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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Other | Healthy subjects aged 18 to 35 years |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eccentric exercise | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22 |
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Inclusion Criteria:
Exclusion Criteria:
Criteria Based Upon Diagnostic Assessments:
Other Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Nottingham | NG7 2UH | United Kingdom |
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| Label | URL |
|---|---|
| Results for study 200794 can be found on the GSK Clinical Study Register. | View source |
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| ID | Term |
|---|---|
| D013708 | Tendon Injuries |
| D063806 | Myalgia |
| ID | Term |
|---|---|
| D014947 | Wounds and Injuries |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
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| 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 | 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 | 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 | 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 | Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22 |
| D009422 |
| Nervous System Diseases |
| D059352 | Musculoskeletal Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |