Condition category
Digestive System
Date applied
06/04/2020
Date assigned
17/06/2020
Last edited
17/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Psoriasis is a skin condition that causes red, flaky, crusty patches of skin covered with silvery scales. Liver damage is thought to be more common in patients with psoriasis based on previous small studies. Several risk factors are associated with liver disease in this group of patients. This includes severity of psoriasis as inflammation has been linked to liver disease. Other risk factors include alcohol intake and obesity. When psoriasis is not controlled with creams, the first systemic medication of choice is methotrexate. There have been concerns that this medication can lead to liver damage or worsen the liver health of psoriasis patients, but currently there is no strong evidence to confirm this. Several tests are currently used by dermatologists to monitor the liver health of patients with psoriasis. These include blood tests to measure liver enzymes. However, these tests are not very accurate at detecting liver damage. Taking a sample directly from the liver is no longer routinely used to diagnose liver damage as it is invasive and has many risks. A non-invasive scan (Fibroscan) similar to an ultrasound can be used to measure how elastic or stiff the liver is. If the liver is stiff this indicates that some damage has occurred. This test is now increasingly used to diagnose liver damage. This study aims to evaluate the extent of liver scarring in patients with psoriasis and assess the relationship between liver scarring and other potential risk factors for liver damage including methotrexate. In addition, the relationship between the outcome of the Fibroscan and other simple tests such as blood tests and scoring systems currently used for monitoring of liver health will be assessed. The overall aim is to use the information gained from this study to determine the number of participants required for a larger study to investigate factors influencing liver damage in this group of patients and to determine whether or not methotrexate is an important contributor to liver damage. Ultimately a risk prediction model will be built to enable dermatologists to predict the risk of liver fibrosis in patients with psoriasis and more accurately assess which patients are suitable to commence and continue treatment with methotrexate.

Who can participate?
Patients aged 18 and over with chronic plaque psoriasis

What does the study involve?
Participants complete questionnaires, provide blood samples (as part of routine care), undergo measurements of weight, waist, height, blood pressure, and undergo an assessment of liver stiffness using a non-invasive test similar to an ultrasound (a Fibroscan).

What are the possible benefits and risks of participating?
It is known that many patients with psoriasis develop liver disease but it is not known why. Participants will have an assessment of their liver health and will contribute to improving the management of psoriatic liver disease in larger populations of psoriasis patients. Methotrexate is a highly effective, generally safe and highly cost-effective treatment option for psoriasis. In the NHS it is the first choice systemic drug for psoriasis. The ability to accurately predict which patients may be at risk from liver scarring would be advantageous. The outcome of this study will inform the design of the larger study to determine which factors can predict the risk of liver scarring and whether or not methotrexate is an important contributor to the risk of liver scarring. The most effective strategies for monitoring the development of liver scarring in this group of patients can then be determined and the result may help in stratification of treatment in this group of patients based on the risk of developing liver scarring.

Where is the study run from?
The Royal Victoria Infirmary (UK)

When is the study starting and how long is it expected to run for?
January 2019 to June 2022, but this is likely to be extended

Who is funding the study?
Psoriasis Association (UK)

Who is the main contact?
Dr Philip Hampton
Philip.hampton@nhs.net

Trial website

Contact information

Type

Scientific

Primary contact

Dr Philip Hampton

ORCID ID

http://orcid.org/0000-0001-6797-2697

Contact details

Chief Investigator
Newcastle Hospitals NHS Foundation Trust
Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom
+44 (0)191 28 24349
Philip.hampton@nhs.net

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 44694, IRAS 265303

Study information

Scientific title

Investigation of the prevalence of liver fibrosis in patients with psoriasis using transient elastography and evaluation of the relationship between liver fibrosis and risk factors for liver fibrosis including methotrexate

Acronym

Study hypothesis

The prevalence of liver fibrosis in patients with psoriasis is high and unexplained. It is hypothesised that important risk factors such as obesity, alcohol and diabetes contribute to the risk of liver fibrosis more than methotrexate.

Ethics approval

Approved 17/03/2020, North East - Newcastle & North Tyneside 2 Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ; +44 (0)207 104 8091, +44 (0)207 104 8222; newcastlenorthtyneside2.rec@hra.nhs.uk), REC ref: 20/NE/0039

Study design

Observational; Design type: Cross-sectional

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

See additional files

Condition

Liver fibrosis in psoriasis

Intervention

The study will be a cross-sectional design. Patients with chronic plaque psoriasis diagnosed by a dermatologist with a PASI score of at least 5 at any time will be invited to join the study. A patient information leaflet will be provided. Written consent will be obtained.

Data will be collected via questionnaires, from patient’s medical and electronic records. The majority of the data that the researchers are interested in is recorded as part of standard clinical care and they do not want to repeat measurements unnecessarily. They will therefore accept values for blood tests and imaging that have been recorded within 6 months of recruitment to the study. For patient severity scores and assessments of clinical data such as BMI, these will be collected at the time of recruitment.

The following data will be recorded for each patient:
1. Patient demographics: age, gender, ethnicity socioeconomic status
2. Disease severity: duration of psoriasis, age of onset of psoriasis), year of diagnosis (best approximation), year first seen by a dermatologist, Psoriasis Area and Severity Index (PASI) at recruitment, worst ever PASI, Dermatology life Quality Index (DLQI) at recruitment, worst ever DLQI, family history of psoriasis (first degree relative such as parent, sibling or child)
3. Characteristics: height and weight, Body Mass Index (BMI), Waist circumference, smoking status, alcohol intake questionnaire and AUDIT score, blood pressure, skin type and skin cancer risk factors
4. Liver stiffness measurements: value, >7.9kPa (yes/no), > 7kPa (yes/no), > 9.5kPa (yes/no)
5. Alcohol-related questions: AUDIT score, average alcohol intake in the last year (units per day or units per week)*, a history of sustained excessive alcohol consumption of > 35 units/week for females or > 50 units per week for males for more than 1 year, a history of excessive alcohol consumption (>14 units/day for both) – document the average units/day or week and the duration of alcohol, a history of alcohol dependence
6. Comorbidities – has the patient ever had or required treatment for the following illnesses and year of onset of illness:
cardiac disease (heart failure, cardiac arrhythmias, stroke, coronary artery disorders, angina, myocardial infarction), vascular diseases (hypertension, peripheral vascular disorders, deep vein thrombosis, pulmonary embolism, disorders of metabolism and nutrition (diabetes mellitus, impaired glucose tolerance, dyslipidaemia, endocrine diseases (thyroid disease), nervous system disorders(demyelinating diseases, epilepsy), respiratory, thoracic and mediastinal disorders (asthma, COPD), renal and urinary tract diseases (chronic renal failure), hepatobiliary diseases (viral hepatitis infection, other liver disease), gastrointestinal diseases (peptic ulcer), gastrointestinal inflammatory conditions (Crohn's disease, ulcerative colitis), psychiatric diseases (depression, anxiety), infections and infestations (tuberculosis). immune system disorders, skin and soft tissue disorders (psoriatic arthritis (diagnosis of PSA by a rheumatologist? and year of diagnosis), other types of cancers: skin cancers (non-melanoma skin cancer, squamous cell, carcinoma, basal cell carcinoma) melanoma skin cancers and pre-cancerous skin lesions (melanoma skin cancer, melanoma in situ, Bowen disease, actinic keratosis, keratoacanthoma.
7. Duration on methotrexate in months, cumulative dose of methotrexate
8. UV Therapy– (yes/no), duration and type, response
9. Any current systemic drug, Oral PUVA or biologics for psoriasis, Small molecule immunomodulator therapy for psoriasis (apremilast or dimethyl fumarate) – dose, frequency and date started
10. All previous systemic or biologics or oral PUVA, small molecule immunomodulator therapy for psoriasis – start and stop dates and stop reason
11. Any other systemic drug or biologic drugs (dose and frequency) and durations with start dates and stop dates and duration
12. Current medications and start dates – including pimecrolimus or tacrolimus
13. Folic acid: duration and frequency
14. Blood tests: HbA1c, fasting glucose (if available), lipid profile including triglycerides, HDL cholesterol, AST, ALT, abnormal AST in the past year, abnormal ALT in the past year, worst ever AST/ALT, platelets, procollagen three peptide (PIIINP), albumin
15. Previous liver ultrasound report, previous liver biopsy report
16. NAFLD and FIB4 score will be calculated and metabolic syndrome will be assessed based on the IDF metabolic syndrome definition (modified version will be used when fasting results not available (fasting glucose will be replaced by HbAIc and HDL cholesterol and triglyceride will be replaced by non-fasting value)

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Cumulative dose of methotrexate within 6 months of recruitment, calculated from data collected to identify weekly doses each patient received (mg) over time and adding these up to reach a total dose in gram for every patient
2. Liver stiffness measured using Fibroscan within 12 months of recruitment

Secondary outcome measures

1. Demographics, weight (kg), waist (cm), height (cm), blood pressure (mm/Hg) measured at baseline/within 6 months of recruitment
2. Risk factors for liver disease (HbA1c, triglycerides (mmol/L), HDL (mmol/L), LDL (mmol/L), cholesterol (mmol/L), platelets, liver function tests, ALT, worst ever ALT in the past year, AST, worst ever AST in the past year, ALT/AST ratio, albumin, procollagen three peptide (PIIINP) – worst value), measured using blood samples within 6 months of recruitment
3. Psoriasis severity measured using Psoriasis Area Severity Index (PASI) (score ranges: 0-72) at baseline and worst ever
4. Impact of skin disease on the quality of life measured using Dermatology Life Quality Index (DLQI) (score ranges: 0-30) at baseline and worst ever
5. Alcohol use measured using AUDIT Score at baseline and within 6 months of recruitment
6. Metabolic syndrome, defined as waist ≥94 cm (men) or ≥80 cm (women), and ≥2 of:
6.1. ≥5.6 mmol/L (100 mg/dL) or diagnosed diabetes
6.2. <1.0 mmol/L (40 mg/dL) (men); <1.3 mmol/L (50 mg/dL) (women) or drug treatment for low HDL cholesterol
6.3. ≥1.7 mmol/L (150 mg/dL) or drug treatment for high triglycerides
6.4. ≥130/85 mmHg or drug treatment for hypertension
Measured within 6 months of recruitment
7. Liver fibrosis/scarring measured using FIB 4 score within 6 months of recruitment
8. Fatty liver measured using NAFLD score within 6 months of recruitment

Overall trial start date

02/01/2019

Overall trial end date

01/06/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Adults > = 18 years of age
2. Ability to consent
3. Chronic plaque psoriasis diagnosed by a dermatologist with a PASI > = 5 at anytime

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 250; UK Sample Size: 250

Participant exclusion criteria

1. Pregnancy
2. Potential participants who may have difficulties in adequately understanding written or verbal information in English

Recruitment start date

08/06/2020

Recruitment end date

01/03/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Victoria Infirmary
The Newcastle upon Tyne Hospitals NHS Foundation Trust Queen Victoria Road
Newcastle upon Tyne
NE1 4LP
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne Hospitals NHS Foundation Trust

Sponsor details

c/o Sinead Magorrian
Newcastle Joint Research Office
Level 1
Regent Point
Regent Farm Road
Gosforth
Newcastle-upon-Tyne
NE3 3HD
United Kingdom
+44 (0)1912824520
sinead.magorrian@nhs.net

Sponsor type

Hospital/treatment centre

Website

http://www.newcastle-hospitals.org.uk/

Funders

Funder type

Charity

Funder name

Psoriasis Association

Alternative name(s)

The Psoriasis Association

Funding Body Type

private sector organisation

Funding Body Subtype

Other non-profit organizations

Location

United Kingdom

Results and Publications

Publication and dissemination plan

1. Planned publication in peer-reviewed scientific journals
2. Internal report
3. Conference presentation

IPD sharing statement
The datasets generated and/or analysed during the current study will be included in the subsequent results publication. The elements to be public will be in the papers, e.g. as supplementary data.

Intention to publish date

01/06/2023

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

17/06/2020: Uploaded protocol Version 1.2, 26 February 2020 (not peer reviewed). 06/04/2020: Trial's existence confirmed by the NIHR.