Improving Tissue Repair After Injury in the Muscle-tendon Interface Muscle Tissue Injury

Study Overview
=================
Brief Summary
-----------------
The study is a 2-week human study where 40 patients who are scheduled to undergo reconstructive knee surgery are randomized to administration of GH or placebo following or without neuromuscular electrical stimulation of hamstring muscles.The overall aim is to determine, the role of muscle connective tissue protein synthesis in muscle injury and repair.

Official Title
-----------------
Regulation of Protein Turnover in Connective Tissue From Muscle and Tendon Following Muscle Tissue Injury

Conditions
-----------------
Muscle Injury

Intervention / Treatment
-----------------
* Procedure: Electrical stimulation
* Drug: Growth hormone (somatropin)
* Other: Control (No electrical stimulation, nor growth hormone)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy men and women scheduled to undergo reconstructive knee surgery BMI 18-35 Exclusion Criteria: Former or current use of growth hormone or anabolic steroids Use of corticosteroids in the past 3 months Use of any medication known to affect muscle or tendon turnover Former participation in a study using deuterated water Chronic diseases

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1) Electrical stimulation + growth hormone<br>One bout of electrical stimulation with 200 eccentric contractions. This is followed by daily injections with somatropin (33.3 ug/kg in the first week, 50 ug/kg in the second week) for two weeks. | Procedure: Electrical stimulation<br>* Experimentally induced muscly injury via. neuromuscular electrical stimulation of the hamstring muscles<br>Drug: Growth hormone (somatropin)<br>* Daily injection of growth hormone<br>|
| Experimental: 2) Electrical stimulation<br>One bout of electrical stimulation with 200 eccentric contractions | Procedure: Electrical stimulation<br>* Experimentally induced muscly injury via. neuromuscular electrical stimulation of the hamstring muscles<br>|
| Active Comparator: 3) Growth hormone<br>Daily injections with somatropin (33.3 ug/kg in the first week, 50 ug/kg in the second week) for two weeks. | Drug: Growth hormone (somatropin)<br>* Daily injection of growth hormone<br>|
| Placebo Comparator: 4) Control<br>No intervention | Other: Control (No electrical stimulation, nor growth hormone)<br>* No electrical stimulation, nor growth hormone<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in muscle and myotendinous junction protein synthesis in regenerating vs. control muscle | Fractional synthesis rates based on D2O (deuterated water) intake and deuterium labelled alanine in tissue | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in muscle protein synthesis in regenerating muscle, myotendinous junction tissue with or without growth hormone | Fractional synthesis rates based on D2O (deuterated water) intake and deuterium labelled alanine in tissue | 2 years | 
| Single protein synthesis in regenerating vs. control muscle and myotendinous junction tissue | Dynamic proteome profiling fractional synthesis rates based on D2O (deuterated water) intake and deuterium labelled alanine in single proteins | 2 years | 
| Single protein synthesis in regenerating muscle and myotendinous junction tissue with or without growth hormone | Dynamic proteome profiling fractional synthesis rates based on D2O (deuterated water) intake and deuterium labelled alanine in single proteins | 2 years | 
| Tendon tissue synthesis from injured muscle vs. control muscle | FSR based on D2O intake and D-alanine label in tissue | 2 years | 
| Difference in muscle protein synthesis in regenerating muscle, myotendinous junction, and tendon tissue with or without growth hormone | Fractional synthesis rates based on D2O (deuterated water) intake and deuterium labelled alanine in tissue | 2 years | 
| Difference in muscle protein synthesis in regenerating vs. control muscle, myotendinous junction, and tendon tissue | Fractional synthesis rates based on D2O (deuterated water) intake and deuterium labelled alanine in tissue | 2 years | 
| Number of satellite cells, fibroblasts and immune cells in renereting vs. control tissue, with and without growth hormone | Histochemical staining of muscle cross sections | 2 years | 
| Mechanical properties of tissue with and without growth hormone | Ex vivo mechanical stress test | 2 years |