Condition category
Digestive System
Date applied
28/10/2019
Date assigned
18/11/2019
Last edited
18/11/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Methotrexate is a drug widely prescribed, however the most appropriate method of monitoring is debated and currently unclear, demonstrated by divergent guidelines across specialities. Historically concerns have been raised regarding methotrexate and the development of liver fibrosis; more recent publications have cast doubt upon this potential relationship.

The discovery of novel, non-invasive methods to assess liver fibrosis, such as transient elastography (e.g. FibroScan®) have allowed fresh consideration into this difficult area.

This study aims to assess the prevalence of liver fibrosis (by way of FibroScan®, blood tests and clinician review) in participants who are taking methotrexate, compared with those who have never taken this drug.

Who can participate?
Patients aged over 18 who are have been taking methotrexate for six months or more, and age matched controls who have never taken methotrexate

What does the study involve?
Risk factors for liver fibrosis will be assessed for each participant e.g. presence of diabetes mellitus, BMI and body mass composition, current and previous alcohol use, cumulative dose and duration of methotrexate use etc.

What are the possible benefits and risks of participating?
Possible benefits of taking part in this research include the health checks included as part of it, which you are informed at the time. For the majority of people, these health checks are very reassuring. Should any abnormalities be found then referral for appropriate assessment and investigations will be undertaken.
The culmination of this research should better inform clinicians about risk factors for potential liver injury in those individuals taking methotrexate, and help to shape future guidelines.
There is a possibility that the health checks performed show up a problem. In this circumstance, patients would be informed immediately and the next appropriate steps will be organised and made clear. We appreciate the discovery of health-related findings can cause worry and the staff are on hand to discuss any concerns

Where is the study run from?
York Hospital (UK)

When is the study starting and how long is it expected to run for?
From June 2019 to September 2020

Who is funding the study?
LIVErNORTH (UK)

Who is the main contact?
Dr Lucy Turner, lucy.turner7@nhs.net
lucy.turner7@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Dr Lucy Turner

ORCID ID

Contact details

Hepatology Department
York Hospital
Wigginton Road
York
YO31 8HE
United Kingdom
+44 (0)1904 725467
lucy.turner7@nhs.net

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

42142

Study information

Scientific title

A study to investigate the liver function of patients taking methotrexate, and risk-stratify them accordingly

Acronym

Study hypothesis

There is no difference in the prevalence of liver fibrosis between individuals taking methotrexate, compared with those who are not

Ethics approval

Approved 18/06/2019, NHS HRA (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH), ref: 19/NE/0176

Study design

Non-randomized; Observational; Design type: Validation of investigation /therapeutic procedures

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Liver fibrosis

Intervention

Participants will be recruited largely from rheumatology and dermatology outpatient clinics in York and Scarborough Hospitals. Over the 12 month study period we will aim to recruit 698 patients. Controls will be matched by age and gender. Risk factors for liver fibrosis will be assessed for each participant e.g. presence of diabetes mellitus, BMI and body mass composition, current and previous alcohol use, cumulative dose and duration of methotrexate use etc.

The following things will be undertaken for each study participant:
a) Electronic record
The PI will evaluate historical data from the patient electronic record; including blood test results, duration and cumulative dose of MTX prescribed (if relevant), patient demographic data such as postcode, age and gender. The data will be recorded in an EXCEL file, with no patient identifiable factors. All information will be kept on an encrypted password protected York NHS Trust IT system.
b) Participant questionnaire
Participants will be asked to complete a lifestyle questionnaire. This will be anonymous; they will be given adequate time and assisted for any special needs as appropriate. The questionnaire focusses on patients' understanding and knowledge of methotrexate. The answers are in both qualitative and quantitative fashion. Answers will be compiled, cumulated and analysed.
c) Participant history and special tests
This part of the study will be largely completed by the PI. Participants will be reviewed in an outpatient environment. Participants will receive an Invite Letter and Participant Information Sheet through the post. Participants can either contact the research team in advance to make a mutually agreeable time to meet, or they can meet a member of the research team on the day of their existing outpatient appointment. The research member conducting the review will go through the questions detailed in the proforma. These questions are based on the participants' medical history, medications and alcohol intake - both historical and current. The research team member will go on to perform a liver Fibroscan® and body mass composite score. If blood tests have not been performed for the last three months, then the research member will request bloods (in keeping with current guidance). This information will be recorded onto an anonymised sheet.

Following the interview these sheets will be manually inserted onto a larger, anonymised database, also kept on an encrypted password-protected York NHS Trust IT system linked computer. When inserting the individuals' dataset onto the spreadsheet the information will be coded, for the ease of data analysis.

A patient group was involved in the compilation of the research methodology. Following their feedback alteration was undertaken to the consent form, participant information leaflet, invite letter, questionnaire, and posters for the research study.

The proposed sample size for this project is a total of 698 participants - 349 in each arm. This power calculation was calculated using existing data suggesting that the prevalence of liver fibrosis in patients taking methotrexate is reported as 5%, and the prevalence of liver fibrosis in patients not taking methotrexate as 1.3% in the UK population. This study uses a case control ratio of 1:1 and assumes a power of 80%.

Participant Journey:
From a participant point of view the following summarises their proposed progress through the study:
1) Receipt of a Participant Information Sheet and Invite Letter for study, with their pre-existing planned outpatient appointment.
2) Immediately after attendance at there planned outpatient appointment, they will have the opportunity to be recruited into the study which includes the following:
- Consent process
- Lifestyle questionnaire
- Medical history questions
- FibroScan®
- Body mass composition measurement
This will take approximately 30 minutes. Following this the participants' involvement in the study is complete. No additional visits or follow-up is required

Intervention type

Other

Phase

Drug names

Primary outcome measure

Presence of liver fibrosis (by liver Fibroscan®)

Secondary outcome measures

Risk factors for liver fibrosis will be assessed for each participant e.g. presence of diabetes mellitus, BMI and body mass composition, current and previous alcohol use, cumulative dose and duration of methotrexate use etc.

Overall trial start date

03/09/2018

Overall trial end date

04/09/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Individuals in the Methotrexate cohort must have taken this medication for at least 6 months
2. All participants must be over 18 years old

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 698; UK Sample Size: 698

Participant exclusion criteria

1. Pregnant females
2. Previously taken Methotrexate, but are no longer currently taking it
3. Lack capacity to consent

Recruitment start date

25/06/2019

Recruitment end date

25/06/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

York Hospital
Wigginton Road
York
YO31 8HE
United Kingdom

Sponsor information

Organisation

York Teaching Hospital NHS Foundation Trust

Sponsor details

York Hospital
Wigginton Road
York
YO31 8HE
United Kingdom
+44 (0)1904725123
deborah.phillips@york.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

LIVErNORTH

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Name: Lucy Turner
Email: lucy.turner7@nhs.net
Consent from participants was obtained for this sharing of data
All data will be completely anonymised
Data will be available from completion of study (25/06/20) for 1 year
Type of data:
1. Participant age
2. Height
3. Weight
4. BMI
5. Ethnicity
6. Gender
7. MTX cumulative dose (if appropriate)
8. other mediations
9. comorbidities
10. FibroScan result
11. Alcohol consumption (units per week)
12. Audit C score

Intention to publish date

04/09/2021

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

28/10/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR)