Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis (NTAH-Mod)

The University of Texas System (UT)

Status: Terminated

Conditions: Acute Alcoholic Hepatitis

Treatments: Dietary Supplement: Lactobacillus Rhamnosus GG; Drug: Placebo for Probiotic

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01922895

U01AA021893-01 (U.S. NIH Grant/Contract)

STU 092012-012

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 patients

Sex: All

Ages: 21 to 70 years old

Volunteers: No Healthy Volunteers

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.

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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45 participants in 2 patient groups, including a placebo group

Placebo for Probiotic

Placebo Comparator group

Description:

Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.

Treatment:

Drug: Placebo for Probiotic

Lactobacillus Rhamnosus GG

Active Comparator group

Description:

Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.

Treatment:

Dietary Supplement: Lactobacillus Rhamnosus GG