An interventional study of Knee immobilization brace (0°) for 5 days and Knee immobilization brace (60°) for 5 days in Muscle Atrophy, Disuse Atrophy and Immobilization, sponsored by Wageningen University. Not yet recruiting. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-08.
Sponsored by Wageningen University · Not applicable, Interventional, and Basic science
This study looks at what happens to leg muscles when the knee is kept straight or bent during five days of wearing a brace. We want to find out if keeping the knee bent (so the thigh muscle is stretched) helps prevent muscle loss compared to keeping the knee straight. Thirty healthy adults will take part. They will wear a knee brace for five days and have several tests before and after, including scans, blood samples, and small muscle samples. The results may help doctors find better ways to protect muscles when people cannot move, for example after surgery or illness.
Short periods of physical inactivity, as occur during illness, surgery, or injury, lead to rapid and substantial losses of muscle mass, strength, and metabolic health, often with incomplete recovery in vulnerable individuals. In older adults, repeated bouts of disuse are thought to contribute significantly to age-related sarcopenia. Despite decades of research, the underlying mechanisms remain incompletely elucidated, and effective therapeutic interventions are lacking.
Mechanistically, any muscle atrophy must occur due to a negative muscle protein net balance (MPNB), which can be caused by a decline in muscle protein synthesis (MPS), an increase in muscle protein breakdown (MPB), or a combination of both. Normally, exercise and dietary protein stimulate MPS and maintain muscle mass. During disuse, however, exercise is often impossible, and inactive muscle shows a blunted response to dietary protein. Consequently, these potent strategies become ineffective or even harmful in inactive individuals, highlighting the need for alternative approaches.
Animal studies indicate that immobilizing a muscle in a lengthened (stretched) position can attenuate disuse-induced muscle atrophy and functional decline compared to a shortened position. Whether this phenomenon also occurs in humans, and whether passive muscle length and tension influence muscle metabolism during disuse, remain unexplored.
The objective of this study is to assess whether immobilizing the quadriceps in a lengthened versus neutral position during disuse attenuates losses of muscle mass, function, and metabolic health.
In this randomized, controlled human intervention study with 2 parallel groups 30 healthy, normal weight males and females (18-40 years old, BMI between 18 and 30 kg·m-2) will undergo 5 days of unilateral leg immobilization using a knee brace that prevents voluntary quadriceps contraction. In the neutral group, the leg is fixed in full extension (0° flexion), while in the lengthened group it is fixed at 60° flexion, stretching the quadriceps.
The effects on muscle protein net balance (MPNB), quadriceps muscle volume , muscle quality, muscle strength, fatigue resistance, and muscle mitochondrial bioenergetics will be assessed.
Exclusion Criteria:
Participants in this group wear a knee brace in full extension (0°) for five consecutive days.
Device: Knee immobilization brace (0°) for 5 days
Participants in this group wear a knee brace in flexion (60°) for five consecutive days.
Device: Knee immobilization brace (60°) for 5 days
Unilateral knee immobilization at 0° flexion for 5 days using a brace; post-immobilization metabolic testing with tracer infusions and biopsies
Unilateral knee immobilization at 60° flexion for 5 days using a brace; post-immobilization metabolic testing with tracer infusions and biopsies
Muscle protein net balance (MPNB)
Muscle protein net balance expressed as %/h and calculated as the difference between muscle protein synthesis (MPS; fractional synthesis rate, FSR) and muscle protein breakdown (MPB; fractional breakdown rate, FBR), measured in skeletal muscle following 5 days of unilateral knee immobilization
Time frame: Baseline to 3 hours after tracer infusion
Thigh muscle volume
Thigh muscle volume, including muscle length and cross-sectional area, measured via Magnetic Resonance Imaging (MRI)
Time frame: Baseline and after 5 days of immobilization
Muscle strength
Maximal voluntary muscle strength measured as peak torque using isokinetic dynamometry
Time frame: Baseline and after 5 days of immobilization
Muscle fatigue
Muscle fatigue assessed as decline in force during repeated contractions measured using isokinetic dynamometry
Time frame: Baseline and after 5 days of immobilization
Intramuscular fat content
Intramuscular lipid content measured using 1H-magnetic resonance spectroscopy (1H-MRS)
Time frame: Baseline and after 5 days of immobilization
Muscle metabolite concentrations
Carnosine and acetylcarnitine concentrations in skeletal muscle measured using 1H-magnetic resonance spectroscopy (1H-MRS)
Time frame: Baseline and after 5 days of immobilization
Mitochondrial respiration
Mitochondrial respiration measured as oxygen consumption in permeabilized muscle fibres using high-resolution respirometry
Time frame: Baseline and after 5 days of immobilization
Mitochondrial reactive oxygen species production
Mitochondrial reactive oxygen species (ROS) production measured using fluorescence-based detection in permeabilized muscle fibres
Time frame: Baseline and after 5 days of immobilization
Mitochondrial calcium retention capacity
Calcium retention capacity measured in permeabilized muscle fibres using fluorescence-based assays
Time frame: Baseline and after 5 days of immobilization
Muscle gene expression related to atrophy
Expression of genes involved in muscle atrophy measured in skeletal muscle biopsy samples using molecular analysis techniques (e.g. qPCR or RNA sequencing)
Time frame: Baseline and after 5 days of immobilization
Muscle protein markers of atrophy
Protein expression of markers related to muscle protein synthesis and breakdown measured in skeletal muscle biopsy samples
Time frame: Baseline and after 5 days of immobilization
Plasma amino acid concentration
Plasma concentration of amino acids measured in venous blood samples
Time frame: Baseline to 3 hours after tracer infusion
Serum insulin concentration
Serum insulin concentration measured in venous blood samples
Time frame: Baseline and up to 3 hours after tracer infusion
Body weight
Body weight measured in kilograms
Time frame: Baseline (pre-intervention)
Height
Height measured in meters
Time frame: Baseline (pre-intervention)
Body mass index (BMI)
Body mass index calculated as kg/m²
Time frame: Baseline (pre-intervention)
Body composition
Fat mass and lean mass measured using DXA
Time frame: Baseline (pre-intervention)
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Wageningen University