Clinical trial NCT00360646: Drug-Induced Liver Injury (DILI) Network Retrospective
Official title: Idiosyncratic Liver Injury Associated With Drugs (ILIAD): A Retrospective Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Drug Induced Liver Injury
Keywords: LIVER DIS
CHEM IND
Drugs
Drug induced liver injury
phenotype
cholestatic liver injury
hepatocellular liver injury
mixed liver injury
genotype
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2006-08-04
Enrollment: 400
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: maintain a registry of cases in the ILIAD database
timeFrame: July 2028
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southen California
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Bethesda
country: United States
facility: NIH Clinical Site
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Chapel Hill
country: United States
facility: Univeristy of North Carolina at Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson
state: Pennsylvania
Study officials:
affiliation: Duke University
name: Huiman X. Barnhart, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: Robert Fontana, MD
role: STUDY_CHAIR
References:
citation: 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.