Effects of immobilization and retraining on muscle function in young and older adults
| ISRCTN | ISRCTN13300028 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13300028 |
- Submission date
- 24/03/2025
- Registration date
- 25/03/2025
- Last edited
- 24/03/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Musculoskeletal Diseases
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 (18-35 years) and older adults (65 years and older) who live independently and can attend training sessions.
What does the study involve?
Participants will undergo 10 days of unilateral lower limb immobilization using a cast, 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 November 2025 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
Public, Scientific, Principal Investigator
Grosse Allee 6
Basel
4052
Switzerland
 ORCID ID |
0000-0002-8375-3213 |
|---|---|
| Phone | +41 61 207 6077 |
| martin.keller@unibas.ch |
Study information
| Study design | Interventional non randomized |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Home, Laboratory |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | frAGILE: does function follow form in young and old adults in immobilization and retraining? |
| Study acronym | frAGILE |
| 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 | 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 | 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. |
| Secondary outcome measures | 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. |
| Overall study start date | 01/04/2025 |
| Completion date | 31/12/2028 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 10 per group (young women, young men, older women, older men) |
| 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 | 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 | 01/11/2025 |
| Date of final enrolment | 30/11/2027 |
Locations
Countries of recruitment
- Switzerland
Study participating centre
Basel
4052
Switzerland
Sponsor information
University/education
Department for Sport, Exercise and Health
Grosse Allee 6
Basel
4052
Switzerland
| Phone | +41 61 207 6077 |
|---|---|
| fragile-dsbg@unibas.ch | |
| Website | https://www.unibas.ch |
"ROR" |
https://ror.org/02s6k3f65 |
Funders
Funder type
Government
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Schweizerischer Nationalfonds, Swiss National Science Foundation, Fonds National Suisse de la Recherche Scientifique, Fondo Nazionale Svizzero per la Ricerca Scientifica, Fonds National Suisse, Fondo Nazionale Svizzero, Schweizerische Nationalfonds, SNF, SNSF, FNS
- Location
- Switzerland
Results and Publications
| Intention to publish date | 31/08/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later stage. |
Editorial Notes
24/03/2025: Trial's existence confirmed by Swiss National Science Foundation (SNSF).
