Assessment of itch symptoms in primary sclerosing cholangitis and other chronic liver diseases

ISRCTN	ISRCTN15518794
DOI	https://doi.org/10.1186/ISRCTN15518794
ClinicalTrials.gov (NCT)	Nil known
Clinical Trials Information System (CTIS)	Nil known
Integrated Research Application System (IRAS)	305983
Protocol serial number	IRAS 305983
Sponsor	University of Birmingham
Funder	GlaxoSmithKline

Submission date: 09/02/2023
Registration date: 20/02/2023
Last edited: 17/01/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Primary sclerosing cholangitis (PSC) is a disease that causes inflammation and scarring of the bile ducts. There are no medicines that have been shown to slow down the rate of liver damage, and liver transplantation is the only life-saving treatment for people with the disease.
Whilst many clinical trials are underway, few address the symptoms of the disease. In a survey led by the international charity PSC Support, itching (pruritus) was named as one of the symptoms that impacted quality of life the most. However, there is no published study so far which indicates how this symptom varies according to the natural history of the disease, or according to currently available anti-itch medicines.
The aim of this study is to obtain detailed information on the presence and impact of itch symptoms in people who have the liver condition primary sclerosing cholangitis and compare this with itch symptoms in other chronic liver diseases, in those with inflammatory bowel disease (IBD) alone and in healthy participants. The researchers will investigate if there are any links between itch symptoms and the severity of the liver disease and blood test results. The variability of itch symptoms over a 48-week period will also be observed, along with the impact itch has on quality of life.

Who can participate?
Essentially any person with the liver condition known as primary sclerosing cholangitis can participate in the PSC group. The comparison group will be those with certain other chronic liver diseases, IBD alone and healthy participants. All participants should be aged over 16 years.

What does the study involve?
Participation involves completing four or five health-related questionnaires; two exploring itch symptoms and two exploring quality of life. For the PSC group an additional specific health-related questionnaire will be completed). If blood testing is required as per routine care, there will be additional testing to measure certain biomarkers that may be linked to itch. This data will be collected 2-4 times over a 48-week period.

What are the possible benefits and risks of participating?
Results from this study may help us to better understand why those with liver disease experience itch symptoms. This may therefore result in improved treatments and management of this in the future. The only real disadvantage of taking part in this study will be the extra time it will take to complete the surveys. The researchers have tried to make the questionnaires; relevant, simple and easy to complete. They estimate it should take about 10 minutes in total to complete.

Where is the study run from?
The University of Birmingham (UK)

When is the study starting and how long is it expected to run for?
July 2021 to April 2025

Who is funding the study?
GlaxoSmithKline (UK)

Who is the main contact?
Dr Nasir Hussain, nxh100@student.bham.ac.uk

Contact information

Dr Nasir Hussain
Principal investigator

Liver Unit
Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2GW
United Kingdom

Phone	+44 (0)7877427846
Email	nxh100@student.bham.ac.uk

Study information

Primary study design	Observational
Study design	Mulit-centre observational cohort study with cross-sectional and prospective elements
Secondary study design	Cohort study
Study type	Participant information sheet
Scientific title	Characterising the burden and clinical trajectory of pruritus in primary sclerosing cholangitis and non-cholestatic chronic liver disease
Study objectives	To quantify the severity and variability of itch symptoms in people living with the disease primary sclerosing cholangitis (PSC) and evaluate how this compares with non cholestatic chronic liver disease, inflammatory bowel disease (IBD) alone and healthy participants.
Ethics approval(s)	Approved 28/10/2021, North of Scotland Research Ethics Committee (Summerfield House, 2 Eday Road, Aberdeen, AB15 6RE, UK; +44 (0)1224 558458; gram.norses@nhs.scot), ref: RG_21-051
Health condition(s) or problem(s) studied	Pruritus in primary sclerosing cholangitis, non-cholestatic chronic liver disease, inflammatory bowel disease
Intervention	There will be data collection in the form of health-related questionnaires. These will include questionnaires exploring pruritus and quality of life. Participants' medical record data will also be collected to assess for any correlations between their disease and pruritus. Routine blood test results will be collected as well as particular blood markers that may be associated with pruritus. This data will be collected at different time points over a 48-week period.
Intervention type	Other
Primary outcome measure(s)	Exploratory primary outcome: The prevalence and long-term variability of pruritus over 48 weeks in patients with primary sclerosing cholangitis. Pruritus is measured using the numerical rating scale (NRS), 5d itch scale and the Simple Cholestatic Complaints Score at baseline, 12, 24, 36 and 48 weeks.
Key secondary outcome measure(s)	1. The variability and intensity of pruritus in PSC, compared with pruritus in non-cholestatic liver diseases, IBD alone and healthy participants. Pruritus is measured using the NRS and 5d itch tool at baseline, 12, 24, 36 and 48 weeks for PSC and measured at baseline and 48 weeks for non-cholestatic liver disease, and measured at baseline only for those with IBD alone and healthy participants. 2. Severity and extent of the liver disease, collected from medical records at baseline and up until 48 weeks 3. Routinely collected laboratory blood tests (full blood count, renal function, liver function tests, HbA1C and INR test results) collected during routine clinic visits from baseline up until 48 weeks 4. Exploratory biomarkers (serum bile acid levels and autotaxin activity results) collected during routine clinic visits from baseline and up until 48 weeks 5. Current use of anti-pruritic therapies and their effectiveness, collected from medical records at baseline up until 48 weeks 6. Quality of life measures measured using the Chronic Liver Disease Questionnaire CLDQ and the EQ-5D-5L tools, taken at baseline, 12, 24, 36 and 48 weeks for those with PSC, baseline and 48 weeks for those with non-cholestatic liver disease, and at baseline for those with IBD alone and healthy controls.
Completion date	01/04/2025

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	16 Years
Sex	All
Target sample size at registration	800
Key inclusion criteria	For the PSC group: 1. Must have a diagnosis of PSC 2. Either, subjects attending liver medicine clinic; or registered participants within the nationwide UK-PSC study Non PSC group: 1. Subjects attending the liver or gastroenterology medicine clinic or healthy participants (no present or previous diagnosis of liver disease or IBD) 2. Diagnosis of following liver diseases; metabolic/non-alcoholic fatty liver disease, alcohol induced liver disease, chronic viral hepatitis, drug-induced liver disease, autoimmune hepatitis, genetic disorders of cholestasis 3. Diagnosis of IBD 4. Healthy participants who have no present or previous diagnosis of liver disease or inflammatory bowel disease
Key exclusion criteria	PSC group: 1. Age <16 years 2. Women who are pregnant or lactating 3. Lack of capacity (as deemed by the investigator) to provide an accurate medical history 4. Not able to communicate in English and no translator available 5. Small duct PSC without concomitant inflammatory bowel disease (IBD) 6. Other causes of chronic liver disease including 6.1. IgG4-related disease 6.2. Primary biliary cholangitis (PBC) 6.3. Secondary sclerosing cholangitis 6.4. Fatty liver disease 6.5. Habitual alcohol consumption greater than 21 oz/week for men or 14 ox/week for women 6.6. HIV infection 6.7. Drug-induced liver disease 6.8. Genetic disorders of cholestasis 6.9. Wilson disease 6.10. Alpha-1-antitrypsin deficiency 6.11. Hepatic veno-occlusive disease, including portal vein thrombosis or Budd-Chiari syndrome 7. History of liver transplantation 8. Current or prior history of cholangiocarcinoma, pancreatic or hepatocellular cancer 9. Gallbladder cancer in the previous 12 months 10. Colorectal cancer (or evidence of active metastatic disease) in the previous twelve months 11. Chemo- or radiotherapy in the previous twelve months 12. Chronic kidney disease, defined by the use of renal replacement therapy or a urea >20 mmol/l Non PSC Group: 1. Age <16 years 2. Women who are pregnant or lactating 3. Lack of capacity (as deemed by the investigator) to provide an accurate medical history 4. Not able to communicate in English and no translator available 5. Radiological evidence of cholangiography including secondary sclerosing cholangitis 6. Histological evidence of inflammatory bile duct lesions or periductal fibrosis 7. Mixed aetiology of liver disease 8. Other causes of chronic liver disease: 8.1. Primary biliary cholangitis (PBC) 8.2. Primary sclerosing cholangitis (PSC) 8.3. HIV infection 8.4. Wilson disease 8.5. Alpha-1-antitrypsin deficiency 8.6. Hepatic veno-occlusive disease, including portal vein thrombosis or Budd-Chiari syndrome 9. History of liver transplantation 10. Current or prior history of cholangiocarcinoma, pancreatic or hepatocellular cancer 11. Gallbladder cancer in the previous 12 months 12. Colorectal cancer (or evidence of active metastatic disease) in the previous twelve months 13. Chemo- or radiotherapy in the previous twelve months 14. Chronic kidney disease, defined by the use of renal replacement therapy or a urea >20 mmol/l 15. Other known dermatological, haematological or extrahepatic disorder, including iatrogenic causes (e.g. excessive opioid use) associated with pruritus; investigator discretion
Date of first enrolment	18/10/2021
Date of final enrolment	01/04/2024

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Royal Free Hospital

Pond Street
London
NW3 2QG
United Kingdom

John Radcliffe Hospital

Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Kings College Hospital

Mapother House
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom

Queen Elizabeth Hospital

Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom

Norfolk and Norwich University Hospital

Colney Lane
Colney
Norwich
NR4 7UY
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data-sharing plans for the current study are unknown and will be made available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Protocol file	version 3.0	01/09/2022	13/02/2023	No	No

Additional files

43193_PROTOCOL_V3.0_01Sep22.pdf: Protocol file

Editorial Notes

17/01/2024: The following changes were made to the study record:
1. Contact details updated.
2. The recruitment end date was changed from 18/10/2023 to 01/04/2024.
3. The overall study end date was changed from 18/10/2024 to 01/04/2025.
13/02/2023: Trial's existence confirmed by the North of Scotland Research Ethics Committee.