Clinical trial NCT03289897: Non-invasive Rapid Assessment of NAFLD Using Magnetic Resonance Imaging With LiverMultiScan
Official title: Non-invasive Rapid Assessment of Non-alcoholic Fatty Liver Disease (NAFLD) Using Magnetic Resonance Imaging With LiverMultiScan (RADIcAL1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: NASH - Nonalcoholic Steatohepatitis
NAFLD
Metabolic Syndrome
Lead sponsor: Perspectum
Sponsor class: INDUSTRY
Collaborators: name: University of Coimbra
name: University Hospital Ulm
name: Leiden University Medical Center
name: Liverpool University Hospitals NHS Foundation Trust
name: University Hospital Southampton NHS Foundation Trust
name: King's College Hospital NHS Trust
name: NHS Greater Glasgow and Clyde
name: Glasgow Royal Infirmary
name: Ninewells Hospital
name: Royal Infirmary of Edinburgh
name: St George's University Hospitals NHS Foundation Trust
First posted: 2017-09-21
Enrollment: 801
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: A multi-centre randomised controlled trial to determine the implementation and health care cost of LiverMultiScan vs. routine methodical assessment (standard care) of Non-alcoholic fatty liver disease (NAFLD) across several European countries.

Detailed description: Non-alcoholic fatty liver disease (NAFLD) is a condition associated with obesity, insulin resistance and heart disease. Research has shown that fatty liver (steatosis) can lead to a spectrum of diseases including low grade inflammation (steatohepatitis or non-alcoholic steatohepatitis (NASH)), cirrhosis or liver failure.

The current method used to diagnose liver dysfunction and failure is with percutaneous liver biopsy. This is painful and is not without risk, as the liver is a highly vascular organ. Even with ultrasound guidance, it carries a 1:1000 risk of serious adverse events (e.g. bleeding, infection, bowel perforation). As a result of these factors, liver biopsy is not used in all patients with suspected NAFLD/ NASH unless moderate to severe liver disease is presented or other liver disease need to be excluded. Various diagnostic pathways have arisen, but in the absence of a clearly non-invasive discriminatory test that can stratify normal liver, simple steatosis, steatohepatitis and cirrhosis, there is no standardised pathway.

LiverMultiScan has been tested against liver biopsy and has been shown to be the first imaging test that can identify early liver disease and predict clinical outcomes accurately. LiverMultiScan has recently been CE-Marked and FDA-cleared, so is available for clinical use, but as a new test, it is not yet widely established in clinical practice. This study will utilise LiverMultiScan and see if it can be the basis of a viable diagnostic pathway in EU healthcare systems by adopting it in different EU countries, and determining the economic costs and benefits.

Eligibility criteria: Inclusion Criteria:

* Male and female patients aged 18-75 years, due to undergo evaluation for suspected non-alcoholic fatty liver disease
* Presence of:

  * elevated liver function tests (ALT, AST or GGT ≥ 1.5 x upper limit of normal and ≤ 5 x upper limit of normal)

OR

* imaging suggestive of Fatty liver disease.

OR

Presence of ≥ 3 of the following criteria:

1. insulin resistance or type 2 diabetes mellitus
2. obesity (BMI \> 30 or waist-to-hip ratio \> 1.00 for men / \> 0.85 for women)
3. hypertension (≥ 130/85 mmHg)
4. elevated triglycerides (≥ 1.7 mmol/l)
5. low HDL-cholesterol (\< 1.05 mmol/l for men / \< 1.25 mmol/l for women)

   * Participant is willing and able to give informed consent for participation in the study.

Exclusion Criteria:

* The participant may not enter the study if they have any contraindication to magnetic resonance imaging (inc pregnancy, extensive tattoos, pacemaker, shrapnel injury, severe claustrophobia).
* Patients with proven liver disease other than NAFLD.
* Liver transplantation
* Patients that present with clinical signs of chronic liver failure (variceal bleeding, ascites, overt encephalopathy)
* Pregnancy
* Alcohol over-use/ abuse as determined by local guidelines
* Patient with known malignant liver tumours and those with any malignancy with life expectancy \< 36 months
* Heart failure NYHA stages II-IV
* Severe mental illness
* Any other cause, including a significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study

Primary outcomes:
measure: To investigate whether the introduction of LiverMultiScan as a standardised diagnostic test for liver disease can prove a cost-effective method in different EU territories.
timeFrame: 1 year
Secondary outcomes:
measure: Patient satisfaction: questionnaire
timeFrame: 1 year
measure: Certainty of diagnosis
timeFrame: 1 year
measure: Frequency of diagnosis
timeFrame: 1 year
measure: Time to diagnosis
timeFrame: 1 year
measure: Measure resource use
timeFrame: 1 year
measure: Cost effectiveness of LiverMultiScan
timeFrame: 1 year
measure: Personnel skills required for diagnosis
timeFrame: 1 year
Other outcomes:
Locations:
city: Ulm
country: Germany
facility: University Hospital Ulm
state: Baden-Württemberg
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South Holland
city: Coimbra
country: Portugal
facility: University of Coimbra
state: Centro
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
state: Hampshire
city: Liverpool
country: United Kingdom
facility: Aintree Hospital
state: Merseyside
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: St George's Hospital
Study officials:
affiliation: University Hospital Ulm
name: Matthias Dollinger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Perspectum Diagnostics
name: Dimitar Tonev, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Banerjee R, Pavlides M, Tunnicliffe EM, Piechnik SK, Sarania N, Philips R, Collier JD, Booth JC, Schneider JE, Wang LM, Delaney DW, Fleming KA, Robson MD, Barnes E, Neubauer S. Multiparametric magnetic resonance for the non-invasive diagnosis of liver disease. J Hepatol. 2014 Jan;60(1):69-77. doi: 10.1016/j.jhep.2013.09.002. Epub 2013 Sep 12.
citation: Pavlides M, Banerjee R, Sellwood J, Kelly CJ, Robson MD, Booth JC, Collier J, Neubauer S, Barnes E. Multiparametric magnetic resonance imaging predicts clinical outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. doi: 10.1016/j.jhep.2015.10.009. Epub 2015 Nov 10.
citation: Tonev D, Shumbayawonda E, Tetlow LA, Herdman L, French M, Rymell S, Thomaides-Brears H, Caseiro-Alves F, Castelo-Branco M, Ferreira C, Coenraad M, Lamb H, Beer M, Kelly M, Banerjee R, Dollinger M; RADIcAL1. The Effect of Multi-Parametric Magnetic Resonance Imaging in Standard of Care for Nonalcoholic Fatty Liver Disease: Protocol for a Randomized Control Trial. JMIR Res Protoc. 2020 Oct 26;9(10):e19189. doi: 10.2196/19189.