Queen's Univeristy
Kingston, Ontario, K7L 3N6, Canada
Location status: Recruiting
NCT Number: NCT07178353
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:
* Magnetic resonance imaging of the thigh muscles * Strength testing of the thigh muscles * Insulin sensitivity testing in response to a mixed meal * Exogenous glucose oxidation in response to a mixed meal * Muscle biopsies from the thigh muscles * Blood samples
Interested in participating?
Request Info18 year–30 year
All sexes
Interventional
Not applicable
Kingston, Ontario, K7L 3N6, Canada
Location status: Recruiting
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.
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
5 days of strict bedrest. Participants are allowed to sit up in bed, but will perform any bathing or bathroom activities in a wheelchair.
Other names: Horizontal Bedrest
Time frame: Day 0, and 5
Quadriceps muscle volume will be assessed by magnetic resonance imaging.
Time frame: Day -14, -9, and 5
Knee extensor peak torque will be assessed using dynamometry
Time frame: Day -14, -9, and 5
Peak isotonic power determined at 30% maximal isometric voluntary contraction torque using a dynamometer
Time frame: Day -14, -9, and 5
Knee extensor fatiguability will be determined by the decrease in isotonic power across 40 contractions at 30% MVC using dynamometry.
Time frame: Day 0 and 5
Change in quadriceps muscle cross sectional area measured by magnetic resonance imaging scan.
Time frame: 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.
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.
Time frame: Aggregate 2-hour window on day -5, 0, and 5
Determination of the total rise in plasma glucose during a mixed meal tolerance test, to be assessed by an enzyme-linked immunosorbent assay.
Time frame: Aggregate 2-hours on day -5, 0, and 5
Determination of the total rise in plasma insulin during a mixed meal tolerance test, to be assessed by an enzyme-linked immunosorbent assay.
Time frame: Aggregate 3 hours during the mixed meal tolerance test on day -5, 0, and 5
Measurement of 13C excretion in breath samples using isotope ratio mass spectrometry.
Time frame: 2-hours on day -5, 0, and 5
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.
Time frame: Day -5, 1, 3, and 5
Mitochondrial respiration will be assessed using an Oroboros Oxygraph 2000.
Time frame: Day 0, 1, 3, and 5
Activation of translational factors involved in skeletal muscle protein synthesis assessed by western blotting.
Time frame: 2-hour mixed meal tolerance test on day -5, 0, and 5
Plasma glucose concentration measured during a mixed meal tolerance test.
Time frame: 2-hour mixed meal tolerance test on day -5, 0, and 5
Serum insulin concentration measured during a mixed meal tolerance test
Time frame: 2-hour mixed meal tolerance test on day -5, 0, and 5
Peak glucose concentration measured during a mixed meal tolerance test
Time frame: 2-hour mixed meal tolerance test on day -5, 0, and 5
Peak insulin concentration measured during a mixed meal tolerance test.
Time frame: Day 0, 1, 3, and 5
Imaging of subsarcolemmal and intermyofibrillar mitochondria to assess change in mitochondrial content from bedrest.
Time frame: Day 0, 5
Orthostatic blood pressure assessment pre and post bedrest, and following recovery after bedrest
Time frame: Day -5, 0, and 5
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
Contact information is provided by the study sponsor or research team.
Queen's University
Other
Changes in Muscle Mass, Strength, and Muscle Protein Synthesis in Response to 5 Days of Bedrest in Young, Healthy Adults
Acronym: FABRIC
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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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