Anti-inflammatory Effects of Enriched Enteral Nutrition During Human Experimental Endotoxemia (VIHE)

The Effect of Enriched Enteral Nutrition on Inflammation and Sub-clinical Organ Dysfunction During Human Endotoxemia

During sepsis and septic shock the immune response can be overwhelming leading to excessive tissue damage, organ failure and death. Ideally, the inflammatory response is modulated leading to both adequate protection to invading pathogens as well as limitation of an exuberant immune response. In the last years, experimental evidence has been accumulating that enteral administration of lipid-enriched nutrition attenuates inflammation and preserves organ integrity in several inflammatory models. The current study investigates the immune-modulating potential of enriched enteral nutrition in a human setting of experimental endotoxemia.

Study Overview

• Status: Completed
• Conditions: Endotoxemia
• Intervention / Treatment: Other: control enteral nutrition; Other: enriched enteral feeding

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age ≥ 18 and ≤ 35 yrs
• Male
• Written informed consent
• non-smoking

Exclusion Criteria:

• Use of any medication (e.g. NSAID's, antibiotics, gastrointestinal motility altering medicine, corticosteroids)
• Smoking in the past year
• History, signs or symptoms of cardiovascular disease
• (Family; first degree) history of cerebrovascular disease
• Previous vagal collapse
• Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
• Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
• Renal impairment (defined as plasma creatinin >120 μmol/l)
• Liver enzyme abnormalities ( ASAT > 60 U/L, ALAT > 75 U/L, Gamma-GT > 60 U/L)
• Positive hepatitis serology
• Positive HIV test
• Allergy to milk and/or soy proteins

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: fasted control; Volunteers are fasted for 10 hours and subjected to experimental endotoxemia
Placebo Comparator: control feeding; Volunteers are fed a control nutrition starting 1 hour prior to LPS administration until 6 hours after LPS	Other: control enteral nutrition; This feeding consists of 20en% fat, 16en% protein and 49en% carbohydrates
Active Comparator: enriched feeding; volunteers receive the investigational feeding starting 1 hour prior to LPS administration until 6 hours after LPS	Other: enriched enteral feeding; This feeding contains 46 energy percent (en%) fat, 24en% protein and 30en% carbohydrates and is enriched with phospholipids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
circulating cytokines	several time points from LPS administration until 24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
markers for sub-clinical organ damage (kidney, endothelium, intestine)	several time points from LPS administration until 24 h

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Maastricht University Medical Center
• Investigators: Principal Investigator: Johannes Van der Hoeven, PhD, MD, Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center

Publications and helpful links

General Publications

• Lubbers T, Luyer MD, de Haan JJ, Hadfoune M, Buurman WA, Greve JW. Lipid-rich enteral nutrition reduces postoperative ileus in rats via activation of cholecystokinin-receptors. Ann Surg. 2009 Mar;249(3):481-7. doi: 10.1097/SLA.0b013e318194d187.
• Luyer MD, Greve JW, Hadfoune M, Jacobs JA, Dejong CH, Buurman WA. Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med. 2005 Oct 17;202(8):1023-9. doi: 10.1084/jem.20042397. Epub 2005 Oct 10.
• Luyer MD, Derikx JP, Beyaert R, Hadfoune M, van Kuppevelt TH, Dejong CH, Heineman E, Buurman WA, Greve JW. High-fat nutrition reduces hepatic damage following exposure to bacterial DNA and hemorrhagic shock. J Hepatol. 2009 Feb;50(2):342-50. doi: 10.1016/j.jhep.2008.08.025. Epub 2008 Nov 8.
• de Haan JJ, Lubbers T, Hadfoune M, Luyer MD, Dejong CH, Buurman WA, Greve JW. Postshock intervention with high-lipid enteral nutrition reduces inflammation and tissue damage. Ann Surg. 2008 Nov;248(5):842-8. doi: 10.1097/SLA.0b013e318188752c.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: April 7, 2010
• First Submitted That Met QC Criteria: April 8, 2010
• First Posted (Estimate): April 9, 2010

Study Record Updates

• Last Update Posted (Estimate): June 7, 2011
• Last Update Submitted That Met QC Criteria: June 6, 2011
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: enteral nutrition; innate immunity; endotoxemia; intestinal damage; nutritional anti-inflammatory pathway
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Bacteremia; Toxemia; Endotoxemia
• Other Study ID Numbers: 2009/168