Clinical trial NCT05479721: LITMUS Imaging Study
Official title: Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & Validation of Imaging Modality Performance Across the NAFLD Spectrum in a Prospectively Recruited Cohort
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: NAFLD
NASH
NASH - Nonalcoholic Steatohepatitis
Fibrosis, Liver
Steatosis of Liver
Keywords: Liver MultisScan
Magnetic Resonance Elastography
Magnetiic Resonance Imaging
deMILI
diffusion weighted imaging
proton density fat fraction
PDFF
iron corrected T1
cT1
liver stiffness
MRI
MRE
diagnostic study
LITMUS
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Newcastle University
name: University of Nottingham
name: University of Cambridge
name: University of Seville
name: Pinnacle Clinical Research, PLLC
name: ICAN Nutrition Education and Research
name: Assistance Publique - Hôpitaux de Paris
name: University of Angers
name: University of Palermo
name: University of Turin, Italy
name: University Medical Center Mainz
name: University of Helsinki
name: University of Bern
name: Linkoeping University
name: Perspectum
name: Antaros Medical
name: Resoundant Inc
name: Pfizer
name: Novartis
name: Takeda
name: Intercept Pharmaceuticals
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Boehringer Ingelheim
First posted: 2022-07-29
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with known or suspected NAFLD who are undergoing liver biopsy as part of their routine clinical care and are already participating in the European NAFLD Registry

Brief summary: The LITMUS Imaging Study is a prospectively recruited, observational study of patients with histologically characterised non-alcoholic fatty liver disease (NAFLD). It aims to evaluate the diagnostic performance of imaging biomarkers (ultrasound elastography and magnetic resonance biomarkers) against NAFLD histological scores in a cross-sectional analysis and the natural history of NAFLD in a longitudinal study.

Detailed description: The LITMUS Imaging study is a non-interventional, observational study conducted in parallel to the European NAFLD Registry (NCT04442334), collecting cross-sectional and longitudinal ultrasound elastography and magnetic resonance elastography and imaging data. The LITMUS Imaging study recruits patients with NAFLD who are having a clinically indicated liver biopsy and are already participating in the European NAFLD Registry. Patients in the LITMUS Imaging study have additional imaging assessments at baseline (within 100 days of baseline liver biopsy) and 2 years after baseline (no follow-up biopsy necessary). Imaging assessments include point shear wave elastography, 2D shear wave elastography, MRI scans (Liver Multiscan, deMILI, diffusion weighted imaging, proton density fat fraction, T1 mapping) and MR elastography. Link-anonymised magnetic resonance data are uploaded to a central online portal and analysed centrally by 4 imaging core labs provided by Perspectum (Liver Multiscan), Antaros Medical (MR elastography and DWI), Resoundant (vendor specific PDFF) and University of Seville (deMILI).

Eligibility criteria: Inclusion Criteria:

1. Recruited to the European NAFLD Registry
2. Patient had a liver biopsy less than 3 months prior to enrolment into the study or is having a liver biopsy in less than 3 months' time for the assessment of NAFLD.
3. Participant is willing and able to give informed consent for participation in the study.

Exclusion Criteria:

1. Patients that do not speak the language in which the patient information is written will be excluded. Due to the nature of the study, being able to read the information about the study or access to a relevant interpreter is a necessary criterion for participant's safety in regards to MR scanning.
2. Patients judged by the investigator to be unsuitable for inclusion in the study (e.g. where the investigator feels that the participant will not be able to comply with the study procedures)
3. Any contra-indication to Magnetic Resonance Imaging (MRI) (e.g. ferrous metal implants/fragments, implantable cardiac defibrillator or permanent pacemaker, metal clips following neurosurgery, pregnancy, other condition that would make MR scanning unsafe in the opinion of the scanner operator)

Primary outcomes:
measure: Diagnostic accuracy of imaging biomarkers for severity of liver fibrosis on histology as reference standard
timeFrame: baseline
Secondary outcomes:
measure: Diagnostic accuracy of imaging biomarkers for diagnosis of NASH on histology as reference standard
timeFrame: baseline
measure: Diagnostic accuracy of imaging biomarkers for histologically assessed fat and iron deposition as reference standard
timeFrame: baseline
measure: To study the natural history of NAFLD and how this may impact prognosis
timeFrame: evaluation of biomarkers at baseline and after 2 years
measure: To evaluate reproducibility and observer dependent variability in reporting of liver imaging biomarkers
timeFrame: evaluation of biomarkers within 30 days
measure: To identify physiological factors that confound the performance of imaging biomarkers for the assessment of fibrosis
timeFrame: baseline
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Angers
country: France
facility: Le Centre de Recherche Clinique (CRC) du CHU d'Angers
city: Paris
country: France
facility: Institut ICAN - Institute of Cardiometabolism And Nutrition Hôpital de la Pitié Salpêtrière
city: Mainz
country: Germany
facility: UNIVERSITÄTSMEDIZIN der Johannes Gutenberg Universität Mainz
city: Würzburg
country: Germany
facility: Universitätsklinikums Würzburg
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Palermo
country: Italy
facility: Università di Palermo
city: Torino
country: Italy
facility: Department of Medical Sciences University of Torino
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Sevilla
country: Spain
facility: Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital
city: Valladolid
country: Spain
facility: HU Clínico de Valladolid
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Bern
country: Switzerland
facility: Inselspital, University Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
city: Nottingham
country: United Kingdom
facility: Queens Medical Centre
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: University of Oxford
name: Michael Pavlides, MBBS, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pavlides M, Mozes FE, Akhtar S, Wonders K, Cobbold J, Tunnicliffe EM, Allison M, Godfrey EM, Aithal GP, Francis S, Romero-Gomez M, Castell J, Fernandez-Lizaranzu I, Aller R, Gonzalez RS, Agustin S, Pericas JM, Boursier J, Aube C, Ratziu V, Wagner M, Petta S, Antonucci M, Bugianesi E, Faletti R, Miele L, Geier A, Schattenberg JM, Tilman E, Ekstedt M, Lundberg P, Berzigotti A, Huber AT, Papatheodoridis G, Yki-Jarvinen H, Porthan K, Schneider MJ, Hockings P, Shumbayawonda E, Banerjee R, Pepin K, Kalutkiewicz M, Ehman RL, Trylesinksi A, Coxson HO; LITMUS Consortium Investigators; Martic M, Yunis C, Tuthill T, Bossuyt PM, Anstee QM, Neubauer S, Harrison S. Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol. Contemp Clin Trials. 2023 Nov;134:107352. doi: 10.1016/j.cct.2023.107352. Epub 2023 Oct 4.