Ignite Creation Date:
2024-06-16 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06446609
Status:
RECRUITING
Last Update Posted:
2024-06-11
First Post:
2024-05-15
Brief Title:
Drug-induced Liver Injury Itching Study
Sponsor:
University of Nottingham
Organization:
University of Nottingham
Study Overview
Official Title:
Understanding the Natural History and Impact of Itching Pruritus in Patients With Drug-induced Liver Injury DILI
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Idiosyncratic drug-induced liver injury DILI is an unpredictable adverse hepatic reaction to a medication used in its therapeutic dose DILI is the second most common cause of itching in adult Hepatology after biliary obstruction In particular cholestatic or mixed pattern types of DILI in which bile flow from the liver is impaired are associated with long-lasting effects as well as reduced quality of life There is therefore an urgent need to determine the incidence and natural history of itching in DILI and establish a network of centres that will form a basis for a clinical trial to investigate a novel intervention to treat these
Detailed Description:
In Idiosyncratic drug-induced liver injury DILI the adverse effect is unexpected from the known pharmacological action of the agent The incidence of DILI is estimated as between 14-19 per 100000 inhabitants a population-based study in Europe reported the annual incidence as 191 per 100000 Despite its rarity idiosyncratic DILI accounts for 7-15 of the cases of acute liver failure in Europe although many cases resolve quickly DILI is the most frequent reason for the market withdrawal of an approved drug In addition DILI occurs in association with many drugs and shows heterogeneity There are no markers that can effectively pre-empt and prevent DILI or monitor the severity and course of the adverse event It is also emerging that immunotherapy regimens devised for cancer treatment are associated with increased risk of DILI development
Further characterisation and understanding of this is urgently needed to distinguish from other causes and develop more effective treatments Age smoking metabolic syndrome co-morbidity and other yet unidentified factors may generate an environment of oxidative stress that contributes to DILI Therefore in-depth phenotyping is needed to develop a refined understanding of drug-related factors host genetic and environmental risk factors linked to disease characteristics that would enable us to pre-empt and treat DILI Further work is also needed to identify patients who may benefit from new treatments becoming available so identification and analysis of certain sub-groups is of value
Based on the pattern of liver biochemistry at the time of initial presentation DILI is classified as cholestatic hepatocellular or mixed type Pruritus itching occurs in a proportion of patients with cholestatic and mixed pattern of DILI Most DILI manifestations resolve within 3 months following the prompt withdrawal of the causative medication but symptoms persist for 6 months in 188 and for 1 year in 124 persistence of symptoms are more common in cholestatic pattern of DILI Those with persistent DILI have significantly lower SF-36 quality of life scores at baseline and during follow-up
Research is needed to identify patients who may benefit from new treatments becoming available so identification and analysis of certain sub-groups is of value DILI is the second most common cause of itching in adult Hepatology after biliary obstruction Cholestatic or mixed pattern of DILI is associated with chronicity as well as reduced quality of life
There is currently limited data available on the incidence and impact of pruritus in DILI Although therapeutics targeting bile acid pathways have been deployed to tackle cholestatic pruritus in primary biliary cholangitis PBC their application in cholestatic DILI requires investigation Further there is now also effective treatment that have been licensed to improve quality of life of patients with itching as well as potentially improving natural history of cholestatic conditions
Further characterisation and understanding of this is urgently needed to distinguish from other causes and develop more effective treatments Age smoking metabolic syndrome co-morbidity and other yet unidentified factors may generate an environment of oxidative stress that contributes to DILI Therefore in-depth phenotyping is needed to develop a refined understanding of drug-related factors host genetic and environmental risk factors linked to disease characteristics that would enable us to pre-empt and treat DILI Further work is also needed to identify patients who may benefit from new treatments becoming available so identification and analysis of certain sub-groups is of value
Based on the pattern of liver biochemistry at the time of initial presentation DILI is classified as cholestatic hepatocellular or mixed type Pruritus itching occurs in a proportion of patients with cholestatic and mixed pattern of DILI Most DILI manifestations resolve within 3 months following the prompt withdrawal of the causative medication but symptoms persist for 6 months in 188 and for 1 year in 124 persistence of symptoms are more common in cholestatic pattern of DILI Those with persistent DILI have significantly lower SF-36 quality of life scores at baseline and during follow-up
Research is needed to identify patients who may benefit from new treatments becoming available so identification and analysis of certain sub-groups is of value DILI is the second most common cause of itching in adult Hepatology after biliary obstruction Cholestatic or mixed pattern of DILI is associated with chronicity as well as reduced quality of life
There is currently limited data available on the incidence and impact of pruritus in DILI Although therapeutics targeting bile acid pathways have been deployed to tackle cholestatic pruritus in primary biliary cholangitis PBC their application in cholestatic DILI requires investigation Further there is now also effective treatment that have been licensed to improve quality of life of patients with itching as well as potentially improving natural history of cholestatic conditions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None