Hepatitis, ToxicPhase 4DILINCT01141322
Cholestatic Drug-induced Liver Injury
A Phase 4 study testing Ursodeoxycholic Acid in people with Hepatitis, Toxic, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hepatitis, Toxic
- What is being tested?
- Ursodeoxycholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2007to Jul 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Drug-induced liver injury, meet the DILIN criteria.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Veterans General Hospital
Taipei, Taiwan, 11217
Yi-Shin Huang, M.D., +886-2-2871-2121 ext. 2015, yshuang@vghtpe.gov.tw
Yi-Shin Huang, M.D.
About this study
Official title: Cholestatic Drug-induced Liver Injury: Correlation With Genotypes of UGT1A1 and 1A7, and Treatment Effect of Ursodeoxycholic Acid
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.
Read the detailed description
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.
Owing to the limited number of DILI patients, 3 years are needed in this study. Each year, a total of 60 patients with DILI and 60 age- and sex-matched controls will be enrolled in this study. Their genetic polymorphisms of UGT1A1 and UGT1A7 will be assessed using the real time PCR, or PCR with RFLP. The DILI patients will be randomized to UDCA Treatment group and Control group. UDCA 13-15 mg/kg/day with 3 divided doses will be administered to the patients with Treatment group.
The frequencies of genotypes of UGT1A1 and 1A7 will be compared between DILI cases and controls, survival cases and non-survival cases, and cholestatic and non-cholestatic cases. Chi-square test, with or without Yates' correction, will be used to compare the categorical parameters. A paired t test will be performed to compare the continuous parameters. Odds ratios (OR) and confidence intervals (CI) will be calculated using a logistic regression analysis. The multivariate logistic regression analysis will be applied to check on the OR, adjusted with other possible risk factors. Survival rates will be estimated from survival curves based on the Kaplan-Meier method and compared with the log-rank test between the UDCA Treatment group and Control group.
We believe that this pharmacogenetic study may help us realize the pathogenesis of cholestatic DILI, and the clinical trial can elucidate the therapeutic value of UDCA in the DILI, especially in the cholestatic hepatotoxicity.
- Conditions
- Hepatitis, Toxic
- Being tested
- Ursodeoxycholic Acid, Placebo
- Keywords
- drug-induced liver injury, hepatitis, toxic, ursodeoxycholic acid
- Medical subject headings
- Chemical and Drug Induced Liver Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ursodeoxycholic AcidDrug
Also called ursodil, UDCA, urso
ursodeoxycholic acid 13-15 mg/kg BW/day into 3 divided doses after meal till endpoint or the 8th week.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
severe degree drug-induced liver injury, fatality or liver transplantation
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2010 (estimated)
- Study startAug 2007
- Primary completionApr 2010 (estimated)
- Study completionJul 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis, ToxicStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Investigators
- Yi-Shin Huang, M.D., Principal investigator, Taipei Veterans General Hospital, Taipei, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01141322
- Sponsor's protocol ID
- 96-01-23A
- Acronym
- DILI
- Status last verified
- Jun 2010
- First submitted
- 12 Jan 2010
- Last updated
- 10 Jun 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cholestatic Drug-induced Liver Injury: Correlation With Genotypes of UGT1A1 and 1A7, and Treatment Effect of Ursodeoxycholic Acid
- ClinicalTrials.gov ID
- NCT01141322
- Acronym / sponsor ID
- DILI / 96-01-23A
- Conditions
- Hepatitis, Toxic
- Keywords
- drug-induced liver injury, hepatitis, toxic, ursodeoxycholic acid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Study start
- Aug 2007
- Primary completion
- Apr 2010 (estimated)
- Study completion
- Jul 2010 (estimated)
- First posted
- 10 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Owing to the limited number of DILI patients, 3 years are needed in this study. Each year, a total of 60 patients with DILI and 60 age- and sex-matched controls will be enrolled in this study. Their genetic polymorphisms of UGT1A1 and UGT1A7 will be assessed using the real time PCR, or PCR with RFLP. The DILI patients will be randomized to UDCA Treatment group and Control group. UDCA 13-15 mg/kg/day with 3 divided doses will be administered to the patients with Treatment group.
The frequencies of genotypes of UGT1A1 and 1A7 will be compared between DILI cases and controls, survival cases and non-survival cases, and cholestatic and non-cholestatic cases. Chi-square test, with or without Yates' correction, will be used to compare the categorical parameters. A paired t test will be performed to compare the continuous parameters. Odds ratios (OR) and confidence intervals (CI) will be calculated using a logistic regression analysis. The multivariate logistic regression analysis will be applied to check on the OR, adjusted with other possible risk factors. Survival rates will be estimated from survival curves based on the Kaplan-Meier method and compared with the log-rank test between the UDCA Treatment group and Control group.
We believe that this pharmacogenetic study may help us realize the pathogenesis of cholestatic DILI, and the clinical trial can elucidate the therapeutic value of UDCA in the DILI, especially in the cholestatic hepatotoxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| UDCA treatment | Experimental | Drug: Ursodeoxycholic AcidPatients 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. |
| Placebo | Placebo comparator | Drug: PlaceboPatients 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Drug-induced liver injury, meet the DILIN criteria.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ursodeoxycholic AcidAlso: ursodil, UDCA, ursoursodeoxycholic acid 13-15 mg/kg BW/day into 3 divided doses after meal till endpoint or the 8th week. | Drug | UDCA treatment |
| PlaceboThe 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 |
Primary outcome
severe degree drug-induced liver injury, fatality or liver transplantation
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yi-Shin Huang, M.D. principal investigator
Taipei Veterans General Hospital, Taipei, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ursodeoxycholic Acid in people with Hepatitis, Toxic, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yi-Shin Huang, M.D. (+886-2-2871-2121 ext. 2015, yshuang@vghtpe.gov.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
severe degree drug-induced liver injury, fatality or liver transplantation (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2010.