Timecourse of Immobilization Experiment (TIME)

Short-term Muscle Disuse Induces a Rapid and Sustained Decline in Daily Myofibrillar Protein Synthesis Rates

The effect of unilateral lower limb immobilisation over one week on muscle atrophy

Study Overview

• Status: Completed
• Conditions: Muscular Atrophy
• Intervention / Treatment: Other: Lower limb immobilisation (leg brace)

Detailed Description

This study aims to assess the effect of one week of unilateral leg immobilization on quadriceps muscle volume and muscle protein synthesis rates. Participants wore a leg brace on one leg and ambulated on crutches during the immobilization period. Thirteen healthy young males were recruited to undertake this study.

It is currently understood that unilateral leg immobilization will result in a reduction in muscle size (Berg et al., 1996, Wall et al., 2015) and muscle protein synthesis rates after a period of disuse (de Boer et al., 2015, Glover et al., 2008). Recent research in this area has shown that even short term periods of leg immobilization (i.e. <1 week) will result in reductions in muscle size and muscle protein synthesis rates after the period of disuse (Wall et al., 2015). However we currently do not have detailed information on how muscle disuse affects muscle size and muscle protein synthesis over time during short term disuse (e.g. the first week).

The stable isotope tracer deuterium oxide (D2O) will be applied to assess cumulative muscle protein synthesis between days 0-2, 2-7 and 0-7 of the immobilization period in both the immobilized and non immobilized legs. This will be in-conjunction with bilateral vastus lateralis muscle biopsies before and after 2 and 7 days of immobilization. Furthremore, quadriceps muscle volume was assessed via MRI scans that again occured before and after 2 and 7 days of immobilization. To gain a mechanistic insight on the molecular changes during disuse a custom designed 48 well Taqman low density microarray genecard was applied to assess the transcriptional response on genes involved in muscle protein synthesis and breakdown.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX1 2LU
      • Sport & Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

BMI >18 and <28 no prescription medications or current illness -

Exclusion Criteria:

BMI <18 and >28 current prescription medication no history of leg injury

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Lower limb immobilisation; All participants will undergo 7 days of unilateral leg immobilization. Participants will wear a leg brace (Donjoy X-ACT, DJO Global, USA) on one of their legs which will fix the leg at 40 degrees of flexion for the 7 days. Participants will not be allowed to remove the brace at any stage and are prohibited from bearing weight on the immobilized leg, and will ambulate on crutches throughout the week of immobilization.

Other: Lower limb immobilisation (leg brace)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle size	Quadriceps muscle volume measured via MRI	Days 0, 2 and 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein synthesis	The stable isotope tracer deuterium oxide will be used to assess muscle protein synthesis. In conjunction with bilateral vastus lateralis muscle biopsies before and after 2 and 7 days which allow for the calculation of muscle protein synthesis (fractional synthesis rate) between days 0-2, 2-7 and 0-7.	days 0-2, 2-7 and 0-7
Muscle strength	Skeletal muscle one repetition maximum strength was assessed using standard gym equipment	Pre and post immobilization

Collaborators and Investigators

• Sponsor: University of Exeter

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): October 1, 2019

Study Registration Dates

• First Submitted: December 2, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (ESTIMATE): December 6, 2016

Study Record Updates

• Last Update Posted (ACTUAL): November 8, 2019
• Last Update Submitted That Met QC Criteria: November 6, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Muscular Atrophy
• Other Study ID Numbers: 650061958

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO