Clinical trial NCT02075918: Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis
Official title: Integrated Approaches for Identifying Molecular Targets in Alcoholic Hepatitis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alcoholic Hepatitis
Control Patients
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: University of Wisconsin, Madison
name: King's College London
name: Veterans Medical Research Foundation
name: Hospital Vall d'Hebron
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Yale University
name: Columbia University
name: Weill Medical College of Cornell University
name: University of Alberta
name: TecSalud Investigación Clínica
First posted: 2014-03-03
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Control patients

Brief summary: 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.

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 criteria: Inclusion Criteria:

* Patients 18 ≥ and ≤ 70 years of age.
* Active alcohol abuse within the past 3 months.
* Has an Aspartate Aminotransferase (AST) \> Alanine Aminotransferase (ALT).
* Elevated Total Bilirubin level \> 3.0.
* Absence of autoimmune liver disease (ANA\>1/320).
* Absence of hepatitis B infection.
* A liver biopsy, and/or a clinical picture consistent with alcoholic hepatitis.
* The "Start Date" (is the date of the liver biopsy or ≤ to 1 week \[72 hours is preferred\] from the time of admission).

Exclusion Criteria:

* Hepatocellular carcinoma.
* Complete portal vein thrombosis.
* Advanced or terminal extrahepatic diseases.
* Lack of consent to participate in the study.
* Pregnancy.
* Received more than 3 days of treatment with (prednisolone or pentoxifyllin) prior to start date.

Control patients

Primary outcomes:
measure: Diagnosis and Severity of Alcoholic Hepatitis
timeFrame: 3 months after end of Study
Secondary outcomes:
measure: Major Liver Complications
timeFrame: 3 months after end of study
measure: Death/Transplantation
timeFrame: 3 months after end of study
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ramon Bataller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lang S, Duan Y, Liu J, Torralba MG, Kuelbs C, Ventura-Cots M, Abraldes JG, Bosques-Padilla F, Verna EC, Brown RS Jr, Vargas V, Altamirano J, Caballeria J, Shawcross D, Lucey MR, Louvet A, Mathurin P, Garcia-Tsao G, Ho SB, Tu XM, Bataller R, Starkel P, Fouts DE, Schnabl B. Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis. Hepatology. 2020 Feb;71(2):522-538. doi: 10.1002/hep.30832. Epub 2019 Aug 20.