Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function

Study Overview
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Brief Summary
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Gastric bypass surgery is the gold standard in bariatric surgery and is a successful method to reduce weight in morbidly obese subjects. Patients qualified for gastric bypass surgery are routinely pre-treated with a low calorie diet in order to reduce liver volume and to facilitate the approach of the gastro-oesophageal junction. Pre-treatment with omega-3 fatty acids has similar effects on liver volume, but a prospective comparison of both treatments has not been performed yet. Morbidly obese patients respond differently to surgical stress, due to a number of factors. First, obesity is associated with a low-grade inflammatory state induced by an increased amount of macrophages in adipose tissue. This state is associated with higher levels of pro-inflammatory cytokines in serum and with a less adequate immune response to infections. Second, obesity is associated with an altered cortisol metabolism possibly related to adrenal insufficiency. This could play an important role in the altered response to surgical stress and postoperative complications in obese subjects. Third, obesity is associated with altered erythrocyte function, including decreased erythrocyte deformability and increased aggregation, factors contributing to an impaired microcirculation. This study has a number of different aims. First, we will compare pre-treatment with the standard low calorie diet with omega-3 fatty acids on liver volume in patients qualified for gastric bypass surgery because of morbid obesity. Second, we will investigate the effect of omega-3 fatty acids on immune function, the low-inflammatory state of adipose tissue, the stress response of obese subjects before and erythrocyte function. Third, we will investigate the effect of gastric bypass surgery by comparing values before surgery with values on the first postoperative day and 6 months after surgery regarding to immunological parameters, stress response and erythrocyte function.

Official Title
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Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function

Conditions
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Morbid Obesity

Intervention / Treatment
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* Drug: Omega-3 fatty acid capsules
* Behavioral: Low calorie diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females undergoing laparoscopic gastric bypass surgery because of morbid obesity Age between 18 and 65 years Able to fit in the MRI Written informed consent Exclusion Criteria: Pregnancy Diabetes mellitus type 1 Current history of inflammatory, infectious or malignant disease Daily use of anti-inflammatory drugs Contra-indications for MRI imaging Contra-indications for the use of omega-3 fatty acids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low calorie diet<br>Low calorie diet 2 weeks pre-operatively | Behavioral: Low calorie diet<br>* A low calorie diet of 600 kcal/day during 2 weeks, using Modifast or an adjusted normal diet.<br>|
| Active Comparator: Omega-3 fatty acid capsules<br>2 times a day 1 capsule for 4 weeks before gastric bypass surgery | Drug: Omega-3 fatty acid capsules<br>* 2 times a day 1 capsule for 4 weeks before gastric bypass surgery<br>* Other names: docosahexaenoic acid (DHA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver volume | liver volume of the left hepatic lobe measured by MRI | baseline, after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peri-operative ex vivo LPS stimulated cytokine production capacity | IL-6, IL-10, TNF-alpha | baseline, operation day, postoperative day 1, follow up 6 months | 
| Macrophage infiltration in omentum fat biopsies |  | Biopsies during gastric bypass surgery | 
| Erythrocyte function | Measurement of erythrocyte deformability and aggregation with LORRCA (laser-assisted optical rotational red cell analyzer) | baseline, day of surgery, postoperative day 1, follow up 6 months | 
| Cortisol response | ACTH stimulation test | baseline, operation day, postoperative day 1, follow up 6 months | 
| Serum parameters of inflammatory response | IL-6, IL-10, TNF-alpha and C-reactive protein | baseline, operation day, postoperative day 1, follow up 6 months | 
| Assessment of the approach of the gastro-oesophageal junction | Surgeons fill out a questionnaire after the gastric bypass surgery | During gastric bypass surgery | 
| Patient satisfaction with intervention | Questionnaire | After the pre-operative treatment |