Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis

Not Applicable

Terminated

• Conditions: Acute Alcoholic Hepatitis
• Interventions: Drug: Placebo for Probiotic; Dietary Supplement: Lactobacillus Rhamnosus GG

• Registration Number: NCT01922895
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

This study is being done to find out whether a diet supplemented with a probiotic nutrient can improve alcoholic hepatitis and gut complications compared to routine standard care.

Detailed Description

Aim 1: Evaluate the effects of probiotic supplements on improvement in MELD score and gut mucosal integrity in patients with MELD \< 21. Patients will be randomized to receive daily probiotics for 6 months and standard of care treatment or placebo with standard care.

Aim 2: Document the natural history of moderately severe alcoholic hepatitis. Patients who decline randomization will be offered the option of inclusion in the study prospectively for data collection purposes and research study procedures.

Aim 3: Create a data and tissue biorepository. This biorepository will serve as a national resource for studies related to acute alcoholic hepatitis.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2013-08-01
• Study First Submitted: 2013-08-12
• Study First Submitted QC: 2013-08-12
• Study First Posted: 2013-08-14
• Primary Completion: 2018-07-01
• Study Completion: 2021-08-31
• Results First Submitted: 2022-01-09
• Status Verified: 2022-02
• Results First Submitted QC: 2022-02-04
• Last Update Submitted: 2022-02-04
• Results First Posted: 2022-03-02
• Last Update Posted: 2022-03-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Ability to provide informed consent by subject or appropriate family member
2. Age between 21-70 years
3. Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before enrollment
4. At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain, jaundice, leukocytosis, hepatomegaly AND
5. Elevation of AST > 80 U/L, but < 500 U/L at the time of admission or within 3 days of baseline visit; AST > ALT and ALT < 200 U/L; total bilirubin > 3 mg/dL AND
6. Liver biopsy showing alcoholic hepatitis (steatohepatitis) OR ultrasound of liver showing increased echogenicity OR CT scan showing decreased attenuation of liver compared to spleen OR MRI showing fatty liver (decreased signaling intensity on T1 weighted images). If the liver biopsy (done within 60 days of inclusion) confirms diagnosis of AAH then inclusion e will be waived.
7. Model for End-Stage Liver Disease (MELD) <20
8. Willingness to utilize two reliable forms of contraception (both males and females of childbearing potential) from screening through the first six weeks of study.

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Exclusion Criteria

1. Hypotension with BP < 80/50 after volume repletion
2. Pregnancy; incarceration; inability to provide consent or lack of appropriate family member
3. Signs of systemic infection: Fever > 38o C and positive blood or ascites cultures on appropriate antibiotic therapy for > 3 days within 3 days of inclusion
4. Acute gastrointestinal bleeding requiring > 2 units blood transfusion within the previous 4 days
5. Undue risk from immunosuppression: Positive HBsAg; a positive skin PPD skin test or history of treatment for tuberculosis; history of any malignancy including hepatocellular carcinoma; known HIV infection
6. Treatment with corticosteroids or other immunosuppressive medications including specific anti-TNF therapy (not including pentoxifylline), calcineurin inhibitors for > 3 days within the previous 3 months.
7. Evidence of acute pancreatitis: CT evidence and/or amylase or lipase > 5 X upper limit of normal
8. Serious cardiac, respiratory or neurologic disease or evidence of autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilsons disease, hemochromatosis, secondary iron overload due to chronic hemolysis, alpha-1-antitrypsin deficiency
9. Acute or chronic kidney injury with serum creatinine > 3.0 mg/dl

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo for Probiotic	Placebo for Probiotic	Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.
Lactobacillus Rhamnosus GG	Lactobacillus Rhamnosus GG	Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.

Primary Outcome Measures

Name	Time	Method
MELD Score	30 days	Change in MELD scoring system for assessing the severity of chronic liver disease; MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8\[Ln serum bilirubin (mg/dL)\] + 11.2\[Ln INR\] + 9.6\[Ln serum creatinine (mg/dL)\] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome.

Secondary Outcome Measures

Name	Time	Method
MELD Score	90 days	Change in MELD scoring system at 90 days study duration. MELD (Model of End Stage Liver Disease) scoring system for assessing the severity of chronic liver disease; calculated from serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) MELD = 3.8\[Ln serum bilirubin (mg/dL)\] + 11.2\[Ln INR\] + 9.6\[Ln serum creatinine (mg/dL)\] + 6.4. MELD score range from 6-40 with higher scores indicating more severe liver disease and a worse outcome.

Trial Locations

Locations (3)

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

U Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States