DILIN's Prospective Study

This study is currently recruiting participants.
Verified February 2014 by Duke University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00345930
First received: June 27, 2006
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to identify individuals who have suffered a liver injury arising as an idiosyncratic reaction to a prescription drug or a complementary and alternative medicine.


Condition
Liver Diseases

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: A Multi-Center, Longitudinal Study of Drug-and CAM-Induced Liver Injury

Resource links provided by NLM:


Further study details as provided by Duke University:

Biospecimen Retention:   Samples With DNA

Samples with DNA


Estimated Enrollment: 900
Study Start Date: September 2004
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
2
Individuals without drug induced liver disease
1
Individuals with drug induced liver disease

Detailed Description:

Liver injury due to prescription and non-prescription medication use is a medical, scientific and public health problem of increasing frequency and importance in the United States. Indeed, drug-induced liver injury (DILI) is the most important reason for non-approval, withdrawal, limitation in use and clinical monitoring by the Food and Drug Administration (FDA). However, detection of signals for liver injury frequently relies upon the reporting of cases by practitioners to health authorities in post-marketing surveillance. Under-reporting of cases, lack of mandatory reporting systems, and difficulties in establishing a diagnosis make the current system sub-optimal. Moreover, with the growing use of complementary and alternative medications (CAM), there have also been increasing reports of liver toxicity due to various non-prescription herbal, dietary and food additive supplements. Because the manufacturing, dispensing and testing of these products is not regulated, the hepatotoxic potential of these formulations is poorly characterized or completely unknown.

The DILIN Prospective Study is a multi-centered epidemiological study designed to gather clinical information and biological specimens on cases of suspected liver injury due to drugs and CAM. The goals of this study are to develop a database of recent DILI cases, identify the clinical, environmental and genetic risk factors that predict DILI, develop standardized instruments and terminology and perform careful longitudinal follow-up of DILI subjects. Biological samples collected will be used in future studies of the mechanisms and genetics of DILI.

Patients who are referred to one of the DILIN clinical sites and who, in the opinion of gastroenterologist/hepatologist, experienced a drug-induced liver injury are enrolled. Detailed clinical data and biological specimens are collected. Clinical data will be reviewed by the DILIN Causality Committee and the final determination on whether the subject qualifies as a bona fide DILI case is made by consensus opinion. DILI cases (only) are followed for at least 6 months to derive the longitudinal profile of drug-and CAM-induced liver injury. Detailed clinical data and biological specimens are collected. Patients who satisfy the definition of chronic DILI will be evaluated at 12 months and 24 months thereafter.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Patients who have suffered a drug induced liver injury and meet inclusion and exclusion criteria

Criteria

Inclusion Criteria:

  • Age > 2 years at enrollment into the study.
  • Evidence of liver injury that is known or suspected to be related to consumption of a drug or CAM product in the 6-month period prior to enrollment.
  • Written Informed consent from the patient or the patient's legal guardian.
  • Documented clinically important DILI, defined as any of the following:

    1. ALT or AST >5 x ULN or A P'ase >2 x ULN confirmed on at least 2 consecutive blood draws in patients with previously normal values.
    2. If baseline (BL) ALT, AST or A P'ase are known to be elevated, then ALT or AST >5 x BL or A P'ase >2 x BL on at least 2 consecutive blood draws. "Baseline" is defined as the average of at least 2 measurements performed during the 12-month period prior to starting the DILI medication.
    3. Any elevation of ALT, A P'ase, or AST, associated with (a) increased total bilirubin [ ≥ 2.5 mg/dL], in absence of prior diagnosis of liver disease, Gilbert's syndrome, or evidence of hemolysis or (b) coagulopathy with INR > 1.5 in absence of coumadin therapy or known vitamin K deficiency.

Exclusion Criteria:

Patients with any of the following will not be eligible for participation:

  • Competing cause of acute liver injury such as hepatic ischemia that is felt by the investigator to be the primary reason for observed liver injury and supported by laboratory tests, serologies, liver biopsy, or radiology.
  • Known, pre-existing autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or other chronic biliary tract disease which may confound the ability to make a diagnosis of DILI.
  • Acetaminophen hepatotoxicity.
  • Liver/bone marrow transplant prior to the development of drug- or CAM-induced liver injury.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00345930

Contacts
Contact: Katherine Galan, RN 919-668-8579 katherine.galan@duke.edu
Contact: Nidia Rosadoi 305-974-0424 nidia.rosado@duke.edu

Locations
United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Susan Milstein, RN, BSN    323-224-5441    smilstei@usc.edu   
Contact: None Available         
Principal Investigator: Andrew Stolz, MD         
California Pacific Medical Center Active, not recruiting
San Fransisco, California, United States, 94120
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202-5111
Contact: Angie Plummer    317-278-9296    plummera@iupui.edu   
Contact: Audrey Corne, RN, CCRN    317-287-3062    acorne@iupui.edu   
Principal Investigator: Naga P Chalasani, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109-0362
Contact: Suzanne Welch    734-936-4886    swelc@umich.edu   
Contact: Jordan Kridler    734-936-4886      
Principal Investigator: Robert J Fontana, MD         
United States, Minnesota
Mayo Clinic College of Medicane Active, not recruiting
Rochester, Minnesota, United States, 55905
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   
Contact: None Available         
Principal Investigator: Paul B Watkins, MD         
United States, Pennsylvania
Albert Einstein Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Maricruz Velez, MPH    215-955-2970    VegaMari@einstein.edu   
Contact: None Available         
Principal Investigator: Victor J Navarro, MD         
United States, Texas
UT Soutwestern Medical Center at Dallas Active, not recruiting
Dallas, Texas, United States, 75390
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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00345930     History of Changes
Other Study ID Numbers: Pro00017208_1, 5 U01-DK065176-11
Study First Received: June 27, 2006
Last Updated: February 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Complementary and alternative medicine
Complementary therapies
Alternative therapies
Prescription Drugs
Non prescription Drugs
Liver Disease
Chemical Ind
Phenotype
Proteomics
Metabolomics
Cholestatic Liver Injury
Hepatocellular Liver Injury
Mixed Liver Injury
Matched Case Control Studies
Genotype
Liver Dis
Chem Ind

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 23, 2014