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CompletedNCT03289897RADIcAL1Updated Aug 22, 2023

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

An interventional study of LiverMultiScan in NASH - Nonalcoholic Steatohepatitis, NAFLD and Metabolic Syndrome, sponsored by Perspectum. Completed at 11 sites in 4 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-08-22.

Sponsored by Perspectum · Not applicable, Interventional, and Other

Phase
Not applicable
Study type
Interventional
Enrollment
801
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • NASH - Nonalcoholic Steatohepatitis
  • NAFLD
  • Metabolic Syndrome
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
801 participants (actual)

Study arms

  • 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

  • No intervention
    Control Arm

    Standard of care as per guidelines of the local centre

Interventions

  • Diagnostic testLiverMultiScan

    LiverMultiScan is an imaging technique which is able to identify early liver disease.

05

What researchers measure

Primary outcomes

  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.

    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.

    Time frame: 1 year

Secondary outcomes

  1. Patient satisfaction: questionnaire

    Patient feedback from patient satisfaction questionnaire, at baseline, and all follow-up visits to the end of the study.

    Time frame: 1 year

  2. 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.

    Time frame: 1 year

  3. 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.

    Time frame: 1 year

  4. Time to diagnosis

    Time from randomisation to diagnosis by the physician, as recorded at final follow-up visit.

    Time frame: 1 year

  5. Measure resource use

    Rates of liver related outpatient investigations/consultations/hospital admissions per 400 patients during the study.

    Time frame: 1 year

  6. Cost effectiveness of LiverMultiScan

    Cost of LiverMultiScan based on randomised comparison.

    Time frame: 1 year

  7. 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.

    Time frame: 1 year

06

Study locations

11 sites
  • University Hospital Ulm
    Ulm, Baden-Württemberg 89081, Germany
  • Leiden University Medical Center
    Leiden, South Holland 2333, Netherlands
  • University of Coimbra
    Coimbra, Centro 3004-531, Portugal
  • Southampton University Hospital
    Southampton, Hampshire SO16 6YD, United Kingdom
  • Aintree Hospital
    Liverpool, Merseyside L9 7AL, United Kingdom
  • Ninewells Hospital
    Dundee, DD2 1SG, United Kingdom
  • Royal Infirmary of Edinburgh
    Edinburgh, EH16 4SA, United Kingdom
  • Glasgow Royal Infirmary
    Glasgow, G40SF, United Kingdom
  • Queen Elizabeth University Hospital
    Glasgow, G51 4TF, United Kingdom
  • King's College Hospital
    London, SE5 9RS, United Kingdom
  • St George's Hospital
    London, SW170Q2, United Kingdom
07

References and documents

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. PubMed 24036007 ↗
  • 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. PubMed 26471505 ↗
  • 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. PubMed 33104014 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03289897
Lead 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
Responsible party
Sponsor
First posted
Sep 21, 2017
Start date
Sep 5, 2017
Primary completion
Dec 31, 2020
Completion
Dec 31, 2020
Last update
Aug 22, 2023

Study contacts

Matthias Dollinger, MD
principal investigator · University Hospital Ulm
Dimitar Tonev, MD
principal investigator · Perspectum Diagnostics

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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