Clinical trial NCT05036239: Recovery From 50 Eccentric Biceps Curls in Young, Untrained Men and Women
Official title: Recovery After Exercise-Induced Muscle Damage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Recovery
Muscle Damage
Muscle Stiffness
Cell Structure Alteration
Calcium Cycling
Lead sponsor: Norwegian School of Sport Sciences
Sponsor class: OTHER
Collaborators: name: Université de Nantes
name: Oslo University Hospital
name: University of Oslo
name: Syddansk Universitet, Denmark
name: University of Copenhagen
First posted: 2021-09-05
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants perform one bout of eccentric exercise with one arm, while the contralateral arm serves as control. Which arm who receives eccentric exercise is randomized between dominant/non-dominant arm.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in muscle strength
timeFrame: Baseline, and 5 minutes, 3 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
measure: Change in muscle stiffness
timeFrame: Baseline, and 50 minutes, 3 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
measure: Change in muscle damage
timeFrame: 2 hours, 48 hours, and 96 hours after eccentric biceps curls
measure: Change in calcium cycling
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
Secondary outcomes:
measure: Change in organization of the tubular system in skeletal muscle
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
Other outcomes:
measure: Change in HSP70
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
measure: Change in AlphaB-crystallin
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
measure: Change in Fiber-specific AlphaB-crystallin staining intensity
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
measure: Change in Fiber-specific HSP70 staining intensity
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
measure: Change in Fatigue
timeFrame: Baseline and 1 hour after eccentric biceps curls
measure: Change in Muscle soreness
timeFrame: Baseline, 15 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls
measure: Change in Muscle swelling (circumference)
timeFrame: Baseline, 15 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls
measure: Change in Muscle swelling (thickness)
timeFrame: Baseline, 2 minutes, 23 hours, 47 hours, 71 hours, and 95 hours after eccentric biceps curls
measure: Change in Creatine kinase
timeFrame: Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
measure: Change in Myoglobin
timeFrame: Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
measure: Change in Titin
timeFrame: Baseline, 2,5 hours, morning day 2, morning day 3, morning day 4, and morning day 5 after eccentric biceps curls
measure: Change in Troponin I
timeFrame: Baseline, 2,5 hours, 24 hours, 48 hours, 72 hours, and 96 hours after eccentric biceps curls
measure: Change in Macrophage infiltration
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
measure: Muscle fiber type
timeFrame: 2 hours after eccentric biceps curls
measure: Muscle fiber type
timeFrame: 48 hours after eccentric biceps curls
measure: Muscle fiber type
timeFrame: 96 hours after eccentric biceps curls
measure: Change in Calcium-related protein abundances in skeletal muscle
timeFrame: 2 hours, 48 hours and 96 hours after eccentric biceps curls
Locations:
city: Oslo
country: Norway
facility: Norwegian School of Sport Sciences
Study officials:
affiliation: Norwegian School of Sport Sciences
name: Truls Raastad, PhD
role: PRINCIPAL_INVESTIGATOR
References: