Effect of Knee Position on Muscle Loss During Leg Immobilization
keskiviikko 1. heinäkuuta 2026 päivittänyt: Marlou Dirks, Wageningen University
A Novel Angle: Manipulating Knee Position to Understand Muscle Deterioration During Leg Immobilization
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.
Tutkimuksen yleiskatsaus
Tila
Ei vielä rekrytointia
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Interventio
Ilmoittautuminen (Arvioitu)
30
Vaihe
- Ei sovellettavissa
Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
Hyväksyy terveitä vapaaehtoisia
Joo
Kuvaus
Inclusion Criteria:
- Healthy males and females
- Aged from 18-40 years at the time of signing informed consent
- 18.5 < BMI < 30 kg·m-2
- Must be willing and able to communicate and participate in the whole study
Exclusion Criteria:
- Smoking
- Diabetes (Type 1, Type 2, or genetic form of diabetes)
- Any diagnosed cardiovascular (heart) disease or high blood pressure (≥140 mmHg systolic and/or ≥90 mmHg diastolic)
- Chronic use of any prescribed or over the counter pharmaceuticals that may modulate muscle protein metabolism (excluding oral contraceptives and contraceptive devices).
- A personal or family history of thrombosis, epilepsy, seizures or schizophrenia.
- Prone to keloid forming (i.e. hyperplastic growth of scars).
- Any known disorders in muscle metabolism
- Regular use of dietary protein and/or amino acid supplements (>3 times per week)
- Currently involved in a structured progressive resistance training programme (>3 times per week)
- Known allergy to lidocaine
- Known severe kidney problems
- Allergy to one or multiple amino acids
- Recent (within the last 6 months) or current musculoskeletal injury (e.g. leg fracture)
- Having received or ingested a stable isotope tracer containing 15N in the past
- Contra-indications for MRI such as incompatible metal objects in the body and claustrophobia.
- Currently taking part in other scientific research
- Pregnant or breastfeeding
- Unable to give consent
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Perustiede
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
|---|---|
|
Active Comparator: Neutral Knee Position
Participants in this group wear a knee brace in full extension (0°) for five consecutive days.
|
Unilateral knee immobilization at 0° flexion for 5 days using a brace; post-immobilization metabolic testing with tracer infusions and biopsies
|
|
Kokeellinen: Flexed Knee Position
Participants in this group wear a knee brace in flexion (60°) for five consecutive days.
|
Unilateral knee immobilization at 60° flexion for 5 days using a brace; post-immobilization metabolic testing with tracer infusions and biopsies
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Muscle protein net balance (MPNB)
Aikaikkuna: Baseline to 3 hours after tracer infusion
|
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
|
Baseline to 3 hours after tracer infusion
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Thigh muscle volume
Aikaikkuna: Baseline and after 5 days of immobilization
|
Thigh muscle volume, including muscle length and cross-sectional area, measured via Magnetic Resonance Imaging (MRI)
|
Baseline and after 5 days of immobilization
|
|
Muscle strength
Aikaikkuna: Baseline and after 5 days of immobilization
|
Maximal voluntary muscle strength measured as peak torque using isokinetic dynamometry
|
Baseline and after 5 days of immobilization
|
|
Muscle fatigue
Aikaikkuna: Baseline and after 5 days of immobilization
|
Muscle fatigue assessed as decline in force during repeated contractions measured using isokinetic dynamometry
|
Baseline and after 5 days of immobilization
|
|
Intramuscular fat content
Aikaikkuna: Baseline and after 5 days of immobilization
|
Intramuscular lipid content measured using 1H-magnetic resonance spectroscopy (1H-MRS)
|
Baseline and after 5 days of immobilization
|
|
Muscle metabolite concentrations
Aikaikkuna: Baseline and after 5 days of immobilization
|
Carnosine and acetylcarnitine concentrations in skeletal muscle measured using 1H-magnetic resonance spectroscopy (1H-MRS)
|
Baseline and after 5 days of immobilization
|
|
Mitochondrial respiration
Aikaikkuna: Baseline and after 5 days of immobilization
|
Mitochondrial respiration measured as oxygen consumption in permeabilized muscle fibres using high-resolution respirometry
|
Baseline and after 5 days of immobilization
|
|
Mitochondrial reactive oxygen species production
Aikaikkuna: Baseline and after 5 days of immobilization
|
Mitochondrial reactive oxygen species (ROS) production measured using fluorescence-based detection in permeabilized muscle fibres
|
Baseline and after 5 days of immobilization
|
|
Mitochondrial calcium retention capacity
Aikaikkuna: Baseline and after 5 days of immobilization
|
Calcium retention capacity measured in permeabilized muscle fibres using fluorescence-based assays
|
Baseline and after 5 days of immobilization
|
|
Muscle gene expression related to atrophy
Aikaikkuna: Baseline and after 5 days of immobilization
|
Expression of genes involved in muscle atrophy measured in skeletal muscle biopsy samples using molecular analysis techniques (e.g.
qPCR or RNA sequencing)
|
Baseline and after 5 days of immobilization
|
|
Muscle protein markers of atrophy
Aikaikkuna: Baseline and after 5 days of immobilization
|
Protein expression of markers related to muscle protein synthesis and breakdown measured in skeletal muscle biopsy samples
|
Baseline and after 5 days of immobilization
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Height
Aikaikkuna: Baseline (pre-intervention)
|
Height measured in meters
|
Baseline (pre-intervention)
|
|
Plasma amino acid concentration
Aikaikkuna: Baseline to 3 hours after tracer infusion
|
Plasma concentration of amino acids measured in venous blood samples
|
Baseline to 3 hours after tracer infusion
|
|
Serum insulin concentration
Aikaikkuna: Baseline and up to 3 hours after tracer infusion
|
Serum insulin concentration measured in venous blood samples
|
Baseline and up to 3 hours after tracer infusion
|
|
Body weight
Aikaikkuna: Baseline (pre-intervention)
|
Body weight measured in kilograms
|
Baseline (pre-intervention)
|
|
Body mass index (BMI)
Aikaikkuna: Baseline (pre-intervention)
|
Body mass index calculated as kg/m²
|
Baseline (pre-intervention)
|
|
Body composition
Aikaikkuna: Baseline (pre-intervention)
|
Fat mass and lean mass measured using DXA
|
Baseline (pre-intervention)
|
Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Yhteistyökumppanit
Julkaisuja ja hyödyllisiä linkkejä
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Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
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Kliiniset tutkimukset Lihasatrofia
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Sheffield Children's NHS Foundation TrustEi vielä rekrytointiaSMA - Spinal Muscular AtrophyYhdistynyt kuningaskunta
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Teachers College, Columbia UniversityAktiivinen, ei rekrytointi
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Tokyo UniversityNobelpharmaRekrytointiMultiple System Atrophy (MSA)Japani
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Johannes Gutenberg University MainzDentsply Sirona ImplantsTuntematonDistaalisen alaleuan kalteva atrofia | Socket Like Atrophy of the Aesthetic ZoneSaksa
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MODAG GmbHInstitute for Neurodegenerative Disorders; XingImaging, LLCRekrytointiParkinsonin tauti | Terve aikuinen | Multiple System Atrophy (MSA)Yhdysvallat
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Synusight Biotech (Shanghai) Co., Ltd.RekrytointiParkinsonin tauti (PD) | Multiple System Atrophy (MSA)Kiina
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Novartis Gene TherapiesValmisGeeniterapia | SMA - Spinal Muscular AtrophyYhdysvallat
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Biocells MedicalEi vielä rekrytointiaMSA - Multiple System Atrophy | MSAPuola
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Fondazione I.R.C.C.S. Istituto Neurologico Carlo...Aktiivinen, ei rekrytointi
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University of Texas Southwestern Medical CenterRekrytointi