Effects of immobilization and retraining on muscle function in young and older adults

ISRCTN	ISRCTN13300028
DOI	https://doi.org/10.1186/ISRCTN13300028
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	Nil known
Sponsor	University of Basel
Funder	Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Submission date: 24/03/2025
Registration date: 25/03/2025
Last edited: 05/11/2025

Recruitment status: Not yet recruiting
Overall study status: Ongoing
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Aging and periods of immobilization due to injury or illness can lead to a decline in muscle strength, balance, and mobility, particularly in older adults. Women and older individuals may experience more severe declines and slower recovery after immobilization, but research on these effects is limited. This study aims to investigate how young and older men and women respond to a period of leg immobilization and subsequent retraining, helping to improve rehabilitation strategies for different age and sex groups.

Who can participate?
Healthy young adults (18-30 years) and older adults (60-70 years) who live independently and can attend training sessions.

What does the study involve?
Participants will undergo 10 days of unilateral lower limb suspension using a sling, followed by 3 weeks of supervised re-training (i.e. resistance training). The study will assess changes in muscular strength, balance, gait, and neuromuscular activation before and after immobilization and retraining. Testing will include strength measurements, gait and balance tests, MRI scans, ultrasound assessments, anthropometry, blood pressure and muscular activation.

What are the possible benefits and risks of participating?
Participants will gain insights into their physical performance and may improve their strength and motor functions through the retraining phase. Potential risks include muscle weakness and discomfort due to immobilization, which will be closely monitored. Preventative measures, such as an extensive medical check prior to the inclusion of volunteers, will be in place to minimize health risks.

Where is the study run from?
The training and testing will be conducted at the Department of Sport, Exercise and Health, University of Basel, Switzerland. MRI scans will take place at the research scanner of University Hospital Basel.

When is the study starting and how long is it expected to run?
The study is expected to begin in January 2026 and will run for approximately 3 years, including recruitment, intervention, and data analysis.

Who is funding the study?
The study is funded by the Swiss National Science Foundation.

Who is the main contact?
Martin Keller, martin.keller@unibas.ch

Contact information

Mr Martin Keller
Public, Scientific, Principal investigator

Grosse Allee 6
Basel
4052
Switzerland

ORCID ID	0000-0002-8375-3213
Phone	+41 61 207 6077
Email	martin.keller@unibas.ch

Study information

Primary study design	Interventional
Study design	Parallel group intervention study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	frAGILE: does function follow form in young and old adults in immobilization and retraining?
Study acronym	frAGILE
Study objectives	Current Study objectives as of 05/11/2025: The aim of the study is to investigate the effects of a period of immobilization followed by re-training on neuromuscular function, with a focus on sex- and age-specific effects. Age-related effects: Older adults will experience greater declines in neuromuscular function after immobilization compared to young adults, with incomplete recovery after retraining. Sex-related effects: Women will show more pronounced declines in neuromuscular function after immobilization period compared to men. _____ Previous Study objectives: Age-related effects: Older adults will experience greater declines in neuromuscular function after immobilization compared to young adults, with incomplete recovery after retraining. Sex-related effects: Women will show more pronounced declines in neuromuscular function after immobilization period compared to men.
Ethics approval(s)	Not yet submitted, Ethikkommission Nordwest- und Zentralschweiz (Hebelstrasse 53, Basel, 4056, Switzerland; +41 (0)61 268 13 50; eknz@bs.ch)
Health condition(s) or problem(s) studied	Investigating the effects of unilateral lower limb immobilization and re-training in healthy young and older men and women.
Intervention	Current interventions as of 05/11/2025: Participants will undergo 10 days of unilateral lower limb suspension using a sling to restrict movements and simulate muscle disuse. During this period, participants will be provided with crutches and instructed to avoid using the immobilized leg. Compliance will be monitored using accelerometers and activity logs. Following immobilization, participants will complete 3 weeks of supervised retraining, consisting of resistance exercises targeting the immobilized leg. Training sessions will take place at the University of Basel and will focus on strength and neuromuscular activation. The training intensity will be progressively adapted based on individual performance assessments. Assessments of muscle strength, balance, gait, neuromuscular activation, and muscle structure will be conducted before and after immobilization, as well as throughout the retraining phase. _____ Previous interventions: Participants will undergo 10 days of unilateral lower limb immobilization using a cast to restrict movements and simulate muscle disuse. During this period, participants will be provided with crutches and instructed to avoid using the immobilized leg. Compliance will be monitored using accelerometers and activity logs. Following immobilization, participants will complete 3 weeks of supervised retraining, consisting of resistance exercises targeting the immobilized leg. Training sessions will take place at the University of Basel and will focus on strength and neuromuscular activation. The training intensity will be progressively adapted based on individual performance assessments. Assessments of muscle strength, balance, gait, neuromuscular activation, and muscle structure will be conducted before and after immobilization, as well as throughout the retraining phase.
Intervention type	Other
Primary outcome measure(s)	Primary outcomes will be assessed before and after the disuse period as well as after the retraining period. Furthermore, the primary outcomes will be assessed in a mid-training test. 1. Knee extensor and flexor strength – Measured using isometric dynamometry to assess maximum voluntary contractions but also the rate of force development of knee extensors and knee flexors. 2. Balance performance – Evaluated using single-leg stance and tandem stance on a force platform. 3. Gait analysis– Gait analyses will be done using an optoelectric walkway to assess gait parameters such walking speed, stride length, or stride variability.
Key secondary outcome measure(s)	Secondary outcomes will be assessed before and after the disuse period as well as after the retraining period. 1. Voluntary Activation of knee extensors – The twitch-interpolation technique will be used to assess the level of voluntary activation of knee extensor muscles. 2. Muscle architecture and contractility – Muscle contractility during voluntary contractions will be assessed using dynamic ultrasound. Different parameters of muscle architecture and contractility such as fascicle length, pennation angle, fascicle shortening velocity, amount of shortening and changes in pennation angle will be assessed for the Vastus lateralis muscle during maximum voluntary contractions. 3. Muscular activation – High-density electromyography (HD-EMG) is a non-invasive technique to measure the electrical activity produced by skeletal muscles. HD-EMG signals will be recorded from the musculus vastus lateralis during contractions of different contraction intensities. A grid of electrodes will be used to assess central and peripheral properties of motor units. 4. Tendon stiffness – The stiffness of the patellar tendon will be assessed using dynamic ultrasonography. An ultrasound probe will therefore be fixated on the patellar tendon during a ramped isometric knee extension contraction. 5. Muscle and tendon volume and muscle strain – A magnetic resonance imaging (MRI) scanner will be used to assess muscle and tendon parameters such as muscle and tendon volume. Additionally, dynamic MRI to determine muscle deformation and strain will be performed in combination with neuromuscular electrical stimulation. 6. Anthropometry – Whole body as well as lower limb skeletal muscle mass, fat mass, lean mass, bone mineral density and bone mineral content will be obtained using dual-energy x-ray absorptiometry. 7. Blood pressure – Brachial blood pressure will be measured in a supine position after 10 min of rest using an automatic blood pressure monitor. 8. Accelerometry – Participants will be asked to wear accelerometers before, during and after the intervention period. Data from accelerometers will be used to monitor the total time spent passively and actively 9. Questionnaires and Diaries – Diaries and questionnaires will be used to record (inter alia) protein and caloric intake but also physical activity.
Completion date	31/12/2028

Eligibility

Participant type(s)	Healthy volunteer
Age group	Mixed
Lower age limit	18 Years
Upper age limit	70 Years
Sex	All
Target sample size at registration	40
Key inclusion criteria	Current key inclusion criteria as of 05/11/2025: 1. Healthy men and women aged 18 to 30 years (young) as well as older adults (60-70 years) - active persons performing 1-3 active sessions per week 2. Willing and physically able to undergo the study demands (immobilization period and retraining exercises) 3. Daily tasks should not require them to be physically active during the immobilization period 4. Be able to travel to the facilities of the Department of Sports, Exercise and Health, University of Basel for the measurement sessions and three times per week to complete the retraining period 5. Be able to travel 5 times to the Department of Sports, Exercise and Health and to the University Hospital Basel for the measurement sessions 6. All participants will receive a medical examination and need medical clearance for participation 7. Signed informed consent _____ Previous key inclusion criteria: 1. Age Groups: Young adults (18-35 years) and older adults (>65 years). 2. Health Status: Primarily healthy individuals living independently in the community. 3. Physical Ability: Participants must be physically capable of undergoing the study demands, including immobilization and retraining. 4. Daily Activity Requirements: Daily tasks should not require participants to be physically active during the immobilization period. 5. Travel Availability: Participants must be able to travel to the Department of Sports, Exercise, and Health at the University of Basel for the retraining phase. 6. Medical Clearance: All participants must undergo a medical examination and receive medical clearance to participate.
Key exclusion criteria	Current key exclusion criteria as of 05/11/2025: 1. History of cardiovascular, pulmonary or chronic inflammatory disease 2. Personal or family history of blood clots 3. Orthopaedic problems or surgery (within the last 6 months) 4. Body mass index >35 kg/m2 5. Pregnancy 6. History of osteoporosis or a recent (past 6 months) low‐trauma fracture 7. Use of assistive walking device within the previous year 8. Expecting to travel abroad throughout the intervention 9. Participants who do not agree to the collected data being made available in coded form (open science) 10. History of cancer within the past 5 years 11. Current use of oral contraceptives with esrtogen or oestrogenic hormone therapy 12. Usual contraindications to MRI as defined in the clinical practice _____ Previous key exclusion criteria: 1. Medical Conditions: 1.1. History of cardiovascular, pulmonary, or chronic inflammatory diseases. 1.2. Personal or family history of blood clots. 1.3. Allergy to heparin (used for anticoagulation during immobilization). 2. Orthopedic Issues: 2.1. Recent orthopedic surgery (within the last six months). 2.2. Existing orthopedic problems that could interfere with participation. 3. Body Composition: 3.1. Body mass index (BMI) > 30 kg/m². 4. Bone Health: 4.1. History of osteoporosis. 4.2. Recent (past six months) low-trauma fracture. 5. Mobility and Functional Restrictions: 5.1. Use of assistive walking devices within the previous year. 5.2. Expectation of travel during the intervention period. 6. Pregnancy: 6.1. Pregnant individuals will be excluded.
Date of first enrolment	01/01/2026
Date of final enrolment	31/12/2027

Locations

Countries of recruitment

Switzerland

Study participating centre

University of Basel; Department of Sport, Exercise and Health

Grosse Allee 6
Basel
4052
Switzerland

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later stage.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

05/11/2025: The following changes were made to the trial record:
1. The Study objectives were changed.
2. The Study design was changed from "Interventional non randomized" to "Parallel group intervention study".
3. The overall start date was changed from 01/04/2025 to 01/07/2025.
4. The interventions were changed.
5. The key inclusion criteria were changed.
6. The key exclusion criteria were changed.
7. The date of first enrolment was changed from 01/11/2025 to 01/01/2026.
8. The date of final enrolment was changed from 30/11/2027 to 31/12/2027.
9. The plain English summary was updated to reflect these changes.
24/03/2025: Trial's existence confirmed by Swiss National Science Foundation (SNSF).