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

• ClinicalTrials.gov Identifier: NCT03289897
• Recruitment Status: Completed
• First Posted: September 21, 2017
• Last Update Posted: March 4, 2021
• Sponsor: Perspectum
• Collaborators: University of Coimbra; University Hospital Ulm; Leiden University Medical Center; Liverpool University Hospitals NHS Foundation Trust; University Hospital Southampton NHS Foundation Trust; King's College Hospital NHS Trust; NHS Greater Glasgow and Clyde; Glasgow Royal Infirmary; Ninewells Hospital; Royal Infirmary of Edinburgh; St George's University Hospitals NHS Foundation Trust
• Information provided by (Responsible Party): Perspectum

Study Description

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.

Condition or disease	Intervention/treatment	Phase
NASH - Nonalcoholic Steatohepatitis; NAFLD; Metabolic Syndrome	Diagnostic Test: LiverMultiScan	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 801 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Non-invasive Rapid Assessment of Non-alcoholic Fatty Liver Disease (NAFLD) Using Magnetic Resonance Imaging With LiverMultiScan (RADIcAL1)
• Actual Study Start Date: September 4, 2017
• Actual Primary Completion Date: December 31, 2020
• Actual Study Completion Date: December 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 1 year ]
   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.

Secondary Outcome Measures :

1. Patient satisfaction: questionnaire [ Time Frame: 1 year ]
   Patient feedback from patient satisfaction questionnaire, at baseline, and all follow-up visits to the end of the study.
2. Certainty of diagnosis [ Time Frame: 1 year ]
   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.
3. Frequency of diagnosis [ Time Frame: 1 year ]
   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.
4. Time to diagnosis [ Time Frame: 1 year ]
   Time from randomisation to diagnosis by the physician, as recorded at final follow-up visit.
5. Measure resource use [ Time Frame: 1 year ]
   Rates of liver related outpatient investigations/consultations/hospital admissions per 400 patients during the study.
6. Cost effectiveness of LiverMultiScan [ Time Frame: 1 year ]
   Cost of LiverMultiScan based on randomised comparison.
7. Personnel skills required for diagnosis [ Time Frame: 1 year ]
   Percentage of total consultations performed by a specialist, at each specialist medical category, from date of randomisation to end of study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

University Hospital Ulm

Ulm, Baden-Württemberg, Germany, 89081

Netherlands

Leiden University Medical Center

Leiden, South Holland, Netherlands, 2333

Portugal

University of Coimbra

Coimbra, Centro, Portugal, 3004-531

United Kingdom

Southampton University Hospital

Southampton, Hampshire, United Kingdom, SO16 6YD

Aintree Hospital

Liverpool, Merseyside, United Kingdom, L9 7AL

Ninewells Hospital

Dundee, United Kingdom, DD2 1SG

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom, EH16 4SA

Glasgow Royal Infirmary

Glasgow, United Kingdom, G40SF

Queen Elizabeth University Hospital

Glasgow, United Kingdom, G51 4TF

King's College Hospital

London, United Kingdom, SE5 9RS

St George's Hospital

London, United Kingdom, SW170Q2

Sponsors and Collaborators

Perspectum

University of Coimbra

University Hospital Ulm

Leiden University Medical Center

Liverpool University Hospitals NHS Foundation Trust

University Hospital Southampton NHS Foundation Trust

King's College Hospital NHS Trust

NHS Greater Glasgow and Clyde

Glasgow Royal Infirmary

Ninewells Hospital

Royal Infirmary of Edinburgh

St George's University Hospitals NHS Foundation Trust

Investigators

• Principal Investigator: Matthias Dollinger, MD; University Hospital Ulm
• Principal Investigator: Dimitar Tonev, MD; Perspectum Diagnostics

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Perspectum
• ClinicalTrials.gov Identifier: NCT03289897
• Other Study ID Numbers: PJM124
• First Posted: September 21, 2017
• Last Update Posted: March 4, 2021
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Fatty Liver; Non-alcoholic Fatty Liver Disease; Metabolic Syndrome; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Liver Diseases; Digestive System Diseases