Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function

Study Overview
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Brief Summary
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Ideally, the postoperative inflammatory response is part of a well-orchestrated mechanism that contributes to tissue healing and rapid recovery. An exaggerated uncontrolled inflammatory response, however may lead to catabolism, tissue damage and organ failure. Omega-3 fatty acids may provide a means to alter cellular immune responses to the benefit of the patient. When omega-3 fatty acids are incorporated into membranes of inflammatory cells, they trigger intracellular signalling pathways that result in a less pro-inflammatory response. They modify gene and protein expression, modulate membrane protein activity and act as a reservoir for bioactive molecules. They also have a strong anti-inflammatory effect by mediating resolution of the inflammation. Furthermore, omega-3 fatty acids improve erythrocyte function, which is vital for an adequate microcirculation, tissue oxygenation and wound healing. The investigators hypothesize that the perioperative administration of intravenous omega-3 fatty acids results in a rapid incorporation in immune cells and erythrocytes, thereby reducing the postoperative inflammatory response and improving erythrocyte function in patients undergoing colorectal surgery.

Official Title
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Effect of Intravenous Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function in Patients With Colon Cancer

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: Omegaven
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (male or female) undergoing elective laparoscopic surgery for colon cancer Age between 60 and 80 years BMI between 20 kg/m2 and below 30 kg/m2 Written informed consent Exclusion Criteria: Participation in or having participated in another clinical trial within the previous 3 months Indications for continuously use of anticoagulant medication and no possibility to stop these medication perioperatively, for example patients with an artificial heart valve Pre-operative Hemoglobin<5.0 mmol/L Metastatic disease Very poor peripheral venous access Current history of inflammatory or infectious disease The use of anti-inflammatory drugs The use of thyroid medication The use of fish oil products or fish consumption more than 2 times a week Contra-indication for the use of Omegaven-Fresenius, including: General contra-indications for parenteral nutrition Allergy to fish or egg protein.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>2 infusions of NaCl, 2 ml/kg, one the night before operation and one the day after operation. | Drug: Placebo<br>* 2 infusions, 2 ml/kg, one the night before operation and one the day after operation<br>* Other names: glass container NaCl 0,9% Fresenius Kabi;|
| Active Comparator: Omegaven<br>2 infusions of 2ml/kg, one the night before surgery and one the day after surgery | Drug: Omegaven<br>* 2 infusions, 2 ml/kg, one the night before operation and one the day after operation<br>* Other names: Omegaven-Fresenius;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ex vivo production of pro-inflammatory cytokine IL-6 in LPS stimulated whole blood | Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine IL-6, measured in ng/ml. | baseline, day of surgery, postoperative day 1,2 and 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ex vivo production of TNF-α and IL-10 in LPS stimulated whole blood | Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine TNF-α (tumor necrosis factor-α), and the anti-inflammatory cytokine IL-10 (interleukine-10), both measured in ng/ml. | baseline, day of surgery, postoperative day 1, 2 and 4 | 
| Change in erythrocyte function | Erythrocyte deformability and aggregation measured by LORRCA (laser assisted optical rotational red cell analyzer) | baseline, day of surgery, postoperative day 1, 2 and 4 | 
| Change in in vivo systemic inflammatory response parameters | White blood cell count, C-reactive protein and cytokine levels (Interleukine-6, Tumor Necrosis Factor-α and Interleukine-10) in serum. | baseline, day of surgery, postoperative day 1, 2 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fish oil, omega-3 fatty acids, postoperative inflammatory response, erythrocyte function