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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Texas Southwestern Medical Center
Sponsor:
Collaborators:
The Cleveland Clinic
University of Massachusetts, Worcester
University of Louisville
Information provided by (Responsible Party):
Mack Mitchell, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01922895
First received: August 12, 2013
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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 Intervention
Acute Alcoholic Hepatitis
Dietary Supplement: Lactobacillus Rhamnosus GG
Drug: Placebo for Probiotic

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • MELD score [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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:
  • MELD score [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
    Improvement in MELD score over 180 day study duration.


Other Outcome Measures:
  • Gut mucosal permeability [ Time Frame: 180 days ] [ Designated as safety issue: No ]
    Gut mucosal permeability will be measured by changes from baseline in the gut mucosal integrity as assessed by the lactulose/mannitol test.


Estimated Enrollment: 130
Study Start Date: October 2013
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 of acute alcoholic hepatitis: Anorexia, nausea, 
right upper quadrant pain
  5. Liver biopsy diagnostic of acute AH or at least 2 of the following: Jaundice, leukocytosis, 
hepatomegaly
  6. Elevation of AST > 80 U/L, but < 500 U/L; AST > ALT and ALT < 200 U/L; total bilirubin 
> 3 mg/dL
  7. Ultrasound or CT scan suggesting fatty infiltration of the liver OR liver biopsy showing 
alcoholic hepatitis
  8. Model for End-Stage Liver Disease (MELD) < 20

Exclusion Criteria:

  1. Hypotension with blood pressure < 80/50 after volume repletion
  2. Pregnancy; incarceration; inability to provide consent or lack of appropriate family 
member
  3. Signs of systemic infection: Fever > 39o C; positive blood or ascites cultures within 3 
days of inclusion
  4. Acute gastrointestinal bleeding requiring 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; HIV infection
  6. Previous treatment with corticosteroids or other immunosuppressive medications 
including anti-TNF therapy, calcineurin inhibitors within the previous 3 months
  7. ANA > 1:160; anti-smooth muscle antibody > 1:40; cryoglobulinemia; positive anti-CCP 
or rheumatoid factor
  8. Evidence of acute pancreatitis: CT evidence or amylase or lipase > 4 X upper limit of normal
  9. Serious cardiac, respiratory or neurologic disease or evidence of other liver diseases 
such as autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson disease, hemochromatosis, alpha-1-antitrypsin deficiency
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01922895

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

Locations
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
The Cleveland Clinic
University of Massachusetts, Worcester
University of Louisville
Investigators
Principal Investigator: Mack C Mitchell, M.D. U Texas Southwestern Medical Center
  More Information

No publications provided

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
Study First Received: August 12, 2013
Last Updated: May 16, 2014
Health Authority: United States: Data and Safety Monitoring Board

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

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

ClinicalTrials.gov processed this record on July 22, 2014