Clinical trial NCT01922895: Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
Official title: Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Alcoholic Hepatitis
Keywords: Alcoholic Hepatitis
MELD < 20
Probiotic
Nutritional Supplement
Lactobacillus Rhamnosus GG
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: The Cleveland Clinic
name: University of Massachusetts, Worcester
name: University of Louisville
First posted: 2013-08-14
Enrollment: 45
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: MELD Score
timeFrame: 30 days
Secondary outcomes:
measure: MELD Score
timeFrame: 180 days
measure: MELD Score
timeFrame: 90 days
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: U Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: U Texas Southwestern Medical Center
name: Mack C Mitchell, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vatsalya V, Cave MC, Kong M, Gobejishvili L, Falkner KC, Craycroft J, Mitchell M, Szabo G, McCullough A, Dasarathy S, Radaeva S, Barton B, McClain CJ. Keratin 18 Is a Diagnostic and Prognostic Factor for Acute Alcoholic Hepatitis. Clin Gastroenterol Hepatol. 2020 Aug;18(9):2046-2054. doi: 10.1016/j.cgh.2019.11.050. Epub 2019 Dec 4.