Non-invasive Rapid Assessment of NAFLD Using Magnetic Resonance Imaging With LiverMultiScan (RADIcAL1)

Non-invasive Rapid Assessment of Non-alcoholic Fatty Liver Disease (NAFLD) Using Magnetic Resonance Imaging With LiverMultiScan (RADIcAL1)

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; NAFLD; NASH - Nonalcoholic Steatohepatitis
• Intervention / Treatment: Diagnostic test: LiverMultiScan

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.

• Study Type: Interventional
• Enrollment (Actual): 801
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89081
      • University Hospital Ulm
• Netherlands
  • South Holland
    • Leiden, South Holland, Netherlands, 2333
      • Leiden University Medical Center
• Portugal
  • Centro
    • Coimbra, Centro, Portugal, 3004-531
      • University of Coimbra
• United Kingdom
  • Dundee, United Kingdom, DD2 1SG
    • Ninewells Hospital
  • Edinburgh, United Kingdom, EH16 4SA
    • Royal Infirmary of Edinburgh
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • Glasgow, United Kingdom, G40SF
    • Glasgow Royal Infirmary
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, SW170Q2
    • St George's Hospital
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton University Hospital
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L9 7AL
      • Aintree Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Arm-LiverMultiScan; Patients will be scanned using the LiverMultiScan. Follow-up will be determined by the results of the scan.	Diagnostic test: LiverMultiScan; LiverMultiScan is an imaging technique which is able to identify early liver disease.
No Intervention: Control Arm; Standard of care as per guidelines of the local centre

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Proportion of patients with suspected NAFLD incurring liver related hospital consultations and/or liver biopsies, from the date of randomisation to the end of the study follow-up.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient satisfaction: questionnaire	Patient feedback from patient satisfaction questionnaire, at baseline, and all follow-up visits to the end of the study.	1 year
Certainty of diagnosis	Certainty of diagnosis is defined as binary (yes/no vs. unlikely/probable) at baseline and all follow-up visits to the end of the study.	1 year
Frequency of diagnosis	Frequency of diagnosis is defined as binary (yes/probable vs. no/unlikely) at baseline and all follow-up visits to the end of the study.	1 year
Time to diagnosis	Time from randomisation to diagnosis by the physician, as recorded at final follow-up visit.	1 year
Measure resource use	Rates of liver related outpatient investigations/consultations/hospital admissions per 400 patients during the study.	1 year
Cost effectiveness of LiverMultiScan	Cost of LiverMultiScan based on randomised comparison.	1 year
Personnel skills required for diagnosis	Percentage of total consultations performed by a specialist, at each specialist medical category, from date of randomisation to end of study.	1 year

Collaborators and Investigators

• Sponsor: Perspectum
• Collaborators: King's College Hospital NHS Trust; University of Coimbra; Liverpool University Hospitals NHS Foundation Trust; University Hospital Southampton NHS Foundation Trust; Leiden University Medical Center; St George's University Hospitals NHS Foundation Trust; NHS Greater Glasgow and Clyde; University Hospital Ulm; Royal Infirmary of Edinburgh; Glasgow Royal Infirmary; Ninewells Hospital
• Investigators: Principal Investigator: Matthias Dollinger, MD, University Hospital Ulm; Principal Investigator: Dimitar Tonev, MD, Perspectum Diagnostics

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2017
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 18, 2017
• First Posted (Actual): September 21, 2017

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Liver Diseases; Insulin Resistance; Hyperinsulinism; Fatty Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: PJM124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No