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

Cirrhosis Clinical Trial

— FRAMES  

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04925362
• Other study ID #: APHP190417
• Secondary ID: 2019-A01308-49
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2021
• Est. completion date: June 2036

Study information

• Verified date: May 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Vlad RATZIU
• Phone: 0142161001
• Email: vlad.ratziu[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 900
• Est. completion date: June 2036
• Est. primary completion date: June 2036
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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)
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Ballooning grade		At baseline
Secondary	Lobular inflammation	Composite scores of Lobular inflammation (Ballooning and Inflammation)	At baseline
Secondary	Steatohepatitis	Presence or Absence	At baseline
Secondary	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
Secondary	Obesity	Obesity defined by either : Increased waist circumference by ethnically adjusted criteria or; BMI =25	Change from baseline to 10 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Fasting insulin		Change from baseline to 10 years
Secondary	Insulin sensitivity	HOMA - %s	Change from baseline to 10 years