Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis

Acute Alcoholic Hepatitis Clinical Trial

— NTAH-Mod  

Official title:

Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01922895
• Other study ID #: STU 092012-012
• Secondary ID: U01AA021893-01
• Status: Terminated
• Phase: N/A
• Start date: August 1, 2013
• Est. completion date: August 31, 2021

Study information

• Verified date: February 2022
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 45
• Est. completion date: August 31, 2021
• Est. primary completion date: July 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Alcoholic Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Intervention

Dietary Supplement:
• Lactobacillus Rhamnosus GG
Probiotic nutritional supplement; Lactobacillus Rhamnosus GG

Drug:
• Placebo for Probiotic
Capsule manufactured without active ingredients.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	U Texas Southwestern Medical Center	Dallas	Texas
United States	University of Louisville	Louisville	Kentucky

Sponsors (5)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	National Institute on Alcohol Abuse and Alcoholism (NIAAA), The Cleveland Clinic, University of Louisville, University of Massachusetts, Worcester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MELD Score	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.	30 days
Secondary	MELD Score	Change in MELD scoring system over 180 day 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.	180 days
Secondary	MELD Score	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.	90 days