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

Primary Purpose

Acute Alcoholic Hepatitis

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Lactobacillus Rhamnosus GG
Placebo for Probiotic
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Acute Alcoholic Hepatitis focused on measuring Alcoholic Hepatitis, MELD < 20, Probiotic, Nutritional Supplement, Lactobacillus Rhamnosus GG

Eligibility Criteria

21 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University of Louisville
  • Cleveland Clinic
  • U Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo for Probiotic

Lactobacillus Rhamnosus GG

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
August 12, 2013
Last Updated
February 4, 2022
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
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1. Study Identification

Unique Protocol Identification Number
NCT01922895
Brief Title
Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
Acronym
NTAH-Mod
Official Title
Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Why Stopped
Lack of funding
Study Start Date
August 1, 2013 (Actual)
Primary Completion Date
July 1, 2018 (Actual)
Study Completion Date
August 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the 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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Alcoholic Hepatitis
Keywords
Alcoholic Hepatitis, MELD < 20, Probiotic, Nutritional Supplement, Lactobacillus Rhamnosus GG

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo for Probiotic
Arm Type
Placebo Comparator
Arm Description
Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.
Arm Title
Lactobacillus Rhamnosus GG
Arm Type
Active Comparator
Arm Description
Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.
Intervention Type
Dietary Supplement
Intervention Name(s)
Lactobacillus Rhamnosus GG
Other Intervention Name(s)
Culturelle
Intervention Description
Probiotic nutritional supplement; Lactobacillus Rhamnosus GG
Intervention Type
Drug
Intervention Name(s)
Placebo for Probiotic
Other Intervention Name(s)
Dummy capsule
Intervention Description
Capsule manufactured without active ingredients.
Primary Outcome Measure Information:
Title
MELD Score
Description
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.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
MELD Score
Description
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.
Time Frame
180 days
Title
MELD Score
Description
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.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to provide informed consent by subject or appropriate family member Age between 21-70 years Recent alcohol consumption > 50 g/d for > 6 months, continuing within two months before enrollment At least 2 of the following symptoms or signs of acute alcoholic hepatitis: Anorexia, nausea, RUQ pain, jaundice, leukocytosis, hepatomegaly AND 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 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. Model for End-Stage Liver Disease (MELD) <20 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: Hypotension with BP < 80/50 after volume repletion Pregnancy; incarceration; inability to provide consent or lack of appropriate family member 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 Acute gastrointestinal bleeding requiring > 2 units blood transfusion within the previous 4 days 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 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. Evidence of acute pancreatitis: CT evidence and/or amylase or lipase > 5 X upper limit of normal 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 Acute or chronic kidney injury with serum creatinine > 3.0 mg/dl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mack C Mitchell, M.D.
Organizational Affiliation
U Texas Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
U Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31811953
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.
Results Reference
derived

Learn more about this trial

Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis

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