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The European NAFLD Registry

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ClinicalTrials.gov Identifier: NCT04442334
Recruitment Status : Recruiting
First Posted : June 22, 2020
Last Update Posted : May 19, 2022
Sponsor:
Collaborators:
Newcastle-upon-Tyne Hospitals NHS Trust
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Institute of Cardiometabolism and Nutrition, France
University of Cambridge
Örebro University, Sweden
University of Bern
University of Oxford
University of Turin, Italy
University of Angers
University Hospital, Antwerp
Linkoeping University
University of Helsinki
UMC Utrecht
National and Kapodistrian University of Athens
University of Lisbon
University of Milan
University of Palermo
Catholic University of the Sacred Heart
Wuerzburg University Hospital
RWTH Aachen University
University of Nottingham
Medical University of Vienna
University of Birmingham
University of Florence
Assistance Publique - Hôpitaux de Paris
University Medical Center Mainz
Information provided by (Responsible Party):
Newcastle University

Brief 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.

Condition or disease
NAFLD NASH NASH - Nonalcoholic Steatohepatitis Fibrosis, Liver Steatosis of Liver Hepatocellular Carcinoma Cardiovascular Diseases Type 2 Diabetes Dyslipidaemia Hypertension Obesity Other Associated Comorbidities

Detailed 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.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 10000 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 10 Years
Official Title: The European NAFLD Registry
Actual Study Start Date : May 1, 2015
Estimated Primary Completion Date : December 31, 2030
Estimated Study Completion Date : December 31, 2030

Resource links provided by the National Library of Medicine


Group/Cohort
The LITMUS Study Cohort
Prospectively recruited NAFLD patients, recruited according to The European NAFLD Registry study protocol.
The LITMUS Metacohort
Collated data and biological samples on patients with histologically characterised NAFLD prospectively recruited at contributing academic centres across Europe.
EFPIA Clinical Trial Cohort
Collated data and biological samples on patients with histologically characterised NAFLD that have participated in phase 2 and phase 3 trials of IMPs for NAFLD.



Primary Outcome Measures :
  1. Detailed Characterisation of the NAFLD Patient Phenotype [ Time Frame: 1 day ]
    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.


Secondary Outcome Measures :
  1. Disease Natural History [ Time Frame: Through to study completion, an average of 5 years ]

    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.


  2. Lifestyle factors: Dietary Habits [ Time Frame: Through study completion, an average of 5 years ]
    Cross-sectional and longitudinal study of dietary habits in patients with NAFLD using: Mediterranean Diet Score.

  3. Lifestyle factors: Activity/Exercise [ Time Frame: Through study completion, an average of 5 years ]
    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).

  4. Health Related Quality of Life: CLDQ [ Time Frame: Through study completion, an average of 5 years ]
    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).

  5. Health Related Quality of Life: EQ5D5L [ Time Frame: Through study completion, an average of 5 years ]
    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

  6. Health Related Quality of Life: NASH-CHECK [ Time Frame: Through study completion, an average of 5 years ]
    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.


Biospecimen Retention:   Samples With DNA
Blood (serum, plasma, whole blood, DNA, RNA), Liver tissue, Urine, stool, DNA, RNA


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adult patients with a pre-existing liver biopsy providing histological evidence of NAFLD or, patients undergoing liver biopsy for suspected NAFLD with biochemical and/or radiological findings consistent with NAFLD, or patients with radiological evidence of cirrhosis (in absence of an alternative aetiology) plus presence of ≥2 features indicative of the 'metabolic syndrome'.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04442334


Contacts
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Contact: Quentin M Anstee, MBBS, PhD +44(0)191 20 87012 quentin.anstee@ncl.ac.uk
Contact: Kristy L Wonders, BA, MLitt +44(0)191 2083959 kristy.wonders@ncl.ac.uk

Locations
Show Show 37 study locations
Sponsors and Collaborators
Newcastle University
Newcastle-upon-Tyne Hospitals NHS Trust
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Institute of Cardiometabolism and Nutrition, France
University of Cambridge
Örebro University, Sweden
University of Bern
University of Oxford
University of Turin, Italy
University of Angers
University Hospital, Antwerp
Linkoeping University
University of Helsinki
UMC Utrecht
National and Kapodistrian University of Athens
University of Lisbon
University of Milan
University of Palermo
Catholic University of the Sacred Heart
Wuerzburg University Hospital
RWTH Aachen University
University of Nottingham
Medical University of Vienna
University of Birmingham
University of Florence
Assistance Publique - Hôpitaux de Paris
University Medical Center Mainz
Investigators
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Principal Investigator: Quentin M Anstee, MBBS, PhD Newcastle University
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Newcastle University
ClinicalTrials.gov Identifier: NCT04442334    
Other Study ID Numbers: 08759
634413 ( Other Grant/Funding Number: EU H2020 )
777377 ( Other Grant/Funding Number: EU H2020 IMI2 )
First Posted: June 22, 2020    Key Record Dates
Last Update Posted: May 19, 2022
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Newcastle University:
NAFLD
NASH
Steatohepatitis
Liver
Cirrhosis
Non-alcoholic fatty liver disease
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Cirrhosis
Cardiovascular Diseases
Dyslipidemias
Fibrosis
Pathologic Processes
Digestive System Diseases
Liver Diseases
Lipid Metabolism Disorders
Metabolic Diseases