Skeletal Muscle Strain Injuries and the Connective Tissue: Characterization, Recovery and Optimal Treatment

Study Overview
=================
Brief Summary
-----------------
Firstly, the investigators aim to study the biochemical, structural and functional changes associated with acute muscle strain injury in the acute phase and during rehabilitation in vivo. Specific factors present after the injury and their effects on connective tissue cells will be examined in vitro. Secondly, the investigators will investigate individuals with chronic pain, scar tissue and inferior function after a previous muscle strain injury and test a specific rehabilitation program to alleviate pain and disabilities associated with the preceding muscle injury. The investigators have the following hypotheses: Humoral growth factors and pro-inflammatory macrophages released into the injured area post strain injury stimulate formation of connective tissue in vitro. Early onset of rehabilitation will be superior to a delayed start of rehabilitation for the healing process, in regards to structural improvement of tissue and better clinical function. Scar tissue following a muscle strain injury is characterized by disorganized structure of connective tissue. Mechanical loading in the form of heavy eccentric muscle activity for 12 weeks will lead to a local re-modeling of scar tissue, and result in improved function and reduced symptoms in patients with chronic pain and impaired function after a previous muscle injury.

Official Title
-----------------
Skeletal Muscle Strain Injuries and the Connective Tissue: Characterization, Recovery and Optimal Treatment

Conditions
-----------------
Muscle Strain

Intervention / Treatment
-----------------
* Procedure: Acute Early onset of rehabilitation
* Procedure: Acute Delayed onset of rehabilitation
* Procedure: Chronic Exercise
* Procedure: Chronic Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Acute muscle strain injury Chronic muscle strain injury Age above 18 years Exclusion Criteria: Daily intake of non-steroidal anti-inflammatory drugs (NSAIDs) within three months prior to the injury Smoking Diabetes Connective tissue and/or rheumatic diseases Any observed organ dysfunctions

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic Exercise<br>Chronic Exercise | Procedure: Chronic Exercise<br>* Exercise<br>|
| Experimental: Acute Early onset of rehabilitation<br>Acute Early onset of rehabilitation | Procedure: Acute Early onset of rehabilitation<br>* Early onset of rehabilitation<br>|
| Experimental: Chronic control<br>Chronic control | Procedure: Chronic Control<br>* Control<br>|
| Experimental: Acute Delayed onset of rehabilitation<br>Acute Delayed onset of rehabilitation | Procedure: Acute Delayed onset of rehabilitation<br>* Delayed onset of rehabilitation<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Return to full physical activity | First time the subject is fully fit to take part in all types of physical activity post injury; | Baseline; Up to 30 weeks (estimated time frame maximum) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Magnetic resonance images | Size of injured tissue; Size and location of hematoma; Measurement of muscle perfusion (indication of metabolic activity) | Baseline, 4 weeks, 6 weeks, 12 weeks, 6 months | 
| Ultrasound images | Size and location of injury | Baseline, 7-14 days, 4 weeks, 6 weeks, 12 weeks, 6 months | 
| Ultrasound images | Volume of hematoma | Baseline, 1 week, 2 weeks | 
| Strength measurements | Strength tests of injured muscle group compared to healthy muscle group on contralateral leg | Baseline, 4 weeks, 6 weeks, 9 weeks, 12 weeks, 6 months | 
| Structural changes of tissue | Evaluation of tissue samples from injured muscle before and after rehabilitation program | Baseline, 12 weeks | 
| Aspiration and characterization of inter-/ intramuscular fluid in the injured muscle | The aspirated fluid (hematoma/exudate) will be analyzed for released humoral factors, cell types present and its effect on human fibroblast proliferation | Baseline, 3 -14 days |