NAFLDNCT05479721
LITMUS Imaging Study
An observational study of NAFLD and NASH, run by University of Oxford at 18 sites in 10 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- NAFLD, NASH, NASH - Nonalcoholic Steatohepatitis
- How many people
- 450 participants
- Where
- 18 sitesin 10 countries
- Study dates
- 4 Sep 2019to 31 Oct 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- Recruited to the European NAFLD Registry
- 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.
- Participant is willing and able to give informed consent for participation in the study.
Who cannot join
- 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.
- 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)
- 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)
Trial locations and contacts
18 sites in 10 countries.
18 sites in 10 countries
United Kingdom4 sites
Addenbrookes Hospital
Cambridge
The Newcastle Upon Tyne Hospitals Nhs Foundation Trust
Newcastle upon Tyne, NE7 7DN
Queens Medical Centre
Nottingham
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU
Spain3 sites
Vall d'Hebron University Hospital
Barcelona
Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital
Seville
HU Clínico de Valladolid
Valladolid
France2 sites
Le Centre de Recherche Clinique (CRC) du CHU d'Angers
Angers
Institut ICAN - Institute of Cardiometabolism And Nutrition Hôpital de la Pitié Salpêtrière
Paris
Germany2 sites
UNIVERSITÄTSMEDIZIN der Johannes Gutenberg Universität Mainz
Mainz
Universitätsklinikums Würzburg
Würzburg
Italy2 sites
Università di Palermo
Palermo
Department of Medical Sciences University of Torino
Torino
United States1 site
Pinnacle Clinical Research
San Antonio, Texas, 78201
About this 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
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.
Read the 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).
- 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
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Cirrhosis, Fatty Liver, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| LITMUS Imaging Study Group | Patients within the European NAFLD Registry who have also consented to participate in the LITMUS Imaging study |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline
Secondary outcomes (5)
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
Measured: baseline
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
Measured: baseline
To study the natural history of NAFLD and how this may impact prognosis
- Longitudinal correlation of change (δ) in MR and US elastography biomarker values with clinical phenotype data*
- Survival analysis for the change (δ) in biomarker values
Measured: evaluation of biomarkers at baseline and after 2 years
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
Measured: evaluation of biomarkers within 30 days
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)
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2022
- Study start4 Sep 2019
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NAFLDStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Newcastle University, University of Nottingham, University of Cambridge, University of Seville, Pinnacle Clinical Research, PLLC, ICAN Nutrition Education and Research, Assistance Publique - Hôpitaux de Paris, Angers University, University of Palermo, University of Turin, Italy, University Medical Center Mainz, University of Helsinki, University of Bern, Linkoeping University, Perspectum, Antaros Medical, Resoundant Inc, Pfizer, Novartis, Takeda, Intercept Pharmaceuticals, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Michael Pavlides, MBBS, DPhil, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05479721
- Sponsor's protocol ID
- IRAS ID 250344
- Other IDs
- 18/LO/1953
- Status last verified
- Apr 2025
- First submitted
- 26 Jul 2022
- Last updated
- 16 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37802221
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05479721
- Acronym / sponsor ID
- IRAS ID 250344
- Keywords
- Liver MultisScan, Magnetic Resonance Elastography, Magnetiic Resonance Imaging, deMILI, diffusion weighted imaging, proton density fat fraction, PDFF, iron corrected T1
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Newcastle University, University of Nottingham, University of Cambridge, University of Seville, Pinnacle Clinical Research, PLLC, ICAN Nutrition Education and Research, Assistance Publique - Hôpitaux de Paris, Angers University, University of Palermo, University of Turin, Italy, University Medical Center Mainz, University of Helsinki, University of Bern, Linkoeping University, Perspectum, Antaros Medical, Resoundant Inc, Pfizer, Novartis, Takeda, Intercept Pharmaceuticals, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Boehringer Ingelheim
- Study start
- 4 Sep 2019 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Oct 2025 (estimated)
- First posted
- 29 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LITMUS Imaging Study Group | – | –Patients within the European NAFLD Registry who have also consented to participate in the LITMUS Imaging study |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (3 listed)
- Recruited to the European NAFLD Registry
- 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.
- Participant is willing and able to give informed consent for participation in the study.
Key exclusion criteria (3 listed)
- 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.
- 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)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic accuracy of imaging biomarkers for severity of liver fibrosis on histology as reference standard
Time frame: baseline
sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve
5 secondary outcomes
Diagnostic accuracy of imaging biomarkers for diagnosis of NASH on histology as reference standard
Time frame: baseline
Diagnostic accuracy of imaging biomarkers for histologically assessed fat and iron deposition as reference standard
Time frame: baseline
To study the natural history of NAFLD and how this may impact prognosis
Time frame: evaluation of biomarkers at baseline and after 2 years
To evaluate reproducibility and observer dependent variability in reporting of liver imaging biomarkers
Time frame: evaluation of biomarkers within 30 days
To identify physiological factors that confound the performance of imaging biomarkers for the assessment of fibrosis
Time frame: baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2025.
- Background: PubMed 37802221Pavlides 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Pavlides, MBBS, DPhil principal investigator
University of Oxford
18 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of NAFLD and NASH, run by University of Oxford at 18 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United Kingdom, Spain, France, Germany, Italy and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy of imaging biomarkers for severity of liver fibrosis on histology as reference standard (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05479721, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2025.