Drug-Induced Liver Injury (DILI) Network Retrospective

NCT ID: NCT00360646

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2028-07-31

Brief Summary

The purpose of this study is to establish retrospectively a nationwide registry of patients who have suffered drug-induced liver injury (DILI), and to collect, immortalize, and store serum, DNA, and lymphocytes from these patients. ILIAD will serve as a resource for subsequent mechanistic investigations into the basis of severe idiosyncratic DILI. The primary goal of the ILIAD protocol is to create: (a) a clinical database consisting of individuals who have experienced severe DILI and the relevant clinical data concerning the episode of DILI; and, (b) to create a bank of biological specimens obtained from these individuals. These biological specimens will be DNA, plasma, and immortalized lymphocytes. Immortalized lymphocytes will provide unlimited amounts of genomic DNA for study as well as living immune cells for phenotyping studies.

A secondary goal of the ILIAD protocol is to maintain a registry of cases in the ILIAD database so that they may be recontacted in the future. It is expected that this will facilitate additional studies exploring the mechanisms of DILI.

Detailed Description

Drug-induced liver injury (DILI) is the single most common reason for regulatory actions concerning drugs, including failure to gain approval for marketing, removal from the market place, and restriction of prescribing indications. DILI is also a significant cause of morbidity and mortality in many patient populations. To stimulate and facilitate research into DILI, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has recently established the Drug-Induced Liver Injury Network (DILIN). One of the initial projects to be conducted by the network is to retrospectively establish a nationwide registry of patients who have suffered severe idiosyncratic liver injury associated with any drugs (ILIAD) and HDS agents, and to collect, immortalize and store serum, DNA, and lymphocytes from these patients (hereafter referred to as the "ILIAD protocol"). This ILIAD protocol will serve as a resource for subsequent mechanistic investigations of the basis for susceptibility to severe idiosyncratic DILI.

The network will initially identify people who have developed DILI onset beyond 6 months of enrollment due to all drugs or HDS/CAM cases that did not meet the entrance criteria for the Prospective study.

The specific aims are as follows:

1. Establish and maintain a clinical database of these people that contains relevant clinical data.

2. Establish a bank of biological specimens (serum, DNA, and immortalized lymphocytes) prepared from cases and control in the clinical database.

3. Maintain a registry including yearly updated contact information of the subjects enrolled in the clinical database so that it is possible to recontact these individuals at a later date to offer participation in studies which are not part of the current proposal.

Conditions

Drug Induced Liver Injury

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

Subjects with liver injury

No interventions assigned to this group

Subjects without liver injury

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Screening Criteria

To be included in the ILIAD registry, the following criteria must be satisfied:

• The treating gastroenterologist / hepatologist or health care professional must believe that the subject suffered drug-induced liver injury;
• The subject must be alive and the date of onset of the qualifying DILI episode must have occurred on or after January 1, 1994;
• Evidence of injury that is known or suspected to be related to consumption of a drug or HDS/CAM product
• The subject is taking only one of these drugs or HDS agent(s) in the period leading up to the onset of the qualifying DILI episode;
• Have clinically important DILI defined in terms of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (Alk Phos).
• Sufficient documentation of the event for the Causality Committee to make a determination.

Exclusion Criteria

Subjects will be excluded according to the following criteria:

• are not willing to have medical information and blood samples taken;
• are unable to adequately give informed consent to participate in the study including the blood draw for the genetic component;
• age < 2 years old at the time of study enrollment (due to blood volume requirements).
• Have a competing cause of liver injury such as hepatic ischemia that the investigator felt to be the primary reason for the observed liver injury. Known, pre-existing autoimmune hepatitis; primary biliary cirrhosis, primary sclerosing cholangitis, or other chronic biliary tract disease. Subjects are excluded due to acetaminophen hepatoxicity or liver transplant or allogeneic bone marrow transplant prior to development of drug-CAM induced liver injury.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huiman X. Barnhart, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Robert Fontana, MD

Role: STUDY_CHAIR

University of Michigan

Locations

University of Southen California

Los Angeles, California, United States

Site Status: RECRUITING

Indiana University

Indianapolis, Indiana, United States

Site Status: RECRUITING

NIH Clinical Site

Bethesda, Maryland, United States

Site Status: RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Univeristy of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status: RECRUITING

Thomas Jefferson

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Eilene Pham

Role: CONTACT

eilene.pham@duke.edu

919-660-7253

Matt Baum

Role: CONTACT

matt.baum@duke.edu

919-668-0486

Facility Contacts

Susan Milstein, RN

Role: primary

smilstei@usc.edu

323-442-2699

Neil Kaplowitz, MD

Role: backup

kaplowit@usc.edu

323-442-5576

Jennifer Terrell

Role: primary

jkramey@iu.edu

317-278-6266

Jaha Norman-Wheeler

Role: primary

jaha.norman-wheeler@nih.gov

301-435-6122

Chris Koh, MD

Role: backup

christopher.koh@nih.gov

Josefa Kaganove

Role: primary

kaganovj@med.umich.edu

Jacquee Simpson

Role: primary

Jacqueline_Simpson@med.unc.edu

Katrin Koy

Role: primary

koykatri@einstein.edu

215-456-2004

References

Rochon J, Protiva P, Seeff LB, Fontana RJ, Liangpunsakul S, Watkins PB, Davern T, McHutchison JG; Drug-Induced Liver Injury Network (DILIN). Reliability of the Roussel Uclaf Causality Assessment Method for assessing causality in drug-induced liver injury. Hepatology. 2008 Oct;48(4):1175-83. doi: 10.1002/hep.22442.

Reference Type: BACKGROUND

PMID: 18798340 (View on PubMed)

Related Links

https://dilin.org/

Multi-center, Longitudinal Study of Drug-and-CAM-Induced Liver Injury

http://www.niddk.nih.gov

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is part of the National Institutes of Health (NIH)

Other Identifiers

2U01DK065176-21

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00072297

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00017208

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00113362

Identifier Type: -

Identifier Source: org_study_id