Mechanisms of Disuse Atrophy in Human Skeletal Muscle (iMOB)

NCT04199923 | Active Not Recruiting

• 1 other identifier: 1031809
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscular Atrophy; Immobility Syndrome

Outcome Measures

Primary Outcomes (7)

• 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

  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

  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

  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

  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

  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)

  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)

  Over 8 hours following immobilisation period

Secondary Outcomes (10)

• Muscle blood flow

  over 5 minutes (following immobilisation period)

• Leg blood flow

  Over 5 minutes (following immobilisation period)

• Anabolic Signalling

  14 days in group 1. 5 days in groups 2 and 3

• Catabolic Signaling

  14 days in group 1. 5 days in groups 2 and 3

• RNA sequencing

  14 days in group 1. 5 days in groups 2 and 3

Study Arms (3)

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

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

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

Behavioral: Single leg immobilisation

Interventions

Single leg immobilisation BEHAVIORAL

Immobilisation with single leg suspension immobilisation

15 Day immobilisation; 5 Day immobilisation old; 5 Day immobilisation young

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Nottingham: lead
• Biotechnology and Biological Sciences Research Council: collaborator

Study Sites (1)

Graduate Entry Medical School

Derby, Derbyshire, DE22 3DT, United Kingdom

Location

MeSH Terms

Conditions

Muscular Atrophy

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Bethan E Phillips, PhD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Translational Physiology

Model Details: unilateral limb immobilisation study

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: December 16, 2019
• Study Start: April 1, 2019
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)