Alcohol and Innate Immunity

Completed

• Conditions: Binge Drinking
• Interventions: Other: Alcohol; Other: Glucose; Other: vehicle; Other: Fructose

• Registration Number: NCT02568904
• Lead Sponsor: Medical University of Graz

Brief Summary

Alcohol leads to a leaky gut and translocation of bacterial products. This may lead to inflammation and immune dysfunction as well as the typical hangover symptoms.

Detailed Description

Alcohol binge drinking, defined as 5 or more drinks for men and 4 or more drinks for women at one time, is the most frequent form of alcohol consumption worldwide, especially in younger people. This drinking pattern is popular and leads to increased mortality and morbidity. Therefore binge drinking is a major public health issue. The behavioural and neurological consequences of binge drinking are well characterized.

Less is known about the systemic effects on the gut as the first organ in contact with alcohol. Chronic alcohol intake can lead to increased gut permeability, bacterial translocation and alterations in the gut microbiome in animal models. Recently bacterial translocation has been shown in healthy volunteers after a single alcohol binge. On immune cells, acute alcohol intake seems to have dichotomous effects. On the one hand immunosuppressive and anti-inflammatory effects have been described, however, alcohol induced liver injury is driven by pro-inflammatory reactions. These immune effects seem to be driven by endotoxin or other bacterial products via Toll-like receptors that are translocated to the circulation via a defective gut barrier. Immune effects of alcohol have also been linked to hangover symptoms after an alcohol binge.

Furthermore there is evidence that endotoxemia might also contributes to alcohol dependence by promoting prolonged and increased voluntary alcohol intake in mice. On the other hand mutant mice lacking important genes for immune responses exhibit decreased alcohol consumption. This indicates that immune signaling promotes alcohol consumption. Therefore it is tempting to speculate that increased gut permeability leading to increased bacterial translocation after an acute alcohol binge could promote the desire for further alcohol consumption.

The investigators aim to test in this pilot trial whether one alcohol binge damages gut barrier function, increases bacterial translocation and causes innate immune dysfunction. Furthermore the effect of glucose and fructose will be studied too.

Study Timeline

• Study First Submitted: 2015-07-29
• Study First Submitted QC: 2015-10-05
• Study First Posted: 2015-10-06
• Study Start: 2016-12
• Primary Completion: 2019-02-22
• Study Completion: 2019-02-22
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-14
• Last Update Posted: 2020-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Participant is willing and able to give informed consent for participation in the study.
• Age above 18 years
• Willingness to abstain from alcohol 48h prior to the study visits

Exclusion Criteria

• Alcohol abuse .Alcohol Use Disorders Identification Test ≥ 8 in men or ≥ 7 in women or CAGE test ≥ 2 (both men and women)
• Elevated liver function test
• Any disease or medication that does not allow concomitant consumption of alcohol
• Women: pregnancy and lactation

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Alcohol binge	Alcohol	Healthy volunteers receive 2ml vodka 40% per kg bodyweight as a binge
Glucose	Glucose	75 g Glucose orally
Vehicle	vehicle	2ml tap water per kg body weight
Fructose	Fructose	75 g Fructose orally

Primary Outcome Measures

Name	Time	Method
Endotoxin assessed by percentage of endotoxin positive subjects	4 hours	Endotoxin measured by a HEK-blue cell based assay

Secondary Outcome Measures

Name	Time	Method
fibroblast growth factor 21 (FGF21)	4 hours	changes in FGF21 serum levels
gut permeability (zonulin in stool)	4 hours	changes in gut permeability
bacterial translocation (bacterial DNA in serum)	4 hours	changes in bacterial translocation
oxidative stress (advanced oxidation protein products)	4 hours	changes in oxidative stress
inflammation (neutrophil oxidative burst)	4 hours	changes in inflammation
neutrophil phagocytic capacity	4 hours	changes in neutrophil function
gut microbiome composition	4 hours	changes in gut microbiome composition

Trial Locations

Locations (1)

Department of Internal Medicine, Medical University of Graz; 🇦🇹 Graz, Austria