Effect of Knee Position on Muscle Loss During Leg Immobilization

July 1, 2026 updated by: 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Neutral Knee Position
Participants in this group wear a knee brace in full extension (0°) for five consecutive days.
Device: Knee immobilization brace (0°) for 5 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.
Device: Knee immobilization brace (60°) for 5 days
Unilateral knee immobilization at 60° flexion for 5 days using a brace; post-immobilization metabolic testing with tracer infusions and biopsies

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Muscle protein net balance (MPNB)
Time Frame: 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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Thigh muscle volume
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Height
Time Frame: Baseline (pre-intervention)
Height measured in meters
Baseline (pre-intervention)
Plasma amino acid concentration
Time Frame: 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
Time Frame: 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
Time Frame: Baseline (pre-intervention)
Body weight measured in kilograms
Baseline (pre-intervention)
Body mass index (BMI)
Time Frame: Baseline (pre-intervention)
Body mass index calculated as kg/m²
Baseline (pre-intervention)
Body composition
Time Frame: Baseline (pre-intervention)
Fat mass and lean mass measured using DXA
Baseline (pre-intervention)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Wageningen University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ZonMw: The Netherlands Organisation for Health Research and Development

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 17, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 8, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 8, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL010759

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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