Mechanisms of Tissue Repair After Muscle Injury and Tendon Strain

Study Overview
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Brief Summary
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The study is a 5-week human study including 24 18-35 year old healthy men. Each participant will have muscle injury and tendon strain induced in one leg using neuromuscular electrical stimulation in conjunction with forced lengthening contractions. The investigators will monitor the recovery from injury/strain over a 4 week period, in which half of the subjects will receive growth hormone (somatropin) to stimulate the connective tissue synthesis.

Official Title
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Regulation of Human Tendon and Skeletal Muscle Protein Turnover Following Tissue Injury: Mechanisms Behind Regeneration and Injury Preventive Adaptations

Conditions
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Muscle; Injury, Quadriceps (Thigh), Tendon Strain

Intervention / Treatment
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* Other: Neuromuscular electrical stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men BMI between 18.5-30 kg/m^2 Exclusion Criteria: Smoking Regular strength training within the last 3 months Current or former use of anabolic steroids or growth hormone Use of corticosteroids in the last 3 months Use of blood thinning medication Use of medication which can affect muscle protein synthesis Current or former drug og alcohol abuse Knee pain Previous participation in studies using deuterated water or alanine tracers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Growth hormone/somatropin<br>Somatropin over two weeks (33.3 ug/kg/day in the first week, 50 ug/kg/day in the second week) | Other: Neuromuscular electrical stimulation<br>* One bout of neuromuscular electrical stimulation in conjunction with forced lengthening contractions on one leg<br>* Other names: Neuromuscular electrical stimulation using Theta 4 channel stimulator from Chattanooga. Coupled with forced eccentric contractions.;|
| Placebo Comparator: Placebo<br>Injections of placebo/saline over two weeks | Other: Neuromuscular electrical stimulation<br>* One bout of neuromuscular electrical stimulation in conjunction with forced lengthening contractions on one leg<br>* Other names: Neuromuscular electrical stimulation using Theta 4 channel stimulator from Chattanooga. Coupled with forced eccentric contractions.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of somatropin on muscle protein synthesis 14 days after injury | The difference in fractional synthesis rate in muscle proteins 14 days after injury with or without 14 days treatment with somatropin. Measured using deuterated water | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle protein synthesis 7 days after injury | The difference in fractional synthesis rate in muscle proteins 7 days after injury vs control (no injury) with or without 7 days treatment with somatropin. Measured using deuterated water | 7 days | 
| Muscle protein synthesis 14 days after injury | The difference in fractional synthesis rate in muscle proteins 14 days after injury compared to control leg (no injury). Measured using deuterated water. | 14 days | 
| Muscle protein breakdown 14 days after injury | The difference in fractional synthesis rate in muscle proteins 14 days after injury vs. control (no injury) with or without 14 days treatment with somatropin. Measured using stable isotop labelled alanine. | 14 days | 
| Muscle protein breakdown 7 days after injury | The difference in fractional synthesis rate in muscle proteins 7 days after injury vs. control (no injury) with or without 7 days treatment with somatropin. Measured using stable isotop labelled alanine. | 7 days | 
| Muscle protein breakdown 28 days after injury | The difference in fractional synthesis rate in muscle proteins 28 days after injury vs. control (no injury) with or without 14 days treatment with somatropin. Measured using stable isotop labelled alanine. | 28 days | 
| Histochemical staining of muscle cross sections 7 days after injury | Number of satellite cells, fibroblasts and immune cells in injured vs. control tissue (no injury), with and without growth hormone. Measured using histochemical staining of muscle cross sections | 7 days | 
| Histochemical staining of muscle cross sections 14 days after injury | Number of satellite cells, fibroblasts and immune cells in injured vs. control tissue (no injury), with and without growth hormone. Measured using histochemical staining of muscle cross sections | 14 days | 
| Histochemical staining of muscle cross sections 28 days after injury | Number of satellite cells, fibroblasts and immune cells in injured vs. control tissue (no injury), with and without growth hormone. Measured using histochemical staining of muscle cross sections | 28 days | 
| The effect of somatropin on tendon tissue synthesis | The difference in fractional synthesis rate in tendon proteins after 7 days placebo/treatment with somatropin. Measured using deuterated water | 7 days | 
| Tendon tissue synthesis 7 days after strain | The difference in fractional synthesis rate in tendon proteins 7 days after strain compared to control leg (no strain). Measured using deuterated water | 7 days | 
| Tendon tissue synthesis 7 days after strain with/without somatropin | The difference in fractional synthesis rate in tendon proteins 7 days after strain compared to control leg (no strain) with or without somatropin. Measured using deuterated water | 7 days | 
| Isometric muscle force output 7 days following injury | The difference in isometric muscle force output 7 days after injury vs. control (no injury) with or without 7 days treatment with somatropin. | 7 days | 
| Isometric muscle force output 14 days following injury | The difference in isometric muscle force output 14 days after injury vs. control (no injury) with or without 14 days treatment with somatropin. | 14 days | 
| Isometric muscle force output 28 days following injury | The difference in isometric muscle force output 28 days after injury vs. control (no injury) with or without 14 days treatment with somatropin. | 28 days |