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Alcohol and Innate Immunity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02568904
Recruitment Status : Completed
First Posted : October 6, 2015
Last Update Posted : May 15, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment
Binge Drinking Other: Alcohol Other: Glucose Other: Fructose Other: vehicle

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.

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Study Type : Observational
Actual Enrollment : 46 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: The Effects of Binge Drinking on Innate Host Defence Mechanisms
Actual Study Start Date : December 2016
Actual Primary Completion Date : February 22, 2019
Actual Study Completion Date : February 22, 2019

Group/Cohort Intervention/treatment
Alcohol binge
Healthy volunteers receive 2ml vodka 40% per kg bodyweight as a binge
Other: Alcohol
every participant will drink vodka at a dose of 2ml/kg bodyweight

Fructose
75 g Fructose orally
Other: Fructose
oral fructose tolerance test

Glucose
75 g Glucose orally
Other: Glucose
oral Glucose tolerance test

Vehicle
2ml tap water per kg body weight
Other: vehicle
control (water)




Primary Outcome Measures :
  1. Endotoxin assessed by percentage of endotoxin positive subjects [ Time Frame: 4 hours ]
    Endotoxin measured by a HEK-blue cell based assay


Secondary Outcome Measures :
  1. gut permeability (zonulin in stool) [ Time Frame: 4 hours ]
    changes in gut permeability

  2. bacterial translocation (bacterial DNA in serum) [ Time Frame: 4 hours ]
    changes in bacterial translocation

  3. oxidative stress (advanced oxidation protein products) [ Time Frame: 4 hours ]
    changes in oxidative stress

  4. inflammation (neutrophil oxidative burst) [ Time Frame: 4 hours ]
    changes in inflammation

  5. neutrophil phagocytic capacity [ Time Frame: 4 hours ]
    changes in neutrophil function

  6. gut microbiome composition [ Time Frame: 4 hours ]
    changes in gut microbiome composition

  7. fibroblast growth factor 21 (FGF21) [ Time Frame: 4 hours ]
    changes in FGF21 serum levels


Biospecimen Retention:   Samples Without DNA
Serum, Plasma, Urine, Stool


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
Healthy volunteers selected from a database
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02568904


Locations
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Austria
Department of Internal Medicine, Medical University of Graz
Graz, Austria, 8010
Sponsors and Collaborators
Medical University of Graz
Investigators
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Principal Investigator: Vanessa Stadlbauer, MD Medical University of Graz
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Responsible Party: Medical University of Graz
ClinicalTrials.gov Identifier: NCT02568904    
Other Study ID Numbers: Alcohol01
First Posted: October 6, 2015    Key Record Dates
Last Update Posted: May 15, 2020
Last Verified: May 2020
Additional relevant MeSH terms:
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Binge Drinking
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Alcohol Drinking
Drinking Behavior
Mental Disorders