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

NCT01100996 | Completed DMC

• 1 other identifier: 2009/168
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Endotoxemia

Keywords

enteral nutrition; endotoxemia; innate immunity; nutritional anti-inflammatory pathway; intestinal damage

Outcome Measures

Primary Outcomes (1)

• circulating cytokines

  several time points from LPS administration until 24 hours

Secondary Outcomes (1)

• markers for sub-clinical organ damage (kidney, endothelium, intestine)

  several time points from LPS administration until 24 h

Study Arms (3)

fasted control

NO INTERVENTION

Volunteers are fasted for 10 hours and subjected to experimental endotoxemia

control feeding

PLACEBO COMPARATOR

Volunteers are fed a control nutrition starting 1 hour prior to LPS administration until 6 hours after LPS

Other: control enteral nutrition

enriched feeding

ACTIVE COMPARATOR

volunteers receive the investigational feeding starting 1 hour prior to LPS administration until 6 hours after LPS

Other: enriched enteral feeding

Interventions

control enteral nutrition OTHER

This feeding consists of 20en% fat, 16en% protein and 49en% carbohydrates

control feeding

enriched enteral feeding OTHER

This feeding contains 46 energy percent (en%) fat, 24en% protein and 30en% carbohydrates and is enriched with phospholipids.

enriched feeding

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Maastricht University Medical Center: collaborator

Study Sites (1)

Radboud University Medical Center

Nijmegen, 6525 GA, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 16216887 BACKGROUND

• 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.

  PMID: 19070388 BACKGROUND

• 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.

  PMID: 18948813 BACKGROUND

• 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.

  PMID: 19247038 BACKGROUND

MeSH Terms

Conditions

Endotoxemia

Condition Hierarchy (Ancestors)

Bacteremia; Sepsis; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Johannes Van der Hoeven, PhD, MD

  Department of Intensive Care Medicine, Radboud University Nijmegen Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 7, 2010
• First Posted: April 9, 2010
• Study Start: February 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: April 1, 2011
• Last Updated: June 7, 2011

Record last verified: 2010-02

Locations

NL (1)