Drug Induced Liver InjuryNCT06446609
Drug-induced Liver Injury: Itching Study
An observational study of Drug Induced Liver Injury and Pruritus, run by University of Nottingham at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Induced Liver Injury, Pruritus
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 30 Jun 2025to May 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients recruited are those who meet the criteria for DILI, as defined by Aithal et al. (2011) and endorsed by the EASL DILI Guidelines.
Who may be able to join
- Age ≥18 (no upper age limit) and able to give informed written consent
- Exposure to potential causal agent and diagnosed with suspected acute DILI defined as meeting one of the following analytical thresholds at enrolment (visit 1):
- alanine transaminase (ALT) ≥5 times upper limit of normal (ULN) or
- alkaline phosphatase ≥2 times ULN or
- ALT ≥3 times ULN plus total bilirubin >2 times ULN
- Results from clinical test samples collected within 36h of visit will be acceptable (as DILI is an acute event, patients are expected to recover or deteriorate quickly so enrolment aligned with diagnostic tests is necessary).
Who cannot join
- Patients with comorbidities of eczema and urticaria associated with pruritus
- Patients with existing diagnosis of blood-borne viral hepatitis infection (Hepatitis B/C/E)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Nottingham University Hospitals NHS Trust
Nottingham
Sophie Cusick
About this study
Official title: Understanding the Natural History and Impact of Itching (Pruritus) in Patients With Drug-induced Liver Injury (DILI)
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.
Read the 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 100,000 inhabitants; a population-based study in Europe reported the annual incidence as 19.1 per 100,000. 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 18.8% and for 1 year in 12.4%; 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.
- Conditions
- Drug Induced Liver Injury, Pruritus
- Medical subject headings
- Chemical and Drug Induced Liver Injury, Pruritus
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of pruritus (itching) in patients with DILI
To determine the number of participants who have diagnosis of DILI who report pruritus (itching) compared to the number with other acute non-DILI conditions (e.g. autoimmune hepatitis/viral hepatitis) who report itching within a cohort of patients presenting with acute liver injury.
Measured: 2 years
Secondary outcomes (4)
Duration of itching (pruritus) in patients who present with acute liver injury
To determine the duration and re-occurrence of pruritus (itching) symptoms in patients who are diagnosed with DILI and in those with other acute non-DILI conditions. This will entail a repeated questionnaire at study visits and assessment of medical records to report a timescale of symptoms (weeks).
Measured: 4 years
Severity of itching (pruritus) in patients who present with acute liver injury
To determine the severity of pruritus (itching) symptoms in patients who are diagnosed with DILI and in those with other acute non-DILI conditions. This will entail a repeated questionnaire at study visits to establish the level of itching.
Measured: 4 years
Genetic variants associated with itching (pruritus) in patients who present with acute liver injury
To determine whether any genetic variants of a 77 gene liver cholestasis panel (including causal variants of progressive familial intrahepatic cholestasis (PFIC)) are associated with pruritus in acute liver injury patients. The study will report presence or absence of genetic markers
Measured: 2.5 years
Health status reported by patients who present with acute liver injury
To determine the health status reported by patients who are diagnosed with DILI and in those with other acute non-DILI conditions. This will entail a repeated Short Form 36 Health Survey Questionnaire (SF-36) questionnaire at study visits giving a score ranging from 0 to 100. Higher scores indicate better health status.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study start30 Jun 2025
- Primary completionMay 2027 (estimated)
- Study completionMay 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Drug Induced Liver InjuryStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- Ipsen, National Institute for Health Research, United Kingdom, Nottingham University Hospitals NHS Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06446609
- Sponsor's protocol ID
- 23056
- Status last verified
- Jul 2026
- First submitted
- 15 May 2024
- Last updated
- 27 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, Wilke RA, Avigan M, Kaplowitz N, Bjornsson E, Daly AK. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011 Jun;89(6):806-15. doi: 10.1038/clpt.2011.58. Epub 2011 May 4.
PubMed 21544079Andrade RJ, Chalasani N, Bjornsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, Devarbhavi H, Merz M, Lucena MI, Kaplowitz N, Aithal GP. Drug-induced liver injury. Nat Rev Dis Primers. 2019 Aug 22;5(1):58. doi: 10.1038/s41572-019-0105-0.
PubMed 31439850Bjornsson ES, Bergmann OM, Bjornsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013 Jun;144(7):1419-25, 1425.e1-3; quiz e19-20. doi: 10.1053/j.gastro.2013.02.006. Epub 2013 Feb 16.
PubMed 23419359Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, Weber S, Stirnimann G, Kullak-Ublick G, Cortez-Pinto H, Grove JI, Lucena MI, Andrade RJ, Aithal GP. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023 Jan;43(1):115-126. doi: 10.1111/liv.15378. Epub 2022 Aug 15.
PubMed 35899490Chen HL, Li HY, Wu JF, Wu SH, Chen HL, Yang YH, Hsu YH, Liou BY, Chang MH, Ni YH. Panel-Based Next-Generation Sequencing for the Diagnosis of Cholestatic Genetic Liver Diseases: Clinical Utility and Challenges. J Pediatr. 2019 Feb;205:153-159.e6. doi: 10.1016/j.jpeds.2018.09.028. Epub 2018 Oct 23.
PubMed 30366773European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019 Jun;70(6):1222-1261. doi: 10.1016/j.jhep.2019.02.014. Epub 2019 Mar 27.
PubMed 30926241Fontana RJ, Hayashi PH, Barnhart H, Kleiner DE, Reddy KR, Chalasani N, Lee WM, Stolz A, Phillips T, Serrano J, Watkins PB; DILIN Investigators. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol. 2015 Oct;110(10):1450-9. doi: 10.1038/ajg.2015.283. Epub 2015 Sep 8.
PubMed 26346867
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the Natural History and Impact of Itching (Pruritus) in Patients With Drug-induced Liver Injury (DILI)
- ClinicalTrials.gov ID
- NCT06446609
- Acronym / sponsor ID
- 23056
- Conditions
- Drug Induced Liver Injury, Pruritus
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- Ipsen, National Institute for Health Research, United Kingdom, Nottingham University Hospitals NHS Trust
- Study start
- 30 Jun 2025 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2028 (estimated)
- First posted
- 6 Jun 2024 (actual)
- 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.
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 100,000 inhabitants; a population-based study in Europe reported the annual incidence as 19.1 per 100,000. 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 18.8% and for 1 year in 12.4%; 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients recruited are those who meet the criteria for DILI, as defined by Aithal et al. (2011) and endorsed by the EASL DILI Guidelines.
Key inclusion criteria (6 listed)
- Age ≥18 (no upper age limit) and able to give informed written consent
- Exposure to potential causal agent and diagnosed with suspected acute DILI defined as meeting one of the following analytical thresholds at enrolment (visit 1):
- Results from clinical test samples collected within 36h of visit will be acceptable (as DILI is an acute event, patients are expected to recover or deteriorate quickly so enrolment aligned with diagnostic tests is necessary).
Key exclusion criteria (2 listed)
- Patients with comorbidities of eczema and urticaria associated with pruritus
- Patients with existing diagnosis of blood-borne viral hepatitis infection (Hepatitis B/C/E)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Incidence of pruritus (itching) in patients with DILI
Time frame: 2 years
To determine the number of participants who have diagnosis of DILI who report pruritus (itching) compared to the number with other acute non-DILI conditions (e.g. autoimmune hepatitis/viral hepatitis) who report itching within a cohort of patients presenting with acute liver injury.
4 secondary outcomes
Duration of itching (pruritus) in patients who present with acute liver injury
Time frame: 4 years
Severity of itching (pruritus) in patients who present with acute liver injury
Time frame: 4 years
Genetic variants associated with itching (pruritus) in patients who present with acute liver injury
Time frame: 2.5 years
Health status reported by patients who present with acute liver injury
Time frame: 4 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Background: PubMed 21544079Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, Wilke RA, Avigan M, Kaplowitz N, Bjornsson E, Daly AK. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther. 2011 Jun;89(6):806-15. doi: 10.1038/clpt.2011.58. Epub 2011 May 4.
- Background: PubMed 31439850Andrade RJ, Chalasani N, Bjornsson ES, Suzuki A, Kullak-Ublick GA, Watkins PB, Devarbhavi H, Merz M, Lucena MI, Kaplowitz N, Aithal GP. Drug-induced liver injury. Nat Rev Dis Primers. 2019 Aug 22;5(1):58. doi: 10.1038/s41572-019-0105-0.
- Background: PubMed 23419359Bjornsson ES, Bergmann OM, Bjornsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013 Jun;144(7):1419-25, 1425.e1-3; quiz e19-20. doi: 10.1053/j.gastro.2013.02.006. Epub 2013 Feb 16.
- Background: PubMed 35899490Bjornsson ES, Stephens C, Atallah E, Robles-Diaz M, Alvarez-Alvarez I, Gerbes A, Weber S, Stirnimann G, Kullak-Ublick G, Cortez-Pinto H, Grove JI, Lucena MI, Andrade RJ, Aithal GP. A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry. Liver Int. 2023 Jan;43(1):115-126. doi: 10.1111/liv.15378. Epub 2022 Aug 15.
- Background: PubMed 30366773Chen HL, Li HY, Wu JF, Wu SH, Chen HL, Yang YH, Hsu YH, Liou BY, Chang MH, Ni YH. Panel-Based Next-Generation Sequencing for the Diagnosis of Cholestatic Genetic Liver Diseases: Clinical Utility and Challenges. J Pediatr. 2019 Feb;205:153-159.e6. doi: 10.1016/j.jpeds.2018.09.028. Epub 2018 Oct 23.
- Background: PubMed 30926241European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol. 2019 Jun;70(6):1222-1261. doi: 10.1016/j.jhep.2019.02.014. Epub 2019 Mar 27.
- Background: PubMed 26346867Fontana RJ, Hayashi PH, Barnhart H, Kleiner DE, Reddy KR, Chalasani N, Lee WM, Stolz A, Phillips T, Serrano J, Watkins PB; DILIN Investigators. Persistent liver biochemistry abnormalities are more common in older patients and those with cholestatic drug induced liver injury. Am J Gastroenterol. 2015 Oct;110(10):1450-9. doi: 10.1038/ajg.2015.283. Epub 2015 Sep 8.
- odevixibat descriptionLink provided by the sponsor.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug Induced Liver Injury and Pruritus, run by University of Nottingham at 1 site in United Kingdom.
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 6 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 27 Jul 2026. 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 United Kingdom. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elinor Study Coordinator (0115 7484390, Elinor.Cross@nottingham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of pruritus (itching) in patients with DILI (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06446609, which also lists 7 linked publications.
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 27 Jul 2026.