Alcohol and Innate Immunity

Binge Drinking Clinical Trial

Official title:

The Effects of Binge Drinking on Innate Host Defence Mechanisms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02568904
• Other study ID #: Alcohol01
• Status: Completed
• Start date: December 2016
• Est. completion date: February 22, 2019

Study information

• Verified date: May 2020
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: February 22, 2019
• Est. primary completion date: February 22, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Binge Drinking

Intervention

Other:
• Alcohol
every participant will drink vodka at a dose of 2ml/kg bodyweight
• Glucose
oral Glucose tolerance test
• Fructose
oral fructose tolerance test
• vehicle
control (water)

Locations

Country	Name	City	State
Austria	Department of Internal Medicine, Medical University of Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endotoxin assessed by percentage of endotoxin positive subjects	Endotoxin measured by a HEK-blue cell based assay	4 hours
Secondary	gut permeability (zonulin in stool)	changes in gut permeability	4 hours
Secondary	bacterial translocation (bacterial DNA in serum)	changes in bacterial translocation	4 hours
Secondary	oxidative stress (advanced oxidation protein products)	changes in oxidative stress	4 hours
Secondary	inflammation (neutrophil oxidative burst)	changes in inflammation	4 hours
Secondary	neutrophil phagocytic capacity	changes in neutrophil function	4 hours
Secondary	gut microbiome composition	changes in gut microbiome composition	4 hours
Secondary	fibroblast growth factor 21 (FGF21)	changes in FGF21 serum levels	4 hours