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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Duke University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00360646
First received: August 2, 2006
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

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
Drug Induced Liver Injury

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Idiosyncratic Liver Injury Associated With Drugs (ILIAD): A Retrospective Study

Further study details as provided by Duke University:

Biospecimen Retention:   Samples With DNA

Samples with DNA


Estimated Enrollment: 200
Study Start Date: September 2004
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Subjects with liver injury
Subjects without 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 drugs (ILIAD), 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 jaundice as a result of treatment with valproic acid, isoniazid, phenytoin, combination clavulanic acid / amoxicillin, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics. In the case of valproic acid, eligibility requires a clinical presentation that is severe enough to prompt hospitalization or is associated with significant biochemical liver dysfunction.

The specific aims are as follows:

  1. Establish and maintain a clinical database of these people that contains relevant clinical data. The target enrollment will be 50-100 individuals with DILI due to each drug.
  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

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with liver injury ascribed to isoniazid, phenytoin, clavulanic acid/amoxicillin, valproic acid, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics

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;
  • The implicated medication is one of the following: isoniazid, phenytoin, combination clavulanic acid / amoxicillin,valproic acid, nitrofurantoin, trimethoprim-sulfamethoxazole, minocycline, and quinolone antibiotics;
  • The subject is taking only one of these medications in the period leading up to the onset of the qualifying DILI episode;
  • For INH, phenytoin, clavulanic acid / amoxicillin, trimethoprim-sulfamethoxazole, or quinolone antibiotics, total serum bilirubin > 2.5 mg/dL;
  • For nitrofurantoin or minocycline, total serum bilirubin > 2.5 mg/dL or documented fibrosis/cirrhosis on liver biopsy;
  • For valproic acid, compatible symptomatic clinical presentation that is severe enough to prompt hospitalization, or that is associated with significant biochemical liver dysfunction, defined as any of the following:

    1. INR > 1.5
    2. Serum AST or ALT > 3 x the baseline level, if the baseline level is elevated.
    3. Bilirubin >1 x ULN or > 1 x the baseline level, if the baseline level is elevated
    4. Unexplained elevated arterial or venous NH3 levels
    5. Liver biopsy showing steatosis
  • 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).
  • are diagnosed with a specific seizure syndrome associated with known genetic defects if the implicated drug is valproate or phenytoin.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00360646

Contacts
Contact: Kathy M Galan, RN 919-668-8579 Galan006@mc.duke.edu
Contact: Nidia Rosado 305-974-0424 nidia.rosado@duke.edu

Locations
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, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109-0362
Contact: Kristin Chesney    734-644-2277    kches@med.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: Joseph Odin, MD    212-241-8035    joseph.odin@mountsinai.org   
Contact: Jawad Ahmad, MD    212-241-8035    jawad.ahmad@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
Investigators
Principal Investigator: Huiman X. Barnhart, PhD Duke University
Study Chair: Paul Watkins, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00360646     History of Changes
Other Study ID Numbers: Pro00017208, 2U01-DK065176-11Revised+, Pro00011992
Study First Received: August 2, 2006
Last Updated: August 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
LIVER DIS
CHEM IND
Drugs
Drug induced liver injury
phenotype
cholestatic liver injury
hepatocellular liver injury
mixed liver injury
genotype

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

ClinicalTrials.gov processed this record on October 23, 2014