Drug-Induced Liver Injury (DILI) Network Retrospective

Drug Induced Liver Injury Clinical Trial

— ILIAD  

Official title:

Idiosyncratic Liver Injury Associated With Drugs (ILIAD): A Retrospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00360646
• Other study ID #: Pro00113362
• Secondary ID: 2U01DK065176-21P
• Status: Recruiting
• Start date: September 2004
• Est. completion date: July 31, 2028

Study information

• Verified date: April 2024
• Source: Duke University
• Contact: Eilene Pham
• Phone: 919-660-7253
• Email: eilene.pham[@]duke.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: July 31, 2028
• Est. primary completion date: July 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chemical and Drug Induced Liver Injury
• Drug Induced Liver Injury
• Wounds and Injuries

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	NIH Clinical Site	Bethesda	Maryland
United States	Univeristy of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Indiana University	Indianapolis	Indiana
United States	University of Southen California	Los Angeles	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Thomas Jefferson	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maintain a registry of cases in the ILIAD database	maintain a registry of cases in the ILIAD database	July 2028

External Links

•   Multi-center, Longitudinal Study of Drug-and-CAM-Induced Liver Injury
•   The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is part of the National Institutes of Health (NIH)