Summary

Eligibility
for people ages 2 years and up (full criteria)
Healthy Volunteers
healthy people welcome
Location
at Los Angeles, California and other locations
Dates
study started
completion around
Principal Investigator
by Gina Choi, MD
Headshot of Gina Choi
Gina Choi

Description

Summary

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. Recently added acute cases enrollment that meets criteria to the protocol. Also added Fibroscans to the protocol that will be completed at baseline and follow-up on chronic subjects.

Official Title

A Multi-Center, Longitudinal Study of Drug-and CAM-Induced Liver Injury

Details

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 including liver elastography (FibroScans) and biological specimens are collected. Patients who satisfy the definition of chronic DILI will be evaluated with additional FibroScans at 12, 24, 36 and 48 months thereafter.

Keywords

Liver Diseases, 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

Eligibility

You can join if…

Open to people ages 2 years and up

  • 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.

You CAN'T join if...

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.

Locations

  • University of Southern California accepting new patients
    Los Angeles California 90033 United States
  • Indiana University accepting new patients
    Indianapolis Indiana 46202-5111 United States

Lead Scientist at UCLA

  • Gina Choi, MD
    HS Associate Clinical Professor, Medicine. Authored (or co-authored) 89 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Duke University
Links
Multi-center, Longitudinal Study of Drug- and CAM-Induced Liver Injury. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports biomedical research and disseminates research findings & health information to the public. Sign up for this study
ID
NCT00345930
Study Type
Observational
Participants
Expecting 4000 study participants
Last Updated