Muscle Damage and Disuse Atrophy
Primary Purpose
Muscle Disuse Atrophy
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Eccentric exercise
Sponsored by
About this trial
This is an interventional basic science trial for Muscle Disuse Atrophy focused on measuring Muscle damage, Inflammation, Immobilisation
Eligibility Criteria
Inclusion Criteria:
- Aged 18 - 40
- BMI between 18 and 27
- Healthy, recreationally active, non smoker
Exclusion Criteria:
- Non-removable metallic implants (including heart pacemaker, cochlear implants, medication pumps, surgical clips, plates or screws) or claustrophobia
- Use of nutritional supplements
- Chronic use of over the counter medication
- Any diagnosed metabolic disease (e.g. type 1 or 2 Diabetes).
- Any diagnosed cardiovascular disease or hypertension.
- Anyone with previous motor disorders. Anyone with a current musculoskeletal injury that may impair their use of crutches.
Sites / Locations
- University of Exeter
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control
Muscle damage
Arm Description
Immobilisation without prior exercise
300 bilateral knee extensor eccentric contraction performed immediately prior to immobilisation
Outcomes
Primary Outcome Measures
Change in thigh muscle volume from pre-immobilisation
The volume of the muscles comprising the thigh after 2 days of immobilisation will be compared to pre-immobilisation values. This will be measured using MRI.
Change in thigh muscle volume from pre-immobilisation
The volume of the muscles comprising the thigh after 7 days of immobilisation will be compared to pre-immobilisation values, and values obtained after 2 days of immobilisation. This will be measured using MRI.
Secondary Outcome Measures
Change in unilateral knee extensor 1 repetition maximum
Unilateral knee extensor 1 repetition maximum will be measured before and after 7 days of single leg immobilisation using a weight stack leg extension machine
Change in unilateral knee extensor maximal voluntary torque production
Unilateral knee extensor maximal voluntary torque production will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.
Change in unilateral knee extensor isokinetic total work
Unilateral knee extensor total isokinetic work after 30 consecutive contractions will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide
The enrichment of deuterated alanine (from the deuterium oxide heavy water stable isotope tracer) in vastus lateralis biopsy samples will be measured relative to the non-deuterated alanine. The change between pre-immobilisation and 2 days of immobilisation will be used to calculated a fractional synthetic rate (% day).
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide
The enrichment of deuterated alanine (from the deuterium oxide heavy water stable isotope tracer) in vastus lateralis biopsy samples will be measured relative to the non-deuterated alanine. The change between pre-immobilisation and 7 days of immobilisation will be used to calculated a fractional synthetic rate (% day).
Change in skeletal muscle gene expression
Skeletal muscle gene expression will be measured before and after 2 days of single leg immobilisation.
Change in skeletal muscle gene expression
Skeletal muscle gene expression will be measured before and after 7 days of single leg immobilisation.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03559452
Brief Title
Muscle Damage and Disuse Atrophy
Official Title
In Young Healthy Males and Females, What is the Effect of Prior Eccentric Exercise on Thigh Muscle Atrophy During One Week of Leg Disuse Compared to no Prior Exercise?
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
October 31, 2019 (Actual)
Study Completion Date
October 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Exeter
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Limb injury generally requires a period of recovery during which time the limb is often immobilised (e.g. with a cast or brace) resulting in a rapid loss of skeletal muscle. Despite the importance of muscle loss during injury, our understanding of how it occurs is incomplete. Several factors are likely to contribute, including a lack of muscle contraction and injury induced inflammation. In this study, the investigators will recruit healthy volunteers who will spend 7 days in a knee brace to replicate leg immobilisation. Prior to immobilisation, half of the participants will perform a single session of strenuous resistance exercise which is known to cause muscle damage and initiate an inflammatory response. This is designed to replicate the muscle damage and inflammation that occurs with injury. The remaining half of participants will not perform this exercise, allowing us to look at the additive effect of muscle damage and inflammation on muscle loss with immobilisation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Disuse Atrophy
Keywords
Muscle damage, Inflammation, Immobilisation
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
No Intervention
Arm Description
Immobilisation without prior exercise
Arm Title
Muscle damage
Arm Type
Experimental
Arm Description
300 bilateral knee extensor eccentric contraction performed immediately prior to immobilisation
Intervention Type
Procedure
Intervention Name(s)
Eccentric exercise
Intervention Description
300 eccentric contractions of the knee extensors
Primary Outcome Measure Information:
Title
Change in thigh muscle volume from pre-immobilisation
Description
The volume of the muscles comprising the thigh after 2 days of immobilisation will be compared to pre-immobilisation values. This will be measured using MRI.
Time Frame
After 2 days of immobilisation
Title
Change in thigh muscle volume from pre-immobilisation
Description
The volume of the muscles comprising the thigh after 7 days of immobilisation will be compared to pre-immobilisation values, and values obtained after 2 days of immobilisation. This will be measured using MRI.
Time Frame
After 7 days of immobilisation
Secondary Outcome Measure Information:
Title
Change in unilateral knee extensor 1 repetition maximum
Description
Unilateral knee extensor 1 repetition maximum will be measured before and after 7 days of single leg immobilisation using a weight stack leg extension machine
Time Frame
After 7 days of immobilisation
Title
Change in unilateral knee extensor maximal voluntary torque production
Description
Unilateral knee extensor maximal voluntary torque production will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.
Time Frame
After 7 days of immobilisation
Title
Change in unilateral knee extensor isokinetic total work
Description
Unilateral knee extensor total isokinetic work after 30 consecutive contractions will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.
Time Frame
After 7 days of immobilisation
Title
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide
Description
The enrichment of deuterated alanine (from the deuterium oxide heavy water stable isotope tracer) in vastus lateralis biopsy samples will be measured relative to the non-deuterated alanine. The change between pre-immobilisation and 2 days of immobilisation will be used to calculated a fractional synthetic rate (% day).
Time Frame
After 2 days of immobilisation
Title
Muscle protein synthesis assessed using the stable isotope Deuterium Oxide
Description
The enrichment of deuterated alanine (from the deuterium oxide heavy water stable isotope tracer) in vastus lateralis biopsy samples will be measured relative to the non-deuterated alanine. The change between pre-immobilisation and 7 days of immobilisation will be used to calculated a fractional synthetic rate (% day).
Time Frame
After 7 days of immobilisation
Title
Change in skeletal muscle gene expression
Description
Skeletal muscle gene expression will be measured before and after 2 days of single leg immobilisation.
Time Frame
After 2 days of immobilisation
Title
Change in skeletal muscle gene expression
Description
Skeletal muscle gene expression will be measured before and after 7 days of single leg immobilisation.
Time Frame
After 7 days of immobilisation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Aged 18 - 40
BMI between 18 and 27
Healthy, recreationally active, non smoker
Exclusion Criteria:
Non-removable metallic implants (including heart pacemaker, cochlear implants, medication pumps, surgical clips, plates or screws) or claustrophobia
Use of nutritional supplements
Chronic use of over the counter medication
Any diagnosed metabolic disease (e.g. type 1 or 2 Diabetes).
Any diagnosed cardiovascular disease or hypertension.
Anyone with previous motor disorders. Anyone with a current musculoskeletal injury that may impair their use of crutches.
Facility Information:
Facility Name
University of Exeter
City
Exeter
State/Province
Devon
ZIP/Postal Code
EX1 2LU
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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Muscle Damage and Disuse Atrophy
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