THE FRENCH NATIONAL NAFLD COHORT (FRench pAtients With MEtabolic Steatosis) (FRAMES)

Identification of Clinical and Biological Factors Determining Disease Severity and Disease Progression in NAFLD: "THE FRENCH NATIONAL NAFLD COHORT" FRAMES (FRench pAtients With MEtabolic Steatosis)

The main objective of this cohort study is to determine genetic, clinical biologic and metabolic factors associated with patient heterogeneity in regards to severity of NAFLD at diagnosis as well as during the clinical course.

• at diagnosis, with the aim to better characterize patients of different severity and improve our understanding of clinical and histological heterogeneity at diagnosis
• during the clinical course to better understand and predict disease progression in terms notably of fibrosis progression and progression to cirrhosis

Study Overview

• Status: Not yet recruiting
• Conditions: Fibrosis; Cirrhosis; NAFLD; NASH - Nonalcoholic Steatohepatitis; NASH
• Intervention / Treatment: Other: Biological specimens; Other: Additional visit

Detailed Description

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and is currently the most common cause of liver disease in many developed countries worldwide.

The aim of the study is to improve the scientific knowledge on markers associated with disease severity and progression in NAFLD.

The study is a multicentre French NAFLD cohort of well-characterized patients with biological samples covering the entire spectrum of NAFLD severity (steatosis, NASH, significant fibrosis, cirrhosis, hepatocellular carcinoma).

• Study Type: Interventional
• Enrollment (Anticipated): 900
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vlad RATZIU; Phone Number: +33 0142161001; Email: vlad.ratziu@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years
2. Patients with a confirmed diagnosis of NAFLD
3. Patients affiliated to French social security
4. Written informed consent signed by the patient

Exclusion Criteria:

1. Refusal or inability (lack of capacity) to give informed consent.
2. Average alcohol ingestion greater than 21/14 units/week (males/females) in the 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-French speaking/unable to access an interpreter.
9. Patients judged by the investigator to be unsuitable for inclusion in the study (e.g. judged by the physician as unlikely to be compliant with the study protocol).
10. Pregnant or breastfeeding women
11. Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Patients; Patients with histologically confirmed NAFLD

Other: Biological specimens; Biological specimens are collected to better characterize patients of different severity and improve our understanding of clinical and histological heterogeneity at diagnosis : added for the research : blood, urine, stools; collected for the research : liver tissue sample, if a liver biopsy is indicated for clinical reasons (standard of care); Other: Additional visit; Visits if possible during standard care, otherwise added by the research (If necessary the annual visit will be added by research for the collection of biological samples)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease severity	The disease severity defined by the fibrosis stage on liver biopsy according to the semi-quantitative histological classification of NASH CRN.	Change of the fibrosis stage from baseline to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ballooning grade		At baseline
Lobular inflammation	Composite scores of Lobular inflammation (Ballooning and Inflammation)	At baseline
Steatohepatitis	Presence or Absence	At baseline
Cirrhosis	Cirrhosis defined by either : stage 4 of histological classification of fibrosis on liver biopsy or; liver stiffness >14 kPa by elastometry	Through study completion, an average of 10 years
Obesity	Obesity defined by either : Increased waist circumference by ethnically adjusted criteria or; BMI ≥25	Change from baseline to 10 years
Type 2 diabetes	Type 2 diabetes defined by 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).	Change from baseline to 10 years
Dyslipidaemia	Dyslipidaemia defined by fasting TG level ≥150 mg/dL [1.7mmol/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);	Change from baseline to 10 years
Cardiovascular disease	Cardiovascular disease defined by arterial hypertension (systolic BP ≥130 or diastolic BP ≥85 mmHg, or on antihypertensive treatment).	Change from baseline to 10 years
Necroinflammation measured by the activities component of the SAF	Necroinflammation measured by the activities component of the SAF classification : ranges 0 to 4 SAF : steatosis, activity, fibrosis	Change from baseline to 10 years
Necroinflammation measured by the NAS score	Necroinflammation measured by the NAS score : ranges from 0 to 8 NAS score : NAFLD Activity Score	Change from baseline to 10 years
Fasting insulin		Change from baseline to 10 years
Insulin sensitivity	HOMA - %s	Change from baseline to 10 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Vlad RATZIU, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): June 1, 2036
• Study Completion (Anticipated): June 1, 2036

Study Registration Dates

• First Submitted: February 24, 2021
• First Submitted That Met QC Criteria: June 7, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Cohort
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: APHP190417; 2019-A01308-49 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No