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Completed

NCT Number: NCT03559452

Muscle Damage and Disuse Atrophy

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.

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Key information

Conditions

Muscle Disuse Atrophy Inflammation Muscular Diseases Muscular Disorders, Atrophic Musculoskeletal Diseases Nervous System Diseases Neuromuscular Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Exeter

Exeter, Devon, EX1 2LU, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Eccentric exercise

Procedure

300 eccentric contractions of the knee extensors

Primary outcomes

  1. Change in thigh muscle volume from pre-immobilisation

    Time frame: After 2 days of 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.

  2. Change in thigh muscle volume from pre-immobilisation

    Time frame: After 7 days of 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 outcomes

  1. Change in unilateral knee extensor 1 repetition maximum

    Time frame: After 7 days of immobilisation

    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

  2. Change in unilateral knee extensor maximal voluntary torque production

    Time frame: After 7 days of immobilisation

    Unilateral knee extensor maximal voluntary torque production will be measured before and after 7 days of single leg immobilisation using an isokinetic dynamometer.

  3. Change in unilateral knee extensor isokinetic total work

    Time frame: After 7 days of immobilisation

    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.

  4. Muscle protein synthesis assessed using the stable isotope Deuterium Oxide

    Time frame: After 2 days of immobilisation

    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).

  5. Muscle protein synthesis assessed using the stable isotope Deuterium Oxide

    Time frame: After 7 days of immobilisation

    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).

  6. Change in skeletal muscle gene expression

    Time frame: After 2 days of immobilisation

    Skeletal muscle gene expression will be measured before and after 2 days of single leg immobilisation.

  7. Change in skeletal muscle gene expression

    Time frame: After 7 days of immobilisation

    Skeletal muscle gene expression will be measured before and after 7 days of single leg immobilisation.

Sponsors and collaborators

Lead sponsor

University of Exeter

Other

Registry information

Official study 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?

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jun 18, 2018
Registry last updated
Sep 27, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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