Alcohol, Gut Leakiness, & Liver Disease

NCT05428072 | Completed Early Phase 1 FDA Drug

• 1 other identifier: ORA 09042105
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to investigate the role of gut leakiness in alcoholic liver disease. Gut leakiness may be the missing susceptibility factor that explains why some alcoholics develop liver disease and others don't. For this study, subjects 480 (240 male, 240 female, ages 18-80) will be recruited. Alcoholic subjects will be recruited from outpatient \& inpatient alcohol detoxification units from Rush, Loyola \& two halfway houses (one for women, one for men); patients with liver disease from GI/Hepatology Services at Rush, Hines VA Hosp \& Loyola University; and controls from hospital staffs. All subjects will fill out a detailed questionnaire, be interviewed by the study coordinator \& undergo an exam by the PI to ensure that all inclusion criteria are satisfied. All subjects will have a urine collection for tests of intestinal permeability (urinary sugars). Gut leakiness will be determined by the amount of sugars in the urine.

Conditions

Alcoholic Liver Disease

Keywords

intestinal permeability

Outcome Measures

Primary Outcomes (2)

• Changes in gut permeability

  All participants will consume a sugar cocktail (lactulose \& mannitol) and collect their urine. A urinary analysis was performed to measure the secretion of sugar and indicates gut permeability.

  3 days

• Changes in gut permeability after consuming aspirin

  Participants will take will consume 2 doses of aspirin, 1.3 g each given at 12 \& 1 h before taking a sugar test. A urinary analysis was performed to measure the secretion of sugar and indicates gut permeability.

  1 day

Study Arms (1)

sugar test

EXPERIMENTAL

Participants will undergo 3 sugar tests followed by

Other: Sugar test; Drug: Aspirin Challenge

Interventions

Sugar test OTHER

All participants will take two sugar tests ( sugar cocktail consisting of mannitol \& lactulose) subjects within 2-3 days of the initial sugar test.

sugar test

Aspirin Challenge DRUG

All participants will take a sugar test after 2 doses of aspirin, 1.3 g each given at 12 \& 1 hour before the sugar drink.

sugar test

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• There are 4 different categories of participants that were used for recruitment:
• Healthy controls
• Subjects must have a normal physical exam
• No GI complaints
• No known liver disease
• Normal liver function tests (ALT, AST, bilirubin, alkaline phosphatase, serum albumin)
• Consume no more than a moderate amount of alcohol (NIAAA definition \[1 \]).
• These subjects should not be daily drinkers (\< 3x / week) and should typically drink \< 3 drinks per occasion.
• Alcoholics
• Subjects should fulfill NIAAA criteria for at-risk drinking \& alcohol abuse or dependence \& DSM-IV criteria for alcoholism
• Each must have consumed alcohol regularly for at least the past 3 mos but must be sober for 3-7 day post-binge at the time of sugar test (except for group 7)
• Have a total regular heavy drinking history of at least 10 y (except for Group 6) the minimal period of time required for the development of ALD.
• ALCOHOLICS WITHOUT LIVER DISEASE
• no clinical evidence of ALD on physical examination
• serum bilirubin or ALT or AST less than 1.25X normal

You may not qualify if:

• SOBER ALCOHOLICS WITH LD .
• Criteria is the same as Alcholics with liver disease but last drink was \>7 days from the study enrollment.
• Subjects with Non-alcoholic liver disease
• Criteria for LD are similar to those outlined for alcoholics with liver disease subjects except that drinking history should be similar to that of healthy volunteers. Subjects after liver transplant.
• These subjects must have successful liver transplantation at least 6 mos prior to the study and are on stable doses of immunosuppression for 3 mos.
• Unreliable drinking history (to rule out closet drinkers or pretenders).
• Subjects must clearly fulfill the criteria either of "alcoholism" or of "on-drinker".
• Subjects with a drinking history of 5-9 years duration are excluded since this period is not short enough to preclude cirrhosis nor long enough to cause ALD in most subjects.
• Significant renal impairment (creatinine\>l.2 mg/dL
• Diseases that affect GI motility such as scleroderma.
• insulin-requiring diabetes \&/or uncontrolled diabetes (Hgb-Alc\>8%)
• Clinically significant dehydration.
• clinically detectable ascites
• Significant peripheral edema
• Sepsis

Sponsors & Collaborators

• Rush University Medical Center: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Ali Keshavarzian

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Swanson GR, Garg K, Shaikh M, Keshavarzian A. Increased Intestinal Permeability and Decreased Resiliency of the Intestinal Barrier in Alcoholic Liver Disease. Clin Transl Gastroenterol. 2024 Apr 1;15(4):e00689. doi: 10.14309/ctg.0000000000000689.

  PMID: 38334953 DERIVED

MeSH Terms

Conditions

Liver Diseases, Alcoholic

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 16, 2022
• First Posted: June 22, 2022
• Study Start: January 1, 2003
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: June 22, 2022

Record last verified: 2022-06

Locations

US (1)