The Effects of Ethanol on Gut Wall Integrity as Measured by I-FABP and LBP
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 15
- Locations
- 2
- Primary Endpoint
- The immediate effects of oral alcohol consumption in healthy volunteers on gut wall integrity as measured by I-FABP, LBP and IL-6.
Study Overview
Brief Summary
Objective: To determine the immediate effects of oral alcohol consumption in healthy volunteers on gut wall integrity as measured by I-FABP and LBP.
Study design: Randomized, single blinded cross over study.
Study population: 15 healthy adult male human volunteers will be included in this study.
Intervention: the consumption of alcoholic beverages (1 g/kg ethanol) of wine (12%) compared to the consumption of water.
Main study parameters/endpoints: The aim of this study is to determine the immediate effects of oral alcohol consumption in healthy volunteers on gut wall integrity as measured by I-FABP and LBP.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects consume 1g of alcohol per kg bodyweight. One blood sample of 14 ml followed by 6 samples of 8 ml will be drawn between 16.45 hours and 19:00 hours the day after. The first 6 observations take place in a single visit followed by one observation in short visit the next day. It is unlikely that subjects will experience any physical or psychological discomfort from the withdrawal of a total of 62 ml of blood in 24 hours or the consumption of the amounts alcohol or water mentioned above. The same protocol will be repeated one week after the first visit in which the alcohol group and water group are crossed over.
Detailed Description
A common finding in trauma patients admitted to the ER with serious injuries is the presence of alcohol abuse. Alcohol is involved in up to 40% of deaths from motor vehicle crashes, 60% of deaths from intentional injuries, and 50% of hospital admissions for injuries.
Chronic alcohol consumption leads to a decrease in gut wall integrity in actively drinking alcoholics and patients with alcohol induced liver disease. Animal studies show that the mucosal damage caused by alcohol consumption increases the permeability of the gut to macromolecules. This facilitates the translocation of endotoxin and other bacterial toxins from the gut lumen to the portal circulation. In addition to increased endotoxemia other studies show that the initial event in response to alcohol is an increased influx of leukocytes leading to an enhanced release of noxious mediators, such as reactive oxygen species, leukotrienes and histamine by mast cells. Alcohol consumption thus leads to a decrease in gut wall integrity with increased endotoxemia and as a result induces an inflammatory response. Data on the effects of acute alcohol consumption on gut wall integrity in non-alcoholics is still scarce.
In patients exposed to severe trauma, loss of gut wall integrity has been implicated as an important contributor to the development of excessive inflammation [6]. Intestinal mucosal damage develops early after trauma leading to loss of gut wall integrity and resulting in translocation of luminal bacteria and toxins into the gut wall. This has been associated with the development of an inflammatory response. This excessive inflammation can in turn lead to the systemic inflammatory response syndrome (SIRS) which can ultimately lead to multiple organ failure (MOF) and death. Up to 20% of the deaths in trauma patients are due to the consequences of SIRS and MOF.
When assessing the effects of alcohol and severe trauma on gut wall integrity combined with the fact that the two co-exist frequently one can hypothesize that the outcome for trauma patients under the influence of alcohol is detrimental. Literature regarding this issue is unequivocal, consisting only of relatively small retrospective series.
Population (base) 15 healthy adult male human volunteers will be included in this study
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Single (Investigator)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •male volunteers
- •age between 18 and 60 years
- •written informed consent
Exclusion Criteria
- •medical history of alcohol abuse
- •use of any medication
- •medical history of bowel disease
Outcomes
Primary Outcomes
The immediate effects of oral alcohol consumption in healthy volunteers on gut wall integrity as measured by I-FABP, LBP and IL-6.
Time Frame: The hours after consumption until 24 hours post-consumption
Secondary Outcomes
- The immediate effects of oral alcohol consumption in healthy volunteers on the hepatocyte as measured by L-FABP, AST, ALT and GGT.(The hours after consumption until 24 hours post-consumption.)
Investigators
JBF Hulscher
MD, PhD
University Medical Center Groningen