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

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.

Study Overview

• Status: Completed
• Conditions: Morbid Obesity
• Intervention / Treatment: Behavioral: Low calorie diet; Drug: Omega-3 fatty acid capsules

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Noord Holland
    • Beverwijk, Noord Holland, Netherlands, 1942 LE
      • Rode Kruis Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low calorie diet; Low calorie diet 2 weeks pre-operatively	Behavioral: Low calorie diet; A low calorie diet of 600 kcal/day during 2 weeks, using Modifast or an adjusted normal diet.
Active Comparator: Omega-3 fatty acid capsules; 2 times a day 1 capsule for 4 weeks before gastric bypass surgery	Drug: Omega-3 fatty acid capsules; 2 times a day 1 capsule for 4 weeks before gastric bypass surgery; Other Names: docosahexaenoic acid (DHA); omega-3 fatty acids; purified fish oil; eicosapentoenoic acid (EPA)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medical Center Alkmaar
• Investigators: Principal Investigator: A.P.J. Houdijk, Dr., Rode Kruis Ziekenhuis, Medisch Centrum Alkmaar

Publications and helpful links

General Publications

• Bakker N, van den Helder RS, Geenen RWF, Hunfeld MA, Cense HA, Demirkiran A, Houdijk APJ. Four Weeks of Preoperative Omega-3 Fatty Acids Reduce Liver Volume: a Randomised Controlled Trial. Obes Surg. 2019 Jul;29(7):2037-2044. doi: 10.1007/s11695-019-03814-7.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: July 29, 2014
• First Submitted That Met QC Criteria: July 31, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 28, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid
• Other Study ID Numbers: NL47021.029.13