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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01922895
Recruitment Status : Suspended (Lack of funding)
First Posted : August 14, 2013
Last Update Posted : November 24, 2021
Sponsor:
Collaborators:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
The Cleveland Clinic
University of Massachusetts, Worcester
University of Louisville
Information provided by (Responsible Party):
Mack Mitchell, University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE August 12, 2013
First Posted Date  ICMJE August 14, 2013
Last Update Posted Date November 24, 2021
Actual Study Start Date  ICMJE August 2013
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2013)
MELD score [ Time Frame: 180 days ]
Improvement in MELD score over 180 day study duration.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 12, 2013)
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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
Official Title  ICMJE Novel Therapies in Moderately Severe Acute Alcoholic Hepatitis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Condition  ICMJE Acute Alcoholic Hepatitis
Intervention  ICMJE
  • Dietary Supplement: Lactobacillus Rhamnosus GG
    Probiotic nutritional supplement; Lactobacillus Rhamnosus GG
    Other Name: Culturelle
  • Drug: Placebo for Probiotic
    Capsule manufactured without active ingredients.
    Other Name: Dummy capsule
Study Arms  ICMJE
  • Placebo Comparator: Placebo for Probiotic
    Placebo capsule that matches the probiotic capsule in appearance will be given once daily for 180 days.
    Intervention: Drug: Placebo for Probiotic
  • Active Comparator: Lactobacillus Rhamnosus GG
    Dietary supplement capsule (Lactobacillus Rhamnosus GG) will be given once daily for 180 days.
    Intervention: Dietary Supplement: Lactobacillus Rhamnosus GG
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Actual Enrollment  ICMJE
 (submitted: November 2, 2020)
53
Original Estimated Enrollment  ICMJE
 (submitted: August 12, 2013)
130
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01922895
Other Study ID Numbers  ICMJE STU 092012-012
U01AA021893-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mack Mitchell, University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE
  • National Institute on Alcohol Abuse and Alcoholism (NIAAA)
  • The Cleveland Clinic
  • University of Massachusetts, Worcester
  • University of Louisville
Investigators  ICMJE
Principal Investigator: Mack C Mitchell, M.D. U Texas Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP