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

February 4, 2022 updated by: Mack Mitchell, University of Texas Southwestern Medical Center
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University of Louisville
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Texas
      • Dallas, Texas, United States, 75390
        • U Texas Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo for Probiotic
Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.
Drug: Placebo for Probiotic
Capsule manufactured without active ingredients.
Other Names:
  • Dummy capsule
Active Comparator: Lactobacillus Rhamnosus GG
Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.
Dietary supplement: Lactobacillus Rhamnosus GG
Probiotic nutritional supplement; Lactobacillus Rhamnosus GG
Other Names:
  • Culturelle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MELD Score
Time Frame: 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.
30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MELD Score
Time Frame: 180 days
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
MELD Score
Time Frame: 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.
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Texas Southwestern Medical Center

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Cleveland Clinic
University of Massachusetts, Worcester
University of Louisville

Investigators

  • Principal Investigator: Mack C Mitchell, M.D., U Texas Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2013

Primary Completion (Actual)

July 1, 2018

Study Completion (Actual)

August 31, 2021

Study Registration Dates

First Submitted

August 12, 2013

First Submitted That Met QC Criteria

August 12, 2013

First Posted (Estimate)

August 14, 2013

Study Record Updates

Last Update Posted (Actual)

March 2, 2022

Last Update Submitted That Met QC Criteria

February 4, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU 092012-012
  • U01AA021893-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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