessed by an enzyme-linked immunosorbent assay. | Aggregate 2-hours on day -5, 0, and 5 |
| Postprandial glucose oxidation | Measurement of 13C excretion in breath samples using isotope ratio mass spectrometry. | Aggregate 3 hours during the mixed meal tolerance test on day -5, 0, and 5 |
| Matsuda Index | Insulin sensitivity measured via the Matsuda Index during a mixed meal tolerance test. Matsuda index values <4.0 indicate insulin resistance, with higher values representing insulin sensitivity. | 2-hours on day -5, 0, and 5 |
| Mitochondrial Respiratory Function | Mitochondrial respiration will be assessed using an Oroboros Oxygraph 2000. | Day -5, 1, 3, and 5 |
| Expression of Translational Factors Related to Skeletal Muscle Protein Synthesis | Activation of translational factors involved in skeletal muscle protein synthesis assessed by western blotting. | Day 0, 1, 3, and 5 |
| Plasma glucose concentration | Plasma glucose concentration measured during a mixed meal tolerance test. | 2-hour mixed meal tolerance test on day -5, 0, and 5 |
| Serum insulin concentration | Serum insulin concentration measured during a mixed meal tolerance test | 2-hour mixed meal tolerance test on day -5, 0, and 5 |
| Peak glucose concentration | Peak glucose concentration measured during a mixed meal tolerance test | 2-hour mixed meal tolerance test on day -5, 0, and 5 |
| Peak insulin concentration | Peak insulin concentration measured during a mixed meal tolerance test. | 2-hour mixed meal tolerance test on day -5, 0, and 5 |
| Transmission Electron Microscopy Analysis | Imaging of subsarcolemmal and intermyofibrillar mitochondria to assess change in mitochondrial content from bedrest. | Day 0, 1, 3, and 5 |
| Supine to Stand Test | Orthostatic blood pressure assessment pre and post bedrest, and following recovery after bedrest | Day 0, 5 |
| Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | Insulin resistance assessed using fasting insulin and glucose levels. Values <1.0 indicate insulin sensitivity, >1.9 and < 2.9 indicates early insulin resistance, and values >2.9 indicate significant insulin resistance | Day -5, 0, and 5 |
| D020763 |
| Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |