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Drug-Induced Liver Injury (DILN)Network Retrospective (ILIAD)

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ClinicalTrials.gov Identifier: NCT00360646
Recruitment Status : Recruiting
First Posted : August 4, 2006
Last Update Posted : July 26, 2017
Information provided by (Responsible Party):

Study Description
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 caused by four specific drugs, 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.

Condition or disease
Drug Induced Liver Injury

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.

Study Design

Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Idiosyncratic Liver Injury Associated With Drugs (ILIAD): A Retrospective Study
Study Start Date : September 2004
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018
Groups and Cohorts

Subjects with liver injury
Subjects without liver injury

Outcome Measures

Biospecimen Retention:   Samples With DNA
Samples with DNA

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with liver injury ascribed to any drug or HDS/CAM agent which the DILI onset date occurred beyond six months from enrollment.

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00360646

Contact: Kathy M Galan, RN 919-668-8579 Galan006@mc.duke.edu
Contact: Theresa O'Riellly 919-668-8465 theresa.o'rielly@duke.edu

United States, California
University of Southen California Recruiting
Los Angeles, California, United States, 90033
Contact: Susan Milstein, RN    323-442-2699    smilstei@usc.edu   
Contact: Neil Kaplowitz, MD    323-442-5576    kaplowit@usc.edu   
Principal Investigator: Andrew Stolz, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202-5111
Contact: Audrey Corne, RN, CCRN    317-278-3062    acorne@iupui.edu   
Principal Investigator: Naga P Chalasani, MD         
United States, Maryland
NIH Clinical Site Recruiting
Bethesda, Maryland, United States, 20892
Contact: Beverly Niles    301-451-0659    beverly.niles@nih.gov   
Contact: Chris Koh, MD       christopher.koh@nih.gov   
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109-0362
Contact: Kendall Dabois    734-644-2277    kendalld@umich.edu   
Principal Investigator: Robert J Fontana, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Stephanie Pagan    212-241-8035    stephanie.pagan@mssm.edu   
Contact: Jospeh Odin, MD    212-241-8035    joseph.odin@mountsinai.org   
United States, North Carolina
Univeristy of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599-7600
Contact: Tracy Russell    919-843-2376    trussell@med.unc.edu   
Principal Investigator: Paul B Watkins, MD         
United States, Pennsylvania
Albert Einstein Recruiting
Philadelphia, Pennsylvania, United States, 19141
Contact: Manisha Verma, MD MPH    215-456-1026    Vermam@einstein.edu   
Principal Investigator: Victor J. Navarro, MD         
Sponsors and Collaborators
Duke University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Huiman X. Barnhart, PhD Duke University
Study Chair: Paul Watkins, MD University of North Carolina, Chapel Hill
More Information

Additional Information:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00360646     History of Changes
Other Study ID Numbers: Pro00017208
First Posted: August 4, 2006    Key Record Dates
Last Update Posted: July 26, 2017
Last Verified: April 2017

Keywords provided by Duke University:
Drug induced liver injury
cholestatic liver injury
hepatocellular liver injury
mixed liver injury

Additional relevant MeSH terms:
Wounds and Injuries
Chemical and Drug Induced Liver Injury
Liver Diseases
Digestive System Diseases
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Liver Extracts