LITMUS Imaging Study

NAFLD Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05479721
• Other study ID #: IRAS ID 250344
• Secondary ID: 18/LO/1953
• Status: Active, not recruiting
• Start date: September 4, 2019
• Est. completion date: October 31, 2024

Study information

• Verified date: November 2023
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 450
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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)

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis, Liver
• Liver Cirrhosis
• NAFLD
• NASH
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease
• Steatosis of Liver

Locations

Country	Name	City	State
Finland	Helsinki University Hospital	Helsinki
France	Le Centre de Recherche Clinique (CRC) du CHU d'Angers	Angers
France	Institut ICAN - Institute of Cardiometabolism And Nutrition Hôpital de la Pitié Salpêtrière	Paris
Germany	UNIVERSITÄTSMEDIZIN der Johannes Gutenberg Universität Mainz	Mainz
Germany	Universitätsklinikums Würzburg	Würzburg
Greece	Laiko General Hospital of Athens	Athens
Italy	Università di Palermo	Palermo
Italy	Department of Medical Sciences University of Torino	Torino
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital	Sevilla
Spain	HU Clínico de Valladolid	Valladolid
Sweden	Linköping University Hospital	Linköping
Switzerland	Inselspital, University Hospital	Bern
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	The Newcastle Upon Tyne Hospitals Nhs Foundation Trust	Newcastle Upon Tyne
United Kingdom	Queens Medical Centre	Nottingham
United Kingdom	Oxford University Hospitals NHS Foundation Trust	Oxford
United States	Pinnacle Clinical Research	San Antonio	Texas

Sponsors (24)

Lead Sponsor

Collaborator

University of Oxford

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Antaros Medical, Assistance Publique - Hôpitaux de Paris, Boehringer Ingelheim, ICAN Nutrition Education and Research, Intercept Pharmaceuticals, Linkoeping University, Newcastle University, Novartis, Perspectum, Pfizer, Pinnacle Clinical Research, PLLC, Resoundant Inc, Takeda, University Medical Center Mainz, University of Angers, University of Bern, University of Cambridge, University of Helsinki, University of Nottingham, University of Palermo, University of Seville, University of Turin, Italy

Countries where clinical trial is conducted

United States,  Finland,  France,  Germany,  Greece,  Italy,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic accuracy of imaging biomarkers for severity of liver fibrosis on histology as reference standard	sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve	baseline
Secondary	Diagnostic accuracy of imaging biomarkers for diagnosis of NASH on histology as reference standard	sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve	baseline
Secondary	Diagnostic accuracy of imaging biomarkers for histologically assessed fat and iron deposition as reference standard	sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve	baseline
Secondary	To study the natural history of NAFLD and how this may impact prognosis	Longitudinal correlation of change (d) in MR and US elastography biomarker values with clinical phenotype data*; Survival analysis for the change (d) in biomarker values	evaluation of biomarkers at baseline and after 2 years
Secondary	To evaluate reproducibility and observer dependent variability in reporting of liver imaging biomarkers	Statistical correlation of MR and US elastography data obtained from the same patients acquired or analysed on two time points	evaluation of biomarkers within 30 days
Secondary	To identify physiological factors that confound the performance of imaging biomarkers for the assessment of fibrosis	Statistical correlation of MR scans and US elastography imaging biomarkers with liver histology parameters (steatosis, iron deposition, inflammation) and other clinical data (demographics, lab results, patient characteristics)	baseline