DILIN - Prospective Study

Liver Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00345930
• Other study ID #: Pro00113362_1
• Secondary ID: U01DK065176Pro00
• Status: Recruiting
• Start date: September 2004
• Est. completion date: July 31, 2028

Study information

• Verified date: April 2024
• Source: Duke University
• Contact: Eilene Pham
• Phone: 9196607253
• Email: eilene.pham[@]duke.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4000
• Est. completion date: July 31, 2028
• Est. primary completion date: July 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Liver Diseases

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	NIH Clinical Site	Bethesda	Maryland
United States	Univeristy of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Indiana University	Indianapolis	Indiana
United States	University of Southern California	Los Angeles	California
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Thomas Jefferson	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008 Dec;135(6):1924-34, 1934.e1-4. doi: 10.1053/j.gastro.2008.09.011. Epub 2008 Sep 17. — View Citation

Fontana RJ, Watkins PB, Bonkovsky HL, Chalasani N, Davern T, Serrano J, Rochon J; DILIN Study Group. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Saf. 2009;32(1):55-68. doi: 10.2165/00002018-200932010-00005. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Develop a database of recent DILI cases	develop a database of recent DILI cases	July 2028

External 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.