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Alcohol, Gut Leakiness, & Liver Disease

Primary Purpose

Alcoholic Liver Disease

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sugar test
Aspirin Challenge
Sponsored by
Rush University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Alcoholic Liver Disease focused on measuring intestinal permeability

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

These are the different alcoholic groups and their specific inclusion criteria:

ALCOHOLICS WITHOUT LIVER DISEASE

  • no clinical evidence of ALD on physical examination
  • serum bilirubin or ALT or AST less than 1.25X normal
  • sobriety must be <7 days at the time of sugar test.

ALCOHOLICS WITH LIVER DISEASE

  • These subjects will have 1 of 3 possible grades of LD severity (mild, moderate, severe) & have either clinical evidence of LD (hepatomegaly, splenomegaly, and esophageal varices), or serum bilirubin or ALT or AST more than 1.5X normal.
  • If liver biopsy or CT or ultrasound is available, there should be histological evidence of LD (alcoholic hepatitis or cirrhosis) or radiological evidence of LD (cirrhotic liver, splenomegaly, varices)
  • Their sobriety must be <7 days at the time of the sugar test.

ALCOHOLICS WITH SHORT-TERM Drinking

  • These subjects should fulfill the criteria of alcohol abuse
  • have sobriety <7 days at the time of urine collection, but the duration of their heavy drinking must be <5 years
  • They must not have any liver disease (negative serology) due to non-EtOH causes or clinical evidence of
  • cirrhosis. Here, liver enzyme levels are not inclusion/exclusion criteria; but since the duration of EtOH abuse (<5 y) is too short for the development of cirrhosis, it is expected that none will have sustained elevated liver enzymes.

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.

Exclusion Criteria:

  • 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
  • Clinically significant cardiac failure
  • Regular daily use of medications that may affect intestinal permeability such as NSAIDS or intestinal motility (e.g. metoclopramide).
  • Alcoholics positive for other markers of LD such as smooth muscle antibody, hepatitis B surface antigen, hepatitis C antibody or hemochromatosis
  • Inability to sign an informed consent form
  • Patients with low platelet count (<80k), uncorrectable prolonged PT (>15 sec), history of bleeding will be excluded from aspirin tests

Sites / Locations

  • Ali Keshavarzian

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

sugar test

Arm Description

Participants will undergo 3 sugar tests followed by

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
June 16, 2022
Last Updated
June 16, 2022
Sponsor
Rush University Medical Center
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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1. Study Identification

Unique Protocol Identification Number
NCT05428072
Brief Title
Alcohol, Gut Leakiness, & Liver Disease
Official Title
Alcohol, Gut Leakiness, & Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
January 2003 (Actual)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rush University Medical Center
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Liver Disease
Keywords
intestinal permeability

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
195 (Actual)

8. Arms, Groups, and Interventions

Arm Title
sugar test
Arm Type
Experimental
Arm Description
Participants will undergo 3 sugar tests followed by
Intervention Type
Other
Intervention Name(s)
Sugar test
Intervention Description
All participants will take two sugar tests ( sugar cocktail consisting of mannitol & lactulose) subjects within 2-3 days of the initial sugar test.
Intervention Type
Drug
Intervention Name(s)
Aspirin Challenge
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in gut permeability
Description
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.
Time Frame
3 days
Title
Changes in gut permeability after consuming aspirin
Description
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.
Time Frame
1 day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. These are the different alcoholic groups and their specific inclusion criteria: ALCOHOLICS WITHOUT LIVER DISEASE no clinical evidence of ALD on physical examination serum bilirubin or ALT or AST less than 1.25X normal sobriety must be <7 days at the time of sugar test. ALCOHOLICS WITH LIVER DISEASE These subjects will have 1 of 3 possible grades of LD severity (mild, moderate, severe) & have either clinical evidence of LD (hepatomegaly, splenomegaly, and esophageal varices), or serum bilirubin or ALT or AST more than 1.5X normal. If liver biopsy or CT or ultrasound is available, there should be histological evidence of LD (alcoholic hepatitis or cirrhosis) or radiological evidence of LD (cirrhotic liver, splenomegaly, varices) Their sobriety must be <7 days at the time of the sugar test. ALCOHOLICS WITH SHORT-TERM Drinking These subjects should fulfill the criteria of alcohol abuse have sobriety <7 days at the time of urine collection, but the duration of their heavy drinking must be <5 years They must not have any liver disease (negative serology) due to non-EtOH causes or clinical evidence of cirrhosis. Here, liver enzyme levels are not inclusion/exclusion criteria; but since the duration of EtOH abuse (<5 y) is too short for the development of cirrhosis, it is expected that none will have sustained elevated liver enzymes. 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. Exclusion Criteria: 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 Clinically significant cardiac failure Regular daily use of medications that may affect intestinal permeability such as NSAIDS or intestinal motility (e.g. metoclopramide). Alcoholics positive for other markers of LD such as smooth muscle antibody, hepatitis B surface antigen, hepatitis C antibody or hemochromatosis Inability to sign an informed consent form Patients with low platelet count (<80k), uncorrectable prolonged PT (>15 sec), history of bleeding will be excluded from aspirin tests
Facility Information:
Facility Name
Ali Keshavarzian
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States

12. IPD Sharing Statement

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Alcohol, Gut Leakiness, & Liver Disease

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