Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis (InTeam)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of North Carolina, Chapel Hill
Sponsor:
Collaborators:
University of Wisconsin, Madison
King's College London
Veterans Medical Research Foundation
Universidad Autonoma de Nuevo Leon
Hospital Vall d'Hebron
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02075918
First received: February 27, 2014
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

Purpose: To improve the diagnosis and assessment of severity of acute alcoholic hepatitis Participants: Patients admitted to one of ten centers with acute alcoholic hepatitis Procedures (methods): Consecutive patients admitted with acute alcoholic hepatitis will be enrolled in an NIH U01 study of acute alcoholic hepatitis where liver tissue, blood and stool will be collected to discover and validate factors associated with diagnosis, severity of disease and survival.


Condition
Alcoholic Hepatitis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Diagnosis and Severity of Alcoholic Hepatitis [ Time Frame: 3 months after end of Study ] [ Designated as safety issue: No ]
    Utilizing liver tissue, blood samples, and stool and urine samples, InTeam will aim to discover and validate factors associated with the diagnosis and severity of Alcoholic hepatitis.


Secondary Outcome Measures:
  • Major Liver Complications [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
    As an observational study, we will collect data regarding major liver complications such as, ascites, renal failure, encephalopathy, and bleeding.

  • Death/Transplantation [ Time Frame: 3 months after end of study ] [ Designated as safety issue: No ]
    As an observational study, we will collect the data regarding number the survival of Alcoholic Hepatitis by considering deaths and transplantations.


Biospecimen Retention:   Samples With DNA

Serum, Plasma, Whole Blood DNA, PBMCs, Urine, Stool, Liver Biopsy


Estimated Enrollment: 700
Study Start Date: May 2014
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2018 (Final data collection date for primary outcome measure)
Detailed Description:

The development of new targeted therapies for alcoholic hepatitis (AH) is one of the more urgent needs in clinical hepatology. To reach this goal, large multidisciplinary networks are required. The proposed initiative "Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis" (InTeam) will coordinate a multidisciplinary group composed of clinicians, physician-scientists, basic scientists and bioinformatics experts. The overarching hypothesis of InTeam is that the most rational way to provide a useful framework for future clinical trials in (AH) consists of the (i) determination of key drivers of the disease process, (ii) classification of molecular profiles and subtypes of AH, and (iii) identification of "druggable" targets based on both key drivers and molecular classification. Moreover, mouse models for AH are lacking making it impossible to evaluate promising targets in preclinical mouse studies in a meaningful manner. For this purpose, InTeam will integrate data obtained from molecular pathology studies in human AH and functional studies of key pathways in animal models. The proposed InTeam consortium includes three research projects, ten clinical centers, a Human Biorepository and a Mouse Models Core. The Human Biorepository Core will generate the to-date largest collection of samples from patients with AH from 10 academic liver centers and a comprehensive database that will serve as a basis for the proposed translational studies and be a valuable asset for the broader scientific community. The Mouse Models core will conduct murine studies after establishing and evaluating mouse models of AH based on the pathophysiology and molecular drivers of human AH determined by this consortium.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with an episode of alcoholic hepatitis fulfilling the inclusion criteria will be eligible to participate in the study. Those patients who meet one or more exclusion criteria will not be included. We will prospectively include patients with the following inclusion criteria

Criteria

Inclusion Criteria:

  • Patients ≥18 and <70 years of age.
  • Active alcohol abuse defined according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) and excessive alcohol consumption prior to admission (> 60 g per day for men and> 40 g per day for women).
  • Moderate elevation of aminotransferases (usually less than 300 U / L) with a characteristic pattern of AST/ ALT ratio of 2:1.
  • Elevated serum GGT and bilirubin levels.
  • Absence of prior autoimmune liver disease (ANA<1/80, SMA<1/80, LKM1 neg, AMA neg).
  • Absence of hepatitis B and C and HIV infection (anti-HCV, surface HBV antigen and anti-HIV neg).
  • Patients with decompensated alcoholic cirrhosis will be suitable for inclusion (eg, acute gastrointestinal bleeding, acute renal failure, hepatic encephalopathy and bacterial infections).
  • Because there are no non-diagnostic tools to diagnose alcoholic hepatitis, histological confirmation is required in all patients (preferably through a transjugular biopsy): alcoholic hepatitis will be diagnosed on the presence of the following histologic features:
  • Steatosis (either macro or microvesicular).
  • Hepatocellular damage (eg, hepatocyte ballooning and presence of Mallory-Denk bodies).
  • Inflammatory infiltrate (predominantly polymorphonuclear cells).
  • Pericellular or sinusoidal fibrosis.

Exclusion Criteria:

  • Hepatocellular carcinoma.
  • Complete portal vein thrombosis.
  • Advanced or terminal extrahepatic diseases (eg heart failure, advanced lung diseases, advanced oncologic diseases).
  • Lack of consent to participate in the study.
  • Pregnancy.
  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: NCT02075918

Contacts
Contact: Ramon Bataller, MD (919) 966-4812 ramon_bataller@med.unc.edu

Locations
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Principal Investigator: Ramon Bataller, MD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
University of Wisconsin, Madison
King's College London
Veterans Medical Research Foundation
Universidad Autonoma de Nuevo Leon
Hospital Vall d'Hebron
Investigators
Principal Investigator: Ramon Bataller, MD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02075918     History of Changes
Other Study ID Numbers: 12-2016, 1U01AA021908-01
Study First Received: February 27, 2014
Last Updated: September 8, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Hepatitis, Alcoholic
Hepatitis
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

ClinicalTrials.gov processed this record on October 01, 2014