Effects of Ethanol on Intestinal Permeability and Integrity

NCT00928733 | Completed DMC

• 1 other identifier: 09-3-026
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Permeability; tight junctions; cytokines; inflammatory bowel diseases; 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.

Outcome Measures

Primary Outcomes (1)

• To assess intestinal permeability by means of sugar permeability testing after intraduodenal administration of ethanol.

  2 years

Secondary Outcomes (1)

• To assess tight junctions structure and proteins in biopsy specimens after intraduodenal administration of ethanol.

  2 years

Study Arms (3)

alcohol

EXPERIMENTAL

Intraduodenal infusion of ethanol

Device: Gastroduodenoscopy- Intraduodenal intubation

Ethanol

OTHER

Device: Gastroduodenoscopy- Intraduodenal intubation

Placebo

EXPERIMENTAL

Intraduodenal infusion of tap water

Device: Gastroduodenoscopy- Intraduodenal intubation

Interventions

Gastroduodenoscopy- Intraduodenal intubation DEVICE

20 g ethanol diluted up to 10% in tap water

Ethanol; Placebo; alcohol

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Top Institute Food and Nutrition: collaborator

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, 6202 AZ, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 6840613 BACKGROUND

• 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.

  PMID: 9515283 BACKGROUND

• 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.

  PMID: 15718285 BACKGROUND

• 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.

  PMID: 25226407 RESULT

Related Links

• Increased intestinal permeability

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Inflammation; Fibrosis

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• A Masclee, MD PhD

  Maastricht UMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2009
• First Posted: June 26, 2009
• Study Start: September 1, 2009
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: November 13, 2014

Record last verified: 2014-11

Locations

NL (1)