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

Sponsor

Medical Center Alkmaar (Other)

Overall Status

Completed

CT.gov ID

NCT02231203

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colon Cancer	Drug: Omegaven Drug: Placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 2 infusions of NaCl, 2 ml/kg, one the night before operation and one the day after operation.	Drug: Placebo 2 infusions, 2 ml/kg, one the night before operation and one the day after operation Other Names: NaCl 0,9% Natriumchloride 0,9% glass container NaCl 0,9% Fresenius Kabi
Active Comparator: Omegaven 2 infusions of 2ml/kg, one the night before surgery and one the day after surgery	Drug: Omegaven 2 infusions, 2 ml/kg, one the night before operation and one the day after operation Other Names: purified fish oil omega-3 fatty acids eicosapentaenoicacid (EPA) docosahexaenoicacid (DHA) dl-a- tocopherol (antioxidant) Omegaven-Fresenius

Arm

Intervention/Treatment

Placebo Comparator: Placebo

2 infusions of NaCl, 2 ml/kg, one the night before operation and one the day after operation.

Drug: Placebo

2 infusions, 2 ml/kg, one the night before operation and one the day after operation

Other Names:

NaCl 0,9%

Natriumchloride 0,9%

glass container NaCl 0,9% Fresenius Kabi

Active Comparator: Omegaven

2 infusions of 2ml/kg, one the night before surgery and one the day after surgery

Drug: Omegaven

2 infusions, 2 ml/kg, one the night before operation and one the day after operation

Other Names:

purified fish oil

omega-3 fatty acids

eicosapentaenoicacid (EPA)

docosahexaenoicacid (DHA)

dl-a- tocopherol (antioxidant)

Omegaven-Fresenius

Outcome Measures

Primary Outcome Measures

Change in ex vivo production of pro-inflammatory cytokine IL-6 in LPS stimulated whole blood [baseline, day of surgery, postoperative day 1,2 and 4]
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.

Secondary Outcome Measures

Change in ex vivo production of TNF-α and IL-10 in LPS stimulated whole blood [baseline, day of surgery, postoperative day 1, 2 and 4]
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.
Change in erythrocyte function [baseline, day of surgery, postoperative day 1, 2 and 4]
Erythrocyte deformability and aggregation measured by LORRCA (laser assisted optical rotational red cell analyzer)
Change in in vivo systemic inflammatory response parameters [baseline, day of surgery, postoperative day 1, 2 and 4]
White blood cell count, C-reactive protein and cytokine levels (Interleukine-6, Tumor Necrosis Factor-α and Interleukine-10) in serum.

Other Outcome Measures

Postoperative outcome (composite measure of length of stay and complications) [Registration during admission, follow up 2 and 4 weeks after surgery]
Length of hospital stay and occurence of surgical site infection, abscess, urinary tract infection, pneumonia, anastomotic leakage, need for Intensive Care Unit admission, Systemic Inflammatory Response Syndrome, Multi Organ Failure, any adverse events.
Cognitive function [baseline, follow up 2 weeks after surgery]
Neuropsychological examination using a reading test, an auditory verbal learning test, WAIS III figure series and trail making tests.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.