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

Study Overview
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Brief Summary
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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.

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

Conditions
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Endotoxemia

Intervention / Treatment
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* Other: control enteral nutrition
* Other: enriched enteral feeding


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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enteral nutrition, endotoxemia, innate immunity, nutritional anti-inflammatory pathway, intestinal damage