Cartilage Adaptation and Response to Interleukins and Exercise

Study Overview
=================
Brief Summary
-----------------
This study will examine the effect of exercise on the turnover of collagen in articular cartilage and the content of cytokines in the synovial fluid from human adults with osteoarthritis.

Detailed Description
-----------------
By using stabile isotope labelling, this study will track the formation and destination of newly formed cartilage collagen in adult humans scheduled for knee replacement surgery due to osteoarthritis. The collagen formation as well as the effect on the cytokine content of the synovial fluid will be examined both at rest and in response to 4 weeks of exercise/training. Overall the project aims to improve the basic understanding of cartilage development and function in relation to osteoarthritis prevention.

Official Title
-----------------
The Effect of Exercise on the Collagen Synthesis and Cytokine Response in Human Cartilage Tissue With Osteoarthritis

Conditions
-----------------
Osteo Arthritis Knee

Intervention / Treatment
-----------------
* Behavioral: Exercise.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Primary osteoarthritis of the knee scheduled for knee replacement surgery Must be able to perform physical exercise Age 40-90 years old BMI 18.5-40 kg/m^2 None smoker for the last 6 weeks Exclusion Criteria: Regular intake of: non steroid anti-inflammatory drugs (NSAID) corticoid-steroids disease modifying anti-rheumatic drugs (DMARD) cytostatic incl. chemotherapy immune suppressive medicine Inflammatory diseases or cancer Recent trauma to the knee (< 3 months) Previous knee surgery Regular strenuous exercise ( > 1 pr. month) Previous exposure to tracers (e.g. from another study)

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 90 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise group<br> | Behavioral: Exercise.<br>* Moderate to heavy intensity resistance exercise consisting of leg press.<br>|
| No Intervention: Control group<br> | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collagen synthesis in articular cartilage | By using incorporation of stabile isotope tracers measured by gas chromatography, the concentration of newly formed collagen will be measured. | End of study at 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine and enzymes concentration in synovial fluid | By using Enzyme-Linked Immunosorbent Assay (ELISA) the concentration of cytokines in synovial fluid will be measured. | End of study at 4 weeks | 
| Cytokine and enzymes concentration in blood | By using Enzyme-Linked Immunosorbent Assay (ELISA) the concentration of cytokines in the blood will be measured. | At the beginning and at the end of the study at 4 weeks | 
| Gene expression | By using real time reverse transcriptase polymerase chain reaction (RT-PCR) the concentration of messenger ribonucleic acid (mRNA) in cartilage tissue will be measured. | End of study at 4 weeks | 
| Strength | By calculating the total volume of weight lifted (kg) the strength will be measured. | At the beginning and at the end of the study at 4 weeks | 
| Body mass index (BMI) | BMI measured as the total body weight divided by the height squared (kg/m^2) | At the beginning of the study. | 
| Age | The age measured in years | At the beginning of the study. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
exercise, cytokines, collagen