An isolated bout of unaccustomed maximal eccentric exercise is associated with muscle force loss for 2-4 days, mild reversible muscle tenderness, and ultra-structural damage to the muscle fibers, elevation of muscle proteins in serum, and a detriment in range of motion. This single center, pilot study is designed to optimize conditions for the robust measurement of functional deficits after muscle damage and to identify markers of repair over 22 days to inform future intervention studies. The primary measure will be limb force (assessed electronically from the ergometer), previous studies have demonstrated that functional measures return fairly rapidly, usually between 2-4 days. Additionally, several biomarkers of muscle function will be measured over 22 days, as well as changes in protein synthesis in biopsy samples Deuterium-labelled water (D2O) will be consumed by all study participants from Day-3 through Day 22 to aid in quantifying newly synthesized proteins.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
Each subject will perform eccentric exercise against a predefined personal maximal strength of their non-dominant leg on day 1. Changes on strength, biomarker concentrations and muscle protein synthesis during damage and recovery will be measured over 22 days.
GSK Investigational Site
Nottingham, United Kingdom
Change and percent change in maximal leg isometric strength from the baseline up to three weeks after eccentric exercise
Muscle strength is a measure the amount of force produced during a maximal voluntary contraction. Strength will be assessed by a maximal isometric (fixed length) contraction.
Time frame: Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22
Change in peak torque and total work performed over the course of 10 consecutive, maximal isokinetic knee extension and flexion contractions
Each subject will be asked to produce 10 consecutive, maximal isokinetic knee extension and flexion contractions through the full range of motion with the exercised leg on an ergometer
Time frame: Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22
Patient pain assessment using a visual analog scale
Leg pain will be assessed for the exercised leg with a visual analog scale (0-100 mm) before and up to three weeks after eccentric exercise
Time frame: Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22
Change in degree of motion
Each subject will be asked to attempt to move the exercised leg through a full range of motion with zero resistance from baseline up to three weeks after eccentric exercise
Time frame: Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22
Change in plasma CPK and aldolase
Blood sample will be collected to assess CPK and aldolase from baseline and up to three weeks after eccentric exercise
Time frame: Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22
Change in plasma markers
Blood sample will be collected to assess blood inflammatory markers including, but are not limited to, tissue necrosis factor alpha (TNFalpha), interleukin (IL) 1 beta, IL6, IL8, IL10, chemokine ligand (CCL)7, complement 3a (C3a), granulocyte macrophage colony stimulating factor (GM-CSF), and c-reactive protein (CRP) from baseline and up to three weeks after eccentric exercise
Time frame: Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22
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