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

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ClinicalTrials.gov Identifier: NCT01922895
Recruitment Status : Recruiting
First Posted : August 14, 2013
Last Update Posted : May 12, 2017
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment
Acute Alcoholic Hepatitis Dietary Supplement: Lactobacillus Rhamnosus GG Drug: Placebo for Probiotic

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Official Title: Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
Study Start Date : October 2013
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

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 Name: 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 Name: Culturelle

Outcome Measures

Primary Outcome Measures :
  1. MELD score [ Time Frame: 30 days ]
    MELD scoring system for assessing the severity of chronic liver disease; MELD = 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4.

Secondary Outcome Measures :
  1. MELD score [ Time Frame: 180 days ]
    Improvement in MELD score over 180 day study duration.

Other Outcome Measures:
  1. Gut mucosal permeability [ Time Frame: 180 days ]
    Gut mucosal permeability will be measured by changes from baseline in the gut mucosal integrity as assessed by the lactulose/mannitol test.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01922895

Contact: Mack C Mitchell, M.D. 214-645-8300 Mack.Mitchell@UTSouthwestern.edu
Contact: Blair Holbein, PhD 214-648-5009 Blair.Holbein@UTSouthwestern.edu

United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Craig J McClain, MD    502-852-6991      
Principal Investigator: Craig J McClain, MD         
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Arthur J McCullough, MD    216-444-2766      
Principal Investigator: Arthur J McCullough, MD         
United States, Texas
U Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Mack C Mitchell, M.D.    214-645-8300    Mack.Mitchell@UTSouthwestern.edu   
Principal Investigator: Mack C Mitchell, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Cleveland Clinic
University of Massachusetts, Worcester
University of Louisville
Principal Investigator: Mack C Mitchell, M.D. U Texas Southwestern Medical Center
More Information

Responsible Party: Mack Mitchell, Professor, Vice-Chair Internal Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01922895     History of Changes
Other Study ID Numbers: UTSW_092012-012
U01AA021893-01 ( U.S. NIH Grant/Contract )
First Posted: August 14, 2013    Key Record Dates
Last Update Posted: May 12, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Mack Mitchell, University of Texas Southwestern Medical Center:
Alcoholic Hepatitis
MELD < 20
Nutritional Supplement
Lactobacillus Rhamnosus GG

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders