Muscular AtrophyiMOBNCT04199923
Mechanisms of Disuse Atrophy in Human Skeletal Muscle (iMOB)
A study testing Single leg immobilisation in people with Muscular Atrophy and Immobility Syndrome, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
Loss of muscle can be caused by a variety of stimuli and results in reduced mobility and strength and also impacts whole body health. Whilst it is known that muscles waste the process by which this occurs is not well understood. Read more about this study
- Who is it for?
- Ages 18 to 80 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Muscular Atrophy, Immobility Syndrome
- What is being tested?
- Single leg immobilisation
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2019to 1 Oct 2026
- 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 80 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Group 1 and 2: Male, Age 18-40, BMI 18-35
- Group 3: Male, Age 65-80, BMI 18-35
Who cannot join
- BMI > 35 / <18
- Female
- Personal or Family History of Venous Thromboembolism
- Significant medical comorbidities
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Graduate Entry Medical School
Derby, Derbyshire, DE22 3DT
About this study
Official title: Harnessing Muscle-specific Atrophy Susceptibility to Disentangle the Mechanisms of Disuse Atrophy in Human Skeletal Muscle Atrophy (iMOB)
Loss of muscle can be caused by a variety of stimuli and results in reduced mobility and strength and also impacts whole body health. Whilst it is known that muscles waste the process by which this occurs is not well understood. Furthermore, whilst some muscles waste quickly others seem resistant to the effects of disuse.
This study aims to evaluate how quickly changes in muscles start to occur, and investigate the processes which underlie muscle atrophy. By studying muscles which waste quickly and those which are resistant to atrophy this study aims to identify the different processes which lead to muscle loss. This study will also evaluate the differences in muscle changes between young and old people.
Read the detailed description
Skeletal muscles host ~40% of all protein in the body. Muscles are not only crucial for locomotion but also represent the body's largest metabolically active tissue, glucose disposal site and fuel reservoir for other organs in pathological conditions (i.e., supply of amino acids to the liver for gluconeogenesis). Muscle atrophy is characterized by a reduction in cross sectional area (CSA) and length and occurs in many common illnesses (e.g. cancers (1), renal/heart failure, sepsis, genetic diseases, neurodegenerative disorders etc). It is also prevalent in situations of reduced neural input such as leg casting after fractures (2), bed-rest, spinal cord injury (3), space flight and chronic physical inactivity. Atrophy results in a loss of muscle power and strength (which is related to increased morbidity and mortality (4)) and reduced capacities for whole-body glucose storage and metabolism which causes insulin resistance. Strategies to oppose atrophy are limited but include mechanical loading (5) and the synergistic anabolic effects of nutrients. Although muscle atrophy is of great clinical importance, relatively little mechanistic research has been done in humans. Thus, the aim of this study is to assess the link between the variation in muscle physiological responses to disuse atrophy with variation in protein turnover and molecular-networks. This will not only provide new hypotheses for physiological regulation of human muscle and generate 'intervention targets' derived from clinically relevant human studies, it will also improve understanding of whether the response to disuse is altered with age and determine if mechanistic differences in atrophy resistant and atrophy sensitive muscles might explain inter-muscular variation in susceptibility to atrophy.
This study aims to define the molecular and metabolic mechanisms causing disuse atrophy in both young and older individuals and explore how and why some muscles are protected against it. The study will also assess temporal aspects of disuse atrophy (in younger individuals only) to explore the mechanistic basis for the more rapid atrophy observed in the early days of disuse.
- Conditions
- Muscular Atrophy, Immobility Syndrome
- Being tested
- Single leg immobilisation
- Medical subject headings
- Muscular Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single leg immobilisationBehavioural
Immobilisation with single leg suspension immobilisation
| Study group | Role | What they receive |
|---|---|---|
| 15 Day immobilisation | Experimental | The dominant leg of young healthy patients (18-40 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 15 continuous days Receives: Behavioral: Single leg immobilisation |
| 5 Day immobilisation young | Experimental | The dominant leg of young healthy patients (18-40 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 5 continuous days Receives: Behavioral: Single leg immobilisation |
| 5 Day immobilisation old | Experimental | The dominant leg of aged patients (65-80 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 5 continuous days Receives: Behavioral: Single leg immobilisation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in muscle volume (cm3)
MRI assessment of muscle volume in Tibialis Anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised leg, pre and post immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Changes in muscle thickness (cm)
Ultrasound scan (USS) assessment of muscle thickness in Tibialis Anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised leg, pre and post immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Changes in muscle cross surface area (cm2)
Ultrasound assessment of muscle cross surface area, in tibialis anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised pre and post immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Changes in muscle fibre length (cm)
Ultrasound assessment of muscle fibre length in tibialis anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised pre and post immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Changes in muscle fibre pennation angle (degrees)
Ultrasound assessment of muscle fibre pennation angle in tibialis anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised pre and post immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Muscle Protein Synthesis (MPS) rate (%/hr)
IV tracer (Individual muscle MPS in TA+MG muscles in immobilised vs non immobilised legs)
Measured: Over 8 hours following immobilisation period
Muscle Protein Breakdown (MPB) rate (%/hr)
IV Pulse tracers (IV tracers to give muscle specific MPB measures of TA+MG muscles in immobilised vs non-immobilised legs)
Measured: Over 8 hours following immobilisation period
Secondary outcomes (10)
Muscle blood flow
contrast enhanced ultrasound (CEUS) assessment of muscle blood flow in immobilised vs non-immobilised legs (TA+MG muscle specific)
Measured: over 5 minutes (following immobilisation period)
Leg blood flow
Doppler assessment of leg blood flow through common femoral artery in fed and fasted states in both immobilised and non-immobilised leg
Measured: Over 5 minutes (following immobilisation period)
Anabolic Signalling
Measurement of anabolic signalling pathways by western blot (comparison between immobilised vs non immobilised TA + MG muscles)
Measured: 14 days in group 1. 5 days in groups 2 and 3
Catabolic Signaling
Measurement of proteasome and lysosomal and related catabolic signalling pathways by western blot (comparison between immobilised vs non immobilised TA + MG muscles)
Measured: 14 days in group 1. 5 days in groups 2 and 3
RNA sequencing
complete RNA sequencing of immobilised vs non immobilised TA + MG muscles to determine gene set enrichment and pathway analysis
Measured: 14 days in group 1. 5 days in groups 2 and 3
Histology
Morphological assessment of muscle fibres by histological techniques (comparing immobilised vs non immobilised TA + MG muscles)
Measured: 14 days in group 1. 5 days in groups 2 and 3
Mitochondrial respiration
Measurement of mitochondrial respiration to assess different complex activity in immobilised vs non-immobilised TA + MG muscles
Measured: 14 days in group 1. 5 days in groups 2 and 3
Intramuscular electromyography (iEMG)
Electrically induced maximum force development and fatigability in TA + MG muscles pre and post immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Muscle power
Assessment of changes in muscle power secondary to immobilisation through 1 rep max (kg) pre and post immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Cardio pulmonary fitness
Cardiopulmonary Exercise Testing (CPET) to assess changes in aerobic fitness (V02 max, anaerobic threshold and Watt Max) following immobilisation
Measured: 14 days in group 1. 5 days in groups 2 and 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start1 Apr 2019
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Single group
- Model description
- unilateral limb immobilisation study
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Biotechnology and Biological Sciences Research Council
- Responsible party
- Principal investigator, Bethan Phillips, University of Nottingham
- Investigators
- Bethan E Phillips, PhD, Principal investigator, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04199923
- Sponsor's protocol ID
- 1031809
- Acronym
- iMOB
- Status last verified
- Apr 2025
- First submitted
- 26 Nov 2019
- Last updated
- 2 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Harnessing Muscle-specific Atrophy Susceptibility to Disentangle the Mechanisms of Disuse Atrophy in Human Skeletal Muscle Atrophy (iMOB)
- ClinicalTrials.gov ID
- NCT04199923
- Acronym / sponsor ID
- iMOB / 1031809
- Conditions
- Muscular Atrophy, Immobility Syndrome
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Biotechnology and Biological Sciences Research Council
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 16 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Loss of muscle can be caused by a variety of stimuli and results in reduced mobility and strength and also impacts whole body health. Whilst it is known that muscles waste the process by which this occurs is not well understood. Furthermore, whilst some muscles waste quickly others seem resistant to the effects of disuse.
This study aims to evaluate how quickly changes in muscles start to occur, and investigate the processes which underlie muscle atrophy. By studying muscles which waste quickly and those which are resistant to atrophy this study aims to identify the different processes which lead to muscle loss. This study will also evaluate the differences in muscle changes between young and old people.
Detailed description
Skeletal muscles host ~40% of all protein in the body. Muscles are not only crucial for locomotion but also represent the body's largest metabolically active tissue, glucose disposal site and fuel reservoir for other organs in pathological conditions (i.e., supply of amino acids to the liver for gluconeogenesis). Muscle atrophy is characterized by a reduction in cross sectional area (CSA) and length and occurs in many common illnesses (e.g. cancers (1), renal/heart failure, sepsis, genetic diseases, neurodegenerative disorders etc). It is also prevalent in situations of reduced neural input such as leg casting after fractures (2), bed-rest, spinal cord injury (3), space flight and chronic physical inactivity. Atrophy results in a loss of muscle power and strength (which is related to increased morbidity and mortality (4)) and reduced capacities for whole-body glucose storage and metabolism which causes insulin resistance. Strategies to oppose atrophy are limited but include mechanical loading (5) and the synergistic anabolic effects of nutrients. Although muscle atrophy is of great clinical importance, relatively little mechanistic research has been done in humans. Thus, the aim of this study is to assess the link between the variation in muscle physiological responses to disuse atrophy with variation in protein turnover and molecular-networks. This will not only provide new hypotheses for physiological regulation of human muscle and generate 'intervention targets' derived from clinically relevant human studies, it will also improve understanding of whether the response to disuse is altered with age and determine if mechanistic differences in atrophy resistant and atrophy sensitive muscles might explain inter-muscular variation in susceptibility to atrophy.
This study aims to define the molecular and metabolic mechanisms causing disuse atrophy in both young and older individuals and explore how and why some muscles are protected against it. The study will also assess temporal aspects of disuse atrophy (in younger individuals only) to explore the mechanistic basis for the more rapid atrophy observed in the early days of disuse.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- unilateral limb immobilisation study
| Arm | Type | Receives |
|---|---|---|
| 15 Day immobilisation | Experimental | Behavioral: Single leg immobilisationThe dominant leg of young healthy patients (18-40 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 15 continuous days |
| 5 Day immobilisation young | Experimental | Behavioral: Single leg immobilisationThe dominant leg of young healthy patients (18-40 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 5 continuous days |
| 5 Day immobilisation old | Experimental | Behavioral: Single leg immobilisationThe dominant leg of aged patients (65-80 years without serious comorbidities) will be immobilised using a fixed knee brace and aircast boot for 5 continuous days |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Group 1 and 2: Male, Age 18-40, BMI 18-35
- Group 3: Male, Age 65-80, BMI 18-35
Key exclusion criteria (4 listed)
- BMI > 35 / <18
- Female
- Personal or Family History of Venous Thromboembolism
- Significant medical comorbidities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single leg immobilisationImmobilisation with single leg suspension immobilisation | Behavioural | 15 Day immobilisation, 5 Day immobilisation old, 5 Day immobilisation young |
Primary outcome
Changes in muscle volume (cm3)
Time frame: 14 days in group 1. 5 days in groups 2 and 3
MRI assessment of muscle volume in Tibialis Anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised leg, pre and post immobilisation
Changes in muscle thickness (cm)
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Ultrasound scan (USS) assessment of muscle thickness in Tibialis Anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised leg, pre and post immobilisation
Changes in muscle cross surface area (cm2)
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Ultrasound assessment of muscle cross surface area, in tibialis anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised pre and post immobilisation
Changes in muscle fibre length (cm)
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Ultrasound assessment of muscle fibre length in tibialis anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised pre and post immobilisation
Changes in muscle fibre pennation angle (degrees)
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Ultrasound assessment of muscle fibre pennation angle in tibialis anterior (TA) and Medial Gastrocnemius (MG) in immobilised vs non-immobilised pre and post immobilisation
Muscle Protein Synthesis (MPS) rate (%/hr)
Time frame: Over 8 hours following immobilisation period
IV tracer (Individual muscle MPS in TA+MG muscles in immobilised vs non immobilised legs)
Muscle Protein Breakdown (MPB) rate (%/hr)
Time frame: Over 8 hours following immobilisation period
IV Pulse tracers (IV tracers to give muscle specific MPB measures of TA+MG muscles in immobilised vs non-immobilised legs)
10 secondary outcomes
Muscle blood flow
Time frame: over 5 minutes (following immobilisation period)
Leg blood flow
Time frame: Over 5 minutes (following immobilisation period)
Anabolic Signalling
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Catabolic Signaling
Time frame: 14 days in group 1. 5 days in groups 2 and 3
RNA sequencing
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Histology
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Mitochondrial respiration
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Intramuscular electromyography (iEMG)
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Muscle power
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Cardio pulmonary fitness
Time frame: 14 days in group 1. 5 days in groups 2 and 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bethan E Phillips, PhD principal investigator
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Single leg immobilisation in people with Muscular Atrophy and Immobility Syndrome, run by University of Nottingham at 1 site in United Kingdom.
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 2 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Changes in muscle volume (cm3) (time frame: 14 days in group 1. 5 days in groups 2 and 3). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 May 2025.