A Methodology Study to Assess Muscle Damage After Eccentric Exercise

NCT02014662 | Completed Phase 1

• 1 other identifier: 200794
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tendon Injuries

Keywords

Muscle function, Muscle damage and recovery, Eccentric exercise, Muscle soreness, Protein synthesis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Change in peak torque and total work performed over the course of 10 consecutive, maximal isokinetic knee extension and flexion contractions

  Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22

• Patient pain assessment using a visual analog scale

  Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22

• Change in degree of motion

  Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22

• Change in plasma CPK and aldolase

  Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22

• Change in plasma markers

  Day 1, 2, 3, 4, 6, 8, 11, 17 and Day 22

Study Arms (1)

Arm 1

OTHER

Healthy subjects aged 18 to 35 years

Other: Eccentric exercise

Interventions

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.

Arm 1

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males aged between 18 and 35 years of age inclusive, at the time of signing the informed consent, not on a regular exercise program.
• Body Mass Index (BMI) 18-27 kilogram per meter square (kg/m\^2) with waist circumference \<96 centimeter (cm).

You may not qualify if:

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Based on single or averaged corrected QT interval (QTc) (Bazzett \[QTcB\] or Fredericia \[QTcF\]) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QTc \<450 milliseconds (msec); or QTc \< 480 msec in subjects with Bundle Branch Block.
• At least a 1year history of no regular (2-3 times per week) exercise and no heavy exertion within past week.
• History of keloid scarring
• History of dizziness or vertigo
• History of bleeding disorders or elevated partial thromboplastin time/international normalized ratio (PTT/INR) at screening, or currently on anticoagulants
• Taking anti-inflammatory, glucocorticoid or other pain medication more than 2 times per week over the previous month.
• Taking regular statin medication.
• Herbal supplement use
• History of smoking or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• History of drug or alcohol abuse within 5 years prior to the Screening Period.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units. One unit is equivalent to 8 gram (gm) of alcohol: a half-pint (\~240 milliliter \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• History of sensitivity to local anesthetics.
• History of sensitivity to any drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Nottingham, NG7 2UH, United Kingdom

Location

Related Links

• Results for study 200794 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Tendon Injuries; Myalgia

Condition Hierarchy (Ancestors)

Wounds and Injuries; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Musculoskeletal Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2013
• First Posted: December 18, 2013
• Study Start: January 14, 2014
• Primary Completion: July 2, 2014
• Study Completion: July 2, 2014
• Last Updated: May 15, 2017

Record last verified: 2017-05

Locations

GB (1)