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Completed

NCT Number: NCT05036239

Recovery From 50 Eccentric Biceps Curls in Young, Untrained Men and Women

The purpose of the study is to investigate muscle stiffness in relation to muscle damaging work and to investigate how well the change in muscle stiffness correlates with the degree of muscle damage (myofibrillar disruption and necrosis). To date, the reduction in force-generating capacity is the best non-invasive marker of muscle damage. It is already established that muscle stiffness correlates well with the decline in force-generating capacity after damaging exercise. However, the correlation between degree of muscle damage and muscle stiffness has not yet been investigated. The main focus of the study is therefore to investigate the relationship between muscle stiffness and muscle damage. Further, the researchers aim to investigate how calcium cycling is affected by damaging work, and if impaired calcium cycling may partially explain the observed reduction in force-generating capacity.

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Key information

Age range

18 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Norwegian School of Sport Sciences

Oslo, 0863, Norway

About this study

Regardless of whether an individual is in rehabilitation or exercise for general health or athletic performance, resistance exercise is an essential form of exercise when the goal is to increase muscle mass, strength and function. Although, resistance exercise primarily is associated with positive effects it may also result in muscle damage when the exercise is of high intensity and/or unaccustomed. This is known as exercise-induced muscle damage (EIMD) and is reflected by a substantial decrease in force-generating capacity and often accompanied by intracellular swelling and delayed onset muscle soreness. On a cellular level, EIMD include myofibrillar disruption, inflammatory response and in severe cases of EIMD; myofibre necrosis. While EIMD with its symptoms clearly is evident, its underlying mechanisms are still to be fully elaborated.

One interesting hypothesis regarding the molecular basis of decreased muscle strength as a result of EIMD, is related to the strain of this exercise mode causing "popped" sarcomeres. When sarcomeres are stretched beyond actin-myosin overlap, some sarcomeres may over-stretch. This results in overload of membranes, leading to opening of stretch-activated channels, and subsequently influx of Ca2+. High levels of cytoplasmic Ca2+ may cause degradation of contractile proteins or Excitation-Contraction coupling proteins mediated through increased calpain activity. However, a recent study by Cully and colleagues (2017) suggest a protective mechanism post heavy-load strength training related to Ca2+-handling. Cully et al. observed formation of vacuoles in longitudinally connecting tubules post exercise when exposing fibers to 1.3 μM [Ca2+] in the cytoplasma. These vacuoles provide an enclosed compartment where Ca2+ can be accumulated, preventing Ca2+ from initiating damage to the muscle. The role of Ca2+-regulation in recovery of muscle function warrants further investigation and clarification.

To the best of the investigators knowledge, the most valid method for estimating EIMD is by investigating myofibrillar disruption, and in some cases necrosis, in muscle biopsies. This requires many resources and is rather expensive. Currently, the best non-invasive marker of muscle damage is the force deficit observed at 48 hours post exercise. However, a measurement estimating muscle damage immediately post exercise is warranted because force deficit immediately post exercise will be confounded by muscle fatigue.

A novel study performed by Lacourpaille et al. (2017) showed a strong negative correlation (-0.80) between stiffness of the muscle tissue, shear modulus, measured 30 minutes post exercise and peak isometric force measured at 48 hours post exercise and therefore a strong relationship between the decline in force production capacity and increased stiffness post exercise, suggesting a possible method to predict EIMD immediately after exercise. However, direct evidence of this association is warranted, with measurements of shear modulus and EIMD biomarkers, such as the proportion of disrupted fibers and sarcoplasmic Ca2+ regulation.

The ability to predict EIMD after training is of great interest to athletes, but also patients suffering from e.g. muscular dystrophies. Being able to predict EIMD quickly and non-invasively after exercise will help employ optimal recovery.

The aim of this project is to investigate the link between exercise-induced muscle damage (EIMD) as changes in shear modulus by ultrasound shear wave elastography, and muscle damage as observed in the analysis of muscle biopsies. The hypothesis is that there is a strong relationship between muscle stiffness acute post exercise and degree of muscle damage observed in muscle biopsies. A secondary aim is to further the understanding of cellular mechanisms causing EIMD and the role of Ca2+ in the recovery of muscle function.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • 18 to 35 years of age

Exclusion criteria

  • Injury to the muscle-skeletal system
  • Other conditions causing inability to perform heavy-load resistance exercise
  • Having engaged in resistance exercise targeting the m. biceps brachii once a week or more over the past year

Treatment and study plan

Eccentric biceps curls

Other

10 x 5 repetitions of eccentric biceps curls, interspaced by 30 seconds of rest.

Primary outcomes

  1. Change in muscle strength

    Time frame: Baseline, and 5 minutes, 3 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls

    Recovery of arm flexion torque

  2. Change in muscle stiffness

    Time frame: Baseline, and 50 minutes, 3 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls

    Muscle stiffness measured with shear wave elastography as mean young modulus in different conditions (static and dynamic)

  3. Change in muscle damage

    Time frame: 2 hours, 48 hours, and 96 hours after eccentric biceps curls

    Development of myofibrillar disruption and necrosis observed in skeletal muscle biopsies with electron and confocal microscopy

  4. Change in calcium cycling

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Calcium cycling in muscle single fibers and Sarcoplasmic reticulum-homogenate

Secondary outcomes

  1. Change in organization of the tubular system in skeletal muscle

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Quantification of transverse and longitudinal tubules, and number of Vacuoles in single fibers using confocal microscopy

Other outcomes

  1. Change in HSP70

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Localization of HSP70 in skeletal muscle using Western blotting

  2. Change in AlphaB-crystallin

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Localization of alphaB-crystallin in skeletal muscle using Western blotting

  3. Change in Fiber-specific AlphaB-crystallin staining intensity

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Change in staining intensity of AlphaB-crystallin in type-I and type-II skeletal muscle fibers using Immunohistochemistry

  4. Change in Fiber-specific HSP70 staining intensity

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Change in staining intensity of HSP70 in type-I and type-II skeletal muscle using Immunohistochemistry

  5. Change in Fatigue

    Time frame: Baseline and 1 hour after eccentric biceps curls

    Electrical stimulation of m. biceps brachii at 20 and 50 Hz

  6. Change in Muscle soreness

    Time frame: Baseline, 15 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls

    Subjective rating of muscle soreness using a VAS-scale (0-10)

  7. Change in Muscle swelling (circumference)

    Time frame: Baseline, 15 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls

    Circumference of upper arm measured 2 cm above humeral epicondyles and midbelly of m. biceps brachii

  8. Change in Muscle swelling (thickness)

    Time frame: Baseline, 2 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls

    Thickness at midbelly of m. biceps brachii using ultrasound B-mode

  9. Change in Creatine kinase

    Time frame: Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls

    Level of serum creatine kinase

  10. Change in Myoglobin

    Time frame: Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls

    Level of serum myoglobin

  11. Change in Titin

    Time frame: Baseline, 2,5 hours, morning day 2, morning day 3, morning day 4, and morning day 5 after eccentric biceps curls

    Level of titin-N fragment in urine

  12. Change in Troponin I

    Time frame: Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls

    Level of serum Troponin I in fast and slow twitch muscle fibers

  13. Change in Macrophage infiltration

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Presence of macrophages in skeletal muscle using Immunohistochemistry

  14. Muscle fiber type

    Time frame: 2 hours after eccentric biceps curls

    Fiber type composition in cross-sections of muscle samples using Immunohistochemistry

  15. Muscle fiber type

    Time frame: 48 hours after eccentric biceps curls

    Fiber type composition in cross-sections of muscle samples using Immunohistochemistry

  16. Muscle fiber type

    Time frame: 96 hours after eccentric biceps curls

    Fiber type composition in cross-sections of muscle samples using Immunohistochemistry

  17. Change in Calcium-related protein abundances in skeletal muscle

    Time frame: 2 hours, 48 hours and 96 hours after eccentric biceps curls

    Levels of proteins and phosphorylation status using Western blotting

Sponsors and collaborators

Lead sponsor

Norwegian School of Sport Sciences

Other

Collaborators

  • Oslo University Hospital
  • Syddansk Universitet, Denmark
  • University of Copenhagen
  • University of Oslo
  • Université de Nantes

Registry information

Official study title

Recovery After Exercise-Induced Muscle Damage

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Sep 5, 2021
Registry last updated
Nov 30, 2023

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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