Effect of Probiotics on Gut-Liver Axis of Alcoholic Liver Disease (EPALD)

Background/Aims:

The investigators explored the therapeutic effects of probiotics in patients with AH.

Methods:

Between September 2010 and April 2012, the investigators conducted a 7-day, double-controlled, randomized, prospective clinical trial comparing the efficacy of probiotics in improving liver enzymes, LPS, pro-inflammatory cytokines. AH was defined as an aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 and elevated AST (ALT) level with an alcohol consumption history within 48 hours. Patients were randomized to receive 7 days of probiotics (1500 mg/day) or placebo. The levels of liver enzymes, modified Discriminant Function (mDF), LPS, and pro-inflammatory cytokines were checked at baseline and again after therapy.

Study Overview

• Status: Completed
• Conditions: Alcoholic Liver Disease
• Intervention / Treatment: Drug: alcohol, hepatitis, Placebo; Drug: hepatitis, alcohol, probiotics

Detailed Description

Background/Aims: Alcoholic hepatitis (AH) is one of the leading causes of liver diseases. Gut-derived microbial lipopolysaccharide (LPS) has been known as a central role in the pathogenesis of AH. Some animal studies suggested an emerging role of probiotics in restoration of the bowel flora and improving liver enzymes. We explored the therapeutic effects of probiotics in patients with AH.

Methods: Between September 2010 and April 2012, we conducted a 7-day, double-controlled, randomized, prospective clinical trial comparing the efficacy of probiotics in improving liver enzymes, LPS, pro-inflammatory cytokines. AH was defined as an aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 and elevated AST (ALT) level with an alcohol consumption history within 48 hours. Patients were randomized to receive 7 days of probiotics (1500 mg/day) or placebo. The levels of liver enzymes, modified Discriminant Function (mDF), LPS, and pro-inflammatory cytokines were checked at baseline and again after therapy.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chuncheon, Korea, Republic of, 200-704
    • Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Alcoholic Hepatitis

Exclusion Criteria:

• Cancer
• Viral Hepatitis, other Hepatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: alcohol, hepatitis, Placebo; We explored the therapeutic effects of probiotics in patients with alcoholic hepatitis	Drug: alcohol, hepatitis, Placebo; Placebos of the same shape and size were manufactured at Pharmaceutical Corporation.; Other Names: Placebo
Active Comparator: hepatitis, alcohol, probiotics; We explored the therapeutic effects of probiotics in patients with alcoholic hepatitis	Drug: hepatitis, alcohol, probiotics; 7 days of probiotics (1500 mg/day); Other Names: LACTOWELL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Enzymes(ALT)	Blood analysis was performed using standard methodologies.	7 days after probiotics

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipopolysaccharide (LPS) and Pro-inflammatory Cytokines	For the measurements of cytokines, homogenates of serum were processed with Human Tumor necrosis factor-alpha ELISA Kit and Human interleukin 1 beta ELISA Kit . For the measurement of LPS ELISA Kit was used. Assays were performed according to the manufacturer's instructions.	7 days after probiotics

Collaborators and Investigators

• Sponsor: Chuncheon Sacred Heart Hospital
• Investigators: Principal Investigator: Ki Tae Suk, PhD, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital

Publications and helpful links

General Publications

• Han SH, Suk KT, Kim DJ, Kim MY, Baik SK, Kim YD, Cheon GJ, Choi DH, Ham YL, Shin DH, Kim EJ. Effects of probiotics (cultured Lactobacillus subtilis/Streptococcus faecium) in the treatment of alcoholic hepatitis: randomized-controlled multicenter study. Eur J Gastroenterol Hepatol. 2015 Nov;27(11):1300-6. doi: 10.1097/MEG.0000000000000458.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: December 27, 2011
• First Submitted That Met QC Criteria: December 28, 2011
• First Posted (Estimate): December 29, 2011

Study Record Updates

• Last Update Posted (Estimate): April 14, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: hepatitis, alcohol
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol-Induced Disorders; Liver Diseases; Liver Diseases, Alcoholic; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: EPALD