Cholestatic Drug-induced Liver Injury

NCT01141322 | Unknown Phase 4 DMC

• 1 other identifier: 96-01-23A
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Cholestatic drug-induced liver injury (DILI) is the severe form of DILI with a grave outcome. Drug-metabolizing enzymes play an important role in the metabolism of drugs. The genetic polymorphism of drug-metabolizing enzymes may influence the activities and expression of these enzymes and thereby affect the susceptibility and severity of DILI. UDP-glucuronosyltransferase (UGT) is an important phase 2 detoxification enzyme, which is related to congenital hyperbilirubinemia. Recently, the genetic polymorphism of UGT1A1 was reported to be associated with jaundice induced by some drugs, and UGT1A7 was shown to be related to the susceptibility of hepatocellular carcinoma and other cancers. Ursodeoxycholic acid (UDCA ) is a hydrophilic bile acid that is increasingly used for the treatment of various cholestatic disorders. The aims of this study are (1) to assess the association of the genetic polymorphism of UGT1A1 and 1A7, and the susceptibility and severity of drug-induced liver injury (DILI), with emphasis on the cholestatic DILI; (2) to evaluate the treatment effect of UDCA in the DILI, with special reference to the cholestatic hepatotoxicity.

Conditions

Hepatitis, Toxic

Keywords

drug-induced liver injury; hepatitis, toxic; ursodeoxycholic acid

Outcome Measures

Primary Outcomes (1)

• severe degree drug-induced liver injury, fatality or liver transplantation

  8 weeks

Study Arms (2)

UDCA treatment

EXPERIMENTAL

Patients with drug-induced liver injury will be randomly allocated to UDCA treatment group: oral intake ursodeoxycholic acid (UDCA) 13-15 mg/kg BW/day into 3 divided doses after meal till the endpoint or the 8th week. UDCA is 100 mg per tab.

Drug: Ursodeoxycholic Acid

Placebo

PLACEBO COMPARATOR

Patients with drug-induced liver injury will be randomly allocated to placebo group. The placebo is of the same color, size and shape as UDCA, and assumed 100 mg per tab. Patients in this group will orally intake 13-15 mg/Kg BW/day of placebo into 3 divided doses after meal as UDCA treatment group, till the endpoint or the 8th week.

Drug: Placebo

Interventions

Ursodeoxycholic Acid DRUG

ursodeoxycholic acid 13-15 mg/kg BW/day into 3 divided doses after meal till endpoint or the 8th week.

Also known as: ursodil, UDCA, urso

UDCA treatment

Placebo DRUG

The placebo is of the same color, size and shape as UDCA, and assumed 100 mg per tab. Patients in this group will orally intake 13-15 mg/Kg BW/day of placebo into 3 divided doses after meal as UDCA treatment group, till the endpoint or the 8th week.

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Drug-induced liver injury, meet the DILIN criteria.

You may not qualify if:

• Other systemic diseases may cause elevation of liver enzymes: viral hepatitis, alcoholic liver disease, autoimmune hepatitis, primary biliary cirrhosis, Wilson's disease, hemochromatosis, congestive heart failure, hypoxia, sepsis.

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead

Study Sites (1)

Taipei Veterans General Hospital

Taipei, Taiwan, 11217, Taiwan

RECRUITING

MeSH Terms

Conditions

Chemical and Drug Induced Liver Injury

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Yi-Shin Huang, M.D.

  Taipei Veterans General Hospital, Taipei, Taiwan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi-Shin Huang, M.D.

CONTACT

+886-2-2871-2121; yshuang@vghtpe.gov.tw

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: June 10, 2010
• Study Start: August 1, 2007
• Primary Completion: April 1, 2010
• Study Completion: July 1, 2010
• Last Updated: June 10, 2010

Record last verified: 2010-06

Locations

TW (1)