Clinical trial NCT01100996: Anti-inflammatory Effects of Enriched Enteral Nutrition During Human Experimental Endotoxemia
Official title: The Effect of Enriched Enteral Nutrition on Inflammation and Sub-clinical Organ Dysfunction During Human Endotoxemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Endotoxemia
Keywords: enteral nutrition
endotoxemia
innate immunity
nutritional anti-inflammatory pathway
intestinal damage
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Maastricht University Medical Center
First posted: 2010-04-09
Enrollment: 36
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: circulating cytokines
timeFrame: several time points from LPS administration until 24 hours
Secondary outcomes:
measure: markers for sub-clinical organ damage (kidney, endothelium, intestine)
timeFrame: several time points from LPS administration until 24 h
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center
name: Johannes Van der Hoeven, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.