Mechanisms of Disuse Atrophy in Human Skeletal Muscle (iMOB)

NCT ID: NCT04199923

Last Updated: 2025-05-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2026-10-01

Brief 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. 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.

Conditions

Muscular Atrophy; Immobility Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

15 Day immobilisation

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

Group Type: EXPERIMENTAL

Single leg immobilisation

Intervention Type: BEHAVIORAL

Immobilisation with single leg suspension immobilisation

5 Day immobilisation young

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

Group Type: EXPERIMENTAL

Single leg immobilisation

Intervention Type: BEHAVIORAL

Immobilisation with single leg suspension immobilisation

5 Day immobilisation old

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

Group Type: EXPERIMENTAL

Single leg immobilisation

Intervention Type: BEHAVIORAL

Immobilisation with single leg suspension immobilisation

Interventions

Single leg immobilisation

Immobilisation with single leg suspension immobilisation

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Group 1 and 2: Male, Age 18-40, BMI 18-35
• Group 3: Male, Age 65-80, BMI 18-35

Exclusion Criteria

• BMI > 35 / <18
• Female
• Personal or Family History of Venous Thromboembolism
• Significant medical comorbidities

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Biotechnology and Biological Sciences Research Council

OTHER

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Bethan Phillips

Professor of Translational Physiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bethan E Phillips, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Nottingham

Locations

Graduate Entry Medical School

Derby, Derbyshire, United Kingdom

Countries

United Kingdom

Other Identifiers

1031809

Identifier Type: -

Identifier Source: org_study_id