Effects of Ethanol on Intestinal Permeability and Integrity

The Effect of Ethanol on Intestinal Permeability and Integrity in Healthy Individuals

Alcohol consumption is a major health problem worldwide. It affects all systems of the body especially the gastrointestinal tract. Acute or chronic alcohol consumption has deleterious effects on the gastrointestinal mucosa vary from increased intestinal permeability, structural changes to sever destruction of the epithelial lining cells. Human data are still limited and most of the studies were performed in chronic alcohol abusers.

The investigators hypothesize that moderate alcohol drinking also may increase small intestinal permeability and contribute to the subsequent disruption of the tight junction complex. This study may provide more insight into the effects of moderate alcohol drinking on the small intestinal permeability.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Device: Gastroduodenoscopy- Intraduodenal intubation

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6202 AZ
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed informed consent form.
• Male gender to avoid the gender-related differences in ethanol metabolism.
• Between 18-45 years to avoid age-related changes in ethanol metabolism39.
• Normal medical history and physical examination.
• Normal liver function tests (i.e. ALT, AST, and γGT) according to the reference values for normal ranges of the liver enzymes at the laboratory of clinical chemistry of the Maastricht University Medical Center.
• Caucasian ethnicity.
• BMI=18 - 30 kg/m2.

Exclusion Criteria:

• History of gastro-intestinal disorders or abdominal surgery.
• History of alcohol abuse or current excessive alcohol consumption (> 2 alcoholic beverages per day or > 14 alcoholic beverages per week)40.
• Recent or chronic medications that may interact with ethanol metabolism or intestinal permeability i.e., NSAIDs, benzodiazepines and antidepressants.
• Smoking.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: alcohol; Intraduodenal infusion of ethanol	Device: Gastroduodenoscopy- Intraduodenal intubation; 20 g ethanol diluted up to 10% in tap water
Other: Ethanol	Device: Gastroduodenoscopy- Intraduodenal intubation; 20 g ethanol diluted up to 10% in tap water
Experimental: Placebo; Intraduodenal infusion of tap water	Device: Gastroduodenoscopy- Intraduodenal intubation; 20 g ethanol diluted up to 10% in tap water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess intestinal permeability by means of sugar permeability testing after intraduodenal administration of ethanol.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess tight junctions structure and proteins in biopsy specimens after intraduodenal administration of ethanol.	2 years

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Top Institute Food and Nutrition
• Investigators: Principal Investigator: A Masclee, MD PhD, Maastricht UMC

Publications and helpful links

General Publications

• Draper LR, Gyure LA, Hall JG, Robertson D. Effect of alcohol on the integrity of the intestinal epithelium. Gut. 1983 May;24(5):399-404. doi: 10.1136/gut.24.5.399.
• Hirsch S, Chaves G, Gotteland M, de la Maza P, Petermann M, Barrera P, Bunout D. [Intestinal permeability in alcoholic patients without liver damage]. Rev Med Chil. 1997 Jun;125(6):653-8. Spanish.
• Basuroy S, Sheth P, Mansbach CM, Rao RK. Acetaldehyde disrupts tight junctions and adherens junctions in human colonic mucosa: protection by EGF and L-glutamine. Am J Physiol Gastrointest Liver Physiol. 2005 Aug;289(2):G367-75. doi: 10.1152/ajpgi.00464.2004. Epub 2005 Feb 17.
• Elamin E, Masclee A, Troost F, Pieters HJ, Keszthelyi D, Aleksa K, Dekker J, Jonkers D. Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach. PLoS One. 2014 Sep 16;9(9):e107421. doi: 10.1371/journal.pone.0107421. eCollection 2014.

Helpful Links

• Increased intestinal permeability

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: June 25, 2009
• First Submitted That Met QC Criteria: June 25, 2009
• First Posted (Estimate): June 26, 2009

Study Record Updates

• Last Update Posted (Estimate): November 13, 2014
• Last Update Submitted That Met QC Criteria: November 11, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: cytokines; inflammatory bowel diseases; Permeability; tight junctions; The effect of alcohol on the intestinal permeability may have major consequences on health.; It's generally accepted that an increased intestinal permeability in alcoholic subjects lead; to translocation of bacterial endotoxins from the gut lumen into the portal vein and then to the liver.; In the liver, endotoxins trigger the immune system and activate the resident macrophages, Kupffer cells.; Activation of Kupffer cells leads to production of chemokines (IL-8) and; proinflammatory cytokines (IL-1, TNFα),resulting in hepatocytes damage, inflammation, fibrosis and finally cirrhosis.
• Other Study ID Numbers: 09-3-026