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Muscle AtrophyNCT07690150

Effect of Knee Position on Muscle Loss During Leg Immobilization

A study testing Knee immobilization brace (0°) for 5 days and Knee immobilization brace (60°) for 5 days in people with Muscle Atrophy and Disuse Atrophy, run by Wageningen University.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for
Muscle Atrophy, Disuse Atrophy, Immobilization
What is being tested?
Knee immobilization brace (0°) for 5 days and Knee immobilization brace (60°) for 5 days
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
No sites listed yet
Study dates
1 Aug 2026to 1 Jun 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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).
Show all 18Show fewer
  • 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

About this study

Official title: 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.

Read the 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.

Being tested
Knee immobilization brace (0°) for 5 days, Knee immobilization brace (60°) for 5 days
Keywords
Quadriceps, Knee Brace, Muscle Protein Breakdown, Dynamometry, Stable Isotope Tracers, MRI
Medical subject headings
Muscular Atrophy, Muscular Disorders, Atrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Knee immobilization brace (0°) for 5 daysDevice

    Unilateral knee immobilization at 0° flexion for 5 days using a brace; post-immobilization metabolic testing with tracer infusions and biopsies

  • Knee immobilization brace (60°) for 5 daysDevice

    Unilateral knee immobilization at 60° flexion for 5 days using a brace; post-immobilization metabolic testing with tracer infusions and biopsies

Study groups in NCT07690150
Study groupRoleWhat they receive
Neutral Knee PositionActive comparatorParticipants in this group wear a knee brace in full extension (0°) for five consecutive days.
Receives: Device: Knee immobilization brace (0°) for 5 days
Flexed Knee PositionExperimentalParticipants in this group wear a knee brace in flexion (60°) for five consecutive days.
Receives: Device: Knee immobilization brace (60°) for 5 days

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline to 3 hours after tracer infusion

Secondary outcomes (10)
  1. Thigh muscle volume

    Thigh muscle volume, including muscle length and cross-sectional area, measured via Magnetic Resonance Imaging (MRI)

    Measured: Baseline and after 5 days of immobilization

  2. Muscle strength

    Maximal voluntary muscle strength measured as peak torque using isokinetic dynamometry

    Measured: Baseline and after 5 days of immobilization

  3. Muscle fatigue

    Muscle fatigue assessed as decline in force during repeated contractions measured using isokinetic dynamometry

    Measured: Baseline and after 5 days of immobilization

  4. Intramuscular fat content

    Intramuscular lipid content measured using 1H-magnetic resonance spectroscopy (1H-MRS)

    Measured: Baseline and after 5 days of immobilization

  5. Muscle metabolite concentrations

    Carnosine and acetylcarnitine concentrations in skeletal muscle measured using 1H-magnetic resonance spectroscopy (1H-MRS)

    Measured: Baseline and after 5 days of immobilization

  6. Mitochondrial respiration

    Mitochondrial respiration measured as oxygen consumption in permeabilized muscle fibres using high-resolution respirometry

    Measured: Baseline and after 5 days of immobilization

  7. Mitochondrial reactive oxygen species production

    Mitochondrial reactive oxygen species (ROS) production measured using fluorescence-based detection in permeabilized muscle fibres

    Measured: Baseline and after 5 days of immobilization

  8. Mitochondrial calcium retention capacity

    Calcium retention capacity measured in permeabilized muscle fibres using fluorescence-based assays

    Measured: Baseline and after 5 days of immobilization

  9. 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)

    Measured: Baseline and after 5 days of immobilization

  10. Muscle protein markers of atrophy

    Protein expression of markers related to muscle protein synthesis and breakdown measured in skeletal muscle biopsy samples

    Measured: Baseline and after 5 days of immobilization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2026
  2. Study start1 Aug 2026 (estimated)
  3. Primary completion1 Mar 2028 (estimated)
  4. Study completion1 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants are randomized into two parallel groups: one group wears a knee brace in full extension (0°), and the other in flexion (60°) for five consecutive days. The contralateral leg serves as an internal control. Randomization is stratified by sex and performed in permuted blocks to ensure balanced allocation. There is no masking because the knee position is visible. Both groups undergo identical procedures before and after immobilization, including imaging and metabolic assessments.
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07690150
Sponsor's protocol ID
NL010759
Status last verified
Jul 2026
First submitted
17 Apr 2026
Last updated
8 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • World Medical Association Inc. Declaration of Helsinki. Ethical principles for medical research involving human subjects. J Indian Med Assoc. 2009 Jun;107(6):403-5. No abstract available.

    PubMed 19886379
  • Wolfe, R.R.C., D.L., Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis. 2004.

  • Gouspillou G, Sgarioto N, Kapchinsky S, Purves-Smith F, Norris B, Pion CH, Barbat-Artigas S, Lemieux F, Taivassalo T, Morais JA, Aubertin-Leheudre M, Hepple RT. Increased sensitivity to mitochondrial permeability transition and myonuclear translocation of endonuclease G in atrophied muscle of physically active older humans. FASEB J. 2014 Apr;28(4):1621-33. doi: 10.1096/fj.13-242750. Epub 2013 Dec 26.

    PubMed 24371120
  • Holloway GP, Holwerda AM, Miotto PM, Dirks ML, Verdijk LB, van Loon LJC. Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle. Cell Rep. 2018 Mar 13;22(11):2837-2848. doi: 10.1016/j.celrep.2018.02.069.

    PubMed 29539414
  • Pinckaers PJ, Petrick HL, Horstman AM, Moreno-Asso A, De Marchi U, Hendriks FK, Kuin LM, Fuchs CJ, Grathwohl D, Verdijk LB, Zorenc AH, Senden JM, Migliavacca E, Metairon S, Poquet L, Morin-Rivron D, Karagounis LG, Holloway GP, Feige JN, van Loon LJ. Oleuropein Supplementation Increases Resting Skeletal Muscle Fractional Pyruvate Dehydrogenase Activity but Does Not Influence Whole-Body Metabolism: A Randomized, Double-Blind, and Placebo-Controlled Trial in Healthy, Older Males. J Nutr. 2025 May;155(5):1373-1386. doi: 10.1016/j.tjnut.2025.02.015. Epub 2025 Feb 22.

    PubMed 39993475
  • Pavis GF, Abdelrahman DR, Murton AJ, Wall BT, Stephens FB, Dirks ML. Nasogastric bolus administration of a protein-rich drink augments insulinaemia and aminoacidaemia but not whole-body protein turnover or muscle protein synthesis versus oral administration. Clin Sci (Lond). 2024 Jan 10;138(1):43-60. doi: 10.1042/CS20231126.

    PubMed 38112515
  • Dirks ML, Wall BT, Kramer IF, Zorenc AH, Goessens JP, Gijsen AP, van Loon LJ. A single session of neuromuscular electrical stimulation does not augment postprandial muscle protein accretion. Am J Physiol Endocrinol Metab. 2016 Jul 1;311(1):E278-85. doi: 10.1152/ajpendo.00085.2016. Epub 2016 Jun 7.

    PubMed 27279248
  • West S, Monteyne AJ, Whelehan G, Abdelrahman DR, Murton AJ, Finnigan TJA, Blackwell JR, Stephens FB, Wall BT. Mycoprotein ingestion within or without its wholefood matrix results in equivalent stimulation of myofibrillar protein synthesis rates in resting and exercised muscle of young men. Br J Nutr. 2023 Jul 14;130(1):20-32. doi: 10.1017/S0007114522003087. Epub 2022 Sep 29.

    PubMed 36172885
  • Monteyne AJ, Coelho MOC, Porter C, Abdelrahman DR, Jameson TSO, Finnigan TJA, Stephens FB, Dirks ML, Wall BT. Branched-Chain Amino Acid Fortification Does Not Restore Muscle Protein Synthesis Rates following Ingestion of Lower- Compared with Higher-Dose Mycoprotein. J Nutr. 2020 Nov 19;150(11):2931-2941. doi: 10.1093/jn/nxaa251.

    PubMed 32886108
  • Dirks ML, Tieland M, Verdijk LB, Losen M, Nilwik R, Mensink M, de Groot LCPGM, van Loon LJC. Protein Supplementation Augments Muscle Fiber Hypertrophy but Does Not Modulate Satellite Cell Content During Prolonged Resistance-Type Exercise Training in Frail Elderly. J Am Med Dir Assoc. 2017 Jul 1;18(7):608-615. doi: 10.1016/j.jamda.2017.02.006. Epub 2017 Apr 1.

    PubMed 28377156
  • Dirks ML, Wall BT, van de Valk B, Holloway TM, Holloway GP, Chabowski A, Goossens GH, van Loon LJ. One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation. Diabetes. 2016 Oct;65(10):2862-75. doi: 10.2337/db15-1661. Epub 2016 Jun 29.

    PubMed 27358494
  • Dirks ML, Hansen D, Van Assche A, Dendale P, Van Loon LJ. Neuromuscular electrical stimulation prevents muscle wasting in critically ill comatose patients. Clin Sci (Lond). 2015 Mar;128(6):357-65. doi: 10.1042/CS20140447.

    PubMed 25296344
  • Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975 Nov;35(7):609-16. No abstract available.

    PubMed 1108172
  • Hortobagyi T, Dempsey L, Fraser D, Zheng D, Hamilton G, Lambert J, Dohm L. Changes in muscle strength, muscle fibre size and myofibrillar gene expression after immobilization and retraining in humans. J Physiol. 2000 Apr 1;524 Pt 1(Pt 1):293-304. doi: 10.1111/j.1469-7793.2000.00293.x.

    PubMed 10747199
  • Berg HE, Dudley GA, Haggmark T, Ohlsen H, Tesch PA; New Collective Author. Effects of lower limb unloading on skeletal muscle mass and function in humans. J Appl Physiol (1985). 1991 Apr;70(4):1882-5. doi: 10.1152/jappl.1991.70.4.1882.

    PubMed 2055867

Questions about this trial

What is this clinical trial studying?

A study testing Knee immobilization brace (0°) for 5 days and Knee immobilization brace (60°) for 5 days in people with Muscle Atrophy and Disuse Atrophy, run by Wageningen University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Muscle protein net balance (MPNB) (time frame: Baseline to 3 hours after tracer infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07690150, which also lists 48 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.

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