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Effect of Knee Position on Muscle Loss During Leg Immobilization

1. Juli 2026 aktualisiert von: 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.

Studienübersicht

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Geschätzt)

30

Phase

  • Unzutreffend

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

  • Erwachsene

Akzeptiert gesunde Freiwillige

Ja

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Grundlegende Wissenschaft
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Aktiver Komparator: 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
Experimental: 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

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Muscle protein net balance (MPNB)
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Thigh muscle volume
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Andere Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Height
Zeitfenster: Baseline (pre-intervention)
Height measured in meters
Baseline (pre-intervention)
Plasma amino acid concentration
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: Baseline (pre-intervention)
Body weight measured in kilograms
Baseline (pre-intervention)
Body mass index (BMI)
Zeitfenster: Baseline (pre-intervention)
Body mass index calculated as kg/m²
Baseline (pre-intervention)
Body composition
Zeitfenster: Baseline (pre-intervention)
Fat mass and lean mass measured using DXA
Baseline (pre-intervention)

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

1. August 2026

Primärer Abschluss (Geschätzt)

1. März 2028

Studienabschluss (Geschätzt)

1. Juni 2028

Studienanmeldedaten

Zuerst eingereicht

17. April 2026

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

1. Juli 2026

Zuerst gepostet (Tatsächlich)

8. Juli 2026

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

8. Juli 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

1. Juli 2026

Zuletzt verifiziert

1. Juli 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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