The European NAFLD Registry

Obesity Clinical Trial

Official title:

The European NAFLD Registry

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04442334
• Other study ID #: 08759
• Secondary ID: 634413777377
• Status: Recruiting
• Start date: May 1, 2015
• Est. completion date: December 31, 2030

Study information

• Verified date: January 2023
• Source: Newcastle University
• Contact: Quentin M Anstee, MBBS, PhD
• Phone: +44(0)191 20 87012
• Email: quentin.anstee[@]ncl.ac.uk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The European NAFLD Registry is a prospectively recruited, observational study supporting the study of the clinical phenotype, natural history, disease outcomes and pathophysiology of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. The ultimate goals are to better understand the drivers of interpatient variation in disease pathophysiology and severity and to utilise this information to develop and validate biomarkers that, singly or in combination, enable detection and monitoring of disease progression and/or from NAFL through NASH to fibrosis and cirrhosis.

Description:

The European NAFLD Registry is a major international collaboration between clinical academics at leading universities across Europe, initially established with funding from the European Association for the Study of the Liver and through the EU FP7, H2020 and IMI2 schemes to the projects FLIP (Fatty Liver Inhibition of Progression), EPoS (Elucidating Pathways of Steatohepatitis) and LITMUS (Liver Investigation: Testing marker Utility in Steatohepatitis). The Registry is a non-interventional, observational study collecting cross-sectional and longitudinal clinical data (including clinical biochemistry/haematology, liver histology, comorbidities, prescribed medication and imaging data) and linked biological samples (Blood [Serum, Plasma], Liver Tissue, Urine, Stool) from prospectively recruited patients with NAFLD. Its purpose is to support clinical and translational research into disease pathophysiology (through development of comprehensive genetic, epigenetic, transcriptomic, metabolomic, proteomic and metagenomic datasets) and biomarker development/validation. It supports collaborative discovery science and serves as the basis for a broad international project to discover and validate biomarkers for NAFLD and associated medical conditions (LITMUS). Out-with the current study, following separate ethical approval and after separate consent, patients who have agreed to join the European NAFLD Registry may also agree to participate in a number of nested sub-studies with bi-directional sharing of data. These include the LITMUS Imaging Study, which will acquire additional imaging data across a range of modalities including, amongst others, MR-PDFF and MR-Elastography. The Registry population comprises adult patients (aged ≥18 years) with risk factors for non-alcoholic fatty liver disease (NAFLD) prospectively recruited primarily in hepatology and diabetology clinics and/or bariatric surgery units at centres across Europe. After receiving informed consent, patients will be assigned a unique study identifier (which will be used to identify all data and samples collected) which will allow all information to be recorded in a link-anonymised form.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10000
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Age =18 years.

2. Clinically suspected NAFLD based on any of:

1. Patient with historical liver biopsy providing histological evidence of NAFLD or,

2. Patient undergoing liver biopsy for suspected NAFLD with biochemical and/or radiological findings consistent with NAFLD or,

3. Patient with radiological evidence of cirrhosis (in absence of an alternative

aetiology) plus presence of =2 features indicative of the 'metabolic syndrome':

• Increased waist circumference by ethnically adjusted criteria (e.g. Europid male/female =94cm/80cm) or overweight/obese (BMI =25);
• Raised fasting glucose =100 mg/dL [5.6 mmol/L], HbA1c =48mmol/mol (6.5%) or previously diagnosed insulin resistance/type 2 diabetes mellitus (or on treatment);
• Dyslipidaemia (fasting TG level =150 mg/dL [1.7 mmol/L]; or fasting HDL <40 mg/dL [1.03 mmol/L] in males and <50 mg/dL [1.29 mmol/L] in females; or on treatment);
• Hypertension (systolic BP =130 or diastolic BP =85 mmHg, or on treatment).

3. Average alcohol consumption less than 21/14 units/week (males/females) in preceding 6 months and no history of sustained excessive consumption of alcohol in past 5 years. Exclusion Criteria

1. Refusal or inability (lack of capacity) to give informed consent.

2. Average alcohol ingestion greater than approximately 21/14 units/week (males/females) in preceding 6 months or history of sustained excessive consumption of alcohol in past 5 years.

3. History or presence of Type 1 diabetes mellitus.

4. Presence of any other form of chronic liver disease except NAFLD.

5. Recent (within 12 months) or concomitant use of agents known to cause hepatic steatosis (long-term systemic corticosteroids [>10 days], amiodarone, methotrexate, tamoxifen, tetracycline, high dose oestrogens, valproic acid).

6. Any contra-indication to liver biopsy.

7. Recent (within 3 months) change in dose/regimen or introduction of Vitamin E (at a dose =400 IU/day), betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin or pentoxifylline.

8. Non-English speaking/unable to access an interpreter. Due to the nature of the study, English language or access to a relevant interpreter is a necessary criterion to ensure lifestyle (diet and exercise) and symptom data are collated.

9. Patients not meeting inclusion criteria or judged by the investigator to be unsuitable for inclusion in the study.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Dyslipidaemia
• Dyslipidemias
• Fatty Liver
• Fibrosis, Liver
• Hepatocellular Carcinoma
• Hypertension
• Liver Cirrhosis
• NAFLD
• NASH
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease
• Obesity
• Other Associated Comorbidities
• Steatosis of Liver
• Type 2 Diabetes

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Antwerp
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	UNIVERSITÄTSKLINIKUM der RWTH Aachen	Aachen
Germany	Charité University Hospital Berlin	Berlin
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	UNIVERSITÄTSMEDIZIN der Johannes Gutenberg Universität Mainz	Mainz
Germany	Universitätsklinikums Würzburg	Würzburg
Greece	Laiko General Hospital of Athens	Athens
Italy	Polytechnic University of Marche	Ancona
Italy	Università degli Studi Milano	Milan
Italy	Università di Palermo	Palermo
Italy	Università Cattolica del Sacro Cuore	Rome
Italy	Department of Medical Sciences University of Torino	Turin
Netherlands	Amsterdam UMC	Amsterdam
Portugal	Hospital de Santa Maria	Lisboa
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Biodonostia Health Research Institute	Donostia
Spain	Puerta de Hierro University Hospital	Majadahonda
Spain	Marqués de Valdecilla University Hospital	Santander
Spain	Institute of Biomedicine of Sevilla (IBiS), Virgen del Rocío University Hospital	Sevilla
Spain	HU Clínico de Valladolid	Valladolid
Sweden	Karolinska Universitetssjukhuset	Huddinge
Sweden	Linköping University Hospital	Linköping
Switzerland	Inselspital, University Hospital	Bern
United Kingdom	University Hospitals Birmingham Nhs Foundation Trust	Birmingham
United Kingdom	Addenbrooke'S Hospital	Cambridge
United Kingdom	Queen Elizabeth Hospital	Gateshead
United Kingdom	Hull Royal Infirmary	Hull
United Kingdom	Royal London Hospital, Barts Health NHS Trust	London
United Kingdom	St George's University Hospitals	London
United Kingdom	The Newcastle Upon Tyne Hospitals Nhs Foundation Trust	Newcastle-upon Tyne
United Kingdom	Queen'S Medical Centre	Nottingham
United Kingdom	Oxford University Hospitals Nhs Foundation Trust	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Queen Alexandra Hospital	Portsmouth

Sponsors (27)

Lead Sponsor

Collaborator

Newcastle University

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Assistance Publique - Hôpitaux de Paris, Catholic University of the Sacred Heart, Institute of Cardiometabolism and Nutrition, France, Linkoeping University, Medical University of Vienna, National and Kapodistrian University of Athens, Newcastle-upon-Tyne Hospitals NHS Trust, Örebro University, Sweden, RWTH Aachen University, UMC Utrecht, University Hospital, Antwerp, University Medical Center Mainz, University of Angers, University of Bern, University of Birmingham, University of Cambridge, University of Florence, University of Helsinki, University of Lisbon, University of Milan, University of Nottingham, University of Oxford, University of Palermo, University of Turin, Italy, Wuerzburg University Hospital

Countries where clinical trial is conducted

Belgium,  Finland,  France,  Germany,  Greece,  Italy,  Netherlands,  Portugal,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detailed Characterisation of the NAFLD Patient Phenotype	Prospective patient recruitment and collection of cross-sectional clinical data is undertaken (including clinical biochemistry/haematology, liver histology, comorbidities, prescribed medication and imaging data).These data will be used to determine number of participants exhibiting specific features of NAFLD/NASH disease severity at enrolment including: histological grade of disease and fibrosis stage (assessed using the well validated NASH Clinical Research Network "NAFLD Activity Score" [NAS] and the FLIP "Steatosis - Activity - Fibrosis" [SAF] systems), frequency of common metabolic comorbidities (eg type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease), and associated changes in clinical biochemistry/haematology/imaging parameters. Biological samples to support clinical and translational research into disease pathophysiology (e.g. genetic, epigenetic, transcriptomic, metabolomic, proteomic and metagenomic datasets) and biomarker development/validation will be collected.	1 day
Secondary	Disease Natural History	Longitudinal follow-up of patients with NAFLD by annual review to characterise disease natural history and determine number of participants experiencing clinically significant events including the occurrence and timing of incident comorbidities and key target conditions of interest such as: Death (cause of death); Major Adverse Cardiovascular Events (MACE); Hepatic (e.g. diagnosis of cirrhosis, hepatic decompensation, hepatocellular carcinoma, transplantation); Other (diagnosis of extra-hepatic malignancy/emergency hospitalisation); Routine clinical data generated as part of standard care will be collected annually. Clinical parameters assessed for changes indicative of alteration in disease state during follow-up include: clinical biochemistry/haematology, liver histology, comorbidities, prescribed medication and imaging data. Biological samples to support translational research into disease pathophysiology and biomarker development/validation will also be collected.	Through to study completion, an average of 5 years
Secondary	Lifestyle factors: Dietary Habits	Cross-sectional and longitudinal study of dietary habits in patients with NAFLD using: Mediterranean Diet Score.	Through study completion, an average of 5 years
Secondary	Lifestyle factors: Activity/Exercise	Cross-sectional and longitudinal study of lifestyle factors (e.g. activity/sedentary behaviour/exercise levels) in patients with NAFLD using: International Physical Activity Questionnaire (IPAQ).	Through study completion, an average of 5 years
Secondary	Health Related Quality of Life: CLDQ	Cross-sectional and longitudinal collection of standardised data on HRQOL and symptom burden in patients with NAFLD using Patient Reported Outcome Measure (PROM): Chronic Liver Disease Questionnaire for NAFLD NASH (CLDQ NAFLD-NASH).	Through study completion, an average of 5 years
Secondary	Health Related Quality of Life: EQ5D5L	Cross-sectional and longitudinal collection of standardised data on HRQOL and symptom burden in patients with NAFLD using Patient Reported Outcome Measure (PROM): EQ-5D-5L Health	Through study completion, an average of 5 years
Secondary	Health Related Quality of Life: NASH-CHECK	Cross-sectional and longitudinal collection of standardised data on HRQOL and symptom burden in patients with NAFLD using Patient Reported Outcome Measure (PROM): NASH-CHECK.	Through study completion, an average of 5 years