Drug-induced Liver Injury: Itching Study

NCT06446609 | Recruiting

• 1 other identifier: 23056
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Pruritus; Drug Induced Liver Injury

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (4)

• Duration of itching (pruritus) in patients who present with acute liver injury

  4 years

• Severity of itching (pruritus) in patients who present with acute liver injury

  4 years

• Genetic variants associated with itching (pruritus) in patients who present with acute liver injury

  2.5 years

• Health status reported by patients who present with acute liver injury

  4 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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).

You may not qualify if:

• Patients with comorbidities of eczema and urticaria associated with pruritus
• Patients with existing diagnosis of blood-borne viral hepatitis infection (Hepatitis B/C/E)

Sponsors & Collaborators

• University of Nottingham: lead
• Ipsen: collaborator
• National Institute for Health Research, United Kingdom: collaborator
• Nottingham University Hospitals NHS Trust: collaborator

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

RECRUITING

Related Publications (7)

• 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.

  PMID: 21544079 BACKGROUND

• Andrade 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.

  PMID: 31439850 BACKGROUND

• Bjornsson 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.

  PMID: 23419359 BACKGROUND

• Bjornsson 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.

  PMID: 35899490 BACKGROUND

• Chen 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.

  PMID: 30366773 BACKGROUND

• European 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.

  PMID: 30926241 BACKGROUND

• Fontana 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.

  PMID: 26346867 BACKGROUND

Related Links

• odevixibat description

MeSH Terms

Conditions

Chemical and Drug Induced Liver Injury; Pruritus

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Elinor Study Coordinator

CONTACT

0115 7484390; Elinor.Cross@nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: June 6, 2024
• Study Start: June 30, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2025-06

Locations

GB (1)