FONS: The Franciscus Obesity NASH Study

Sponsor

Franciscus Gasthuis (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05499949

Collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), Erasmus Medical Center (Other), Leiden University Medical Center (Other)

300

Enrollment

Location

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) changes in terms of steatosis and elasticity in patients with morbid obesity 1, 3 and 5 years after bariatric surgery.

In addition, genomics, microbiome and metabolomics analyses will be carried out.

Condition or Disease	Intervention/Treatment	Phase
NAFLD NASH - Nonalcoholic Steatohepatitis Obesity, Morbid	Diagnostic Test: NASH screening Diagnostic Test: Cardiac dysfunction screening Diagnostic Test: Liver biopsy

Detailed Description

After being informed about the study and potential risks, 300 eligible patients will be included.

All participants will undergo lifestyle intervention before bariatric surgery. Extensive cardiometabolic analyses will be carried out. At 5 different moments (twice before and 3 times after bariatric sugery), liver steatosis and elasticity will be evaluate using Fibroscan. For those with an elevated liver fibrosis measurement (TE ≥7.2 kPa with M probe or ≥7.95 kPa with XL probe), a laparoscopic liver biopsy will be performed during surgery. Patients will undergo gastric sleeve resection, Roux-n-Y gastric bypass or gastric minibypass.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Franciscus Obesity NASH Study

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jan 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
FONS group Patients with morbid obesity enrolled for bariatric surgery in the Franciscus Gasthuis, Rotterdam, the Netherland	Diagnostic Test: NASH screening Evaluate liver steatosis and elasticity using transient elastography in the FONS group Diagnostic Test: Cardiac dysfunction screening Evaluate cardiac dysfunction in 60 patients from the FONS group with transthoracic echocardiography Diagnostic Test: Liver biopsy For participants from the FONS group with an elevated liver fibrosis measurement (≥F2) with TE, a laparoscopic liver biopsy will be performed during the bariatric procedure.

Arm

Intervention/Treatment

FONS group

Patients with morbid obesity enrolled for bariatric surgery in the Franciscus Gasthuis, Rotterdam, the Netherland

Diagnostic Test: NASH screening

Evaluate liver steatosis and elasticity using transient elastography in the FONS group

Diagnostic Test: Cardiac dysfunction screening

Evaluate cardiac dysfunction in 60 patients from the FONS group with transthoracic echocardiography

Diagnostic Test: Liver biopsy

For participants from the FONS group with an elevated liver fibrosis measurement (≥F2) with TE, a laparoscopic liver biopsy will be performed during the bariatric procedure.

Outcome Measures

Primary Outcome Measures

Change from baseline in liver steatosis and fibrosis 5 years after bariatric surgery [baseline (enrolment) and 5 years after bariatric surgery]
Transient elastography is a non invasive test evaluating liver steatosis and fibrosis

Secondary Outcome Measures

Change from baseline in liver steatosis and fibrosis after lifestyle intervention [baseline (enrolment) and 3 months later]
Transient elastography is a non invasive test evaluating liver steatosis and fibrosis
Change from baseline in liver steatosis and fibrosis 1 year after bariatric surgery [baseline (enrolment) and 1 year after bariatric surgery]
Transient elastography is a non invasive test evaluating liver steatosis and fibrosis
Change from baseline in liver steatosis and fibrosis 3 years after bariatric surgery [baseline (enrolment) and 3 years after bariatric surgery]
Transient elastography is a non invasive test evaluating liver steatosis and fibrosis
Change from baseline in liver steatosis and fibrosis according to the type of bariatric surgery [baseline and 1 and 3 years after bariatric surgery]
To evaluate if the type of bariatric surgery (gastric sleeve resection, Roux-en-Y Gastric bypass, Gastric minibypass) influences the steatosis and elasticity in patients with morbid obesity, measured 1 and 3 years after bariatric surgery, adjusted for baseline steatosis/elasticity.
Change from baseline in liver steatosis and fibrosis according to the genetic profile [baseline and 1 year after surgery]
To determine if candidate genetic markers (PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13) are associated to changes in NAFLD/NASH severity in patients with morbid obesity one year after bariatric surgery.
Change from baseline in liver fibrosis according to gender and ethnicities [baseline and 1, 3 and 5 years after bariatric surgery]
To determine if liver elasticity differs between gender or ethnicities before bariatric surgery and the changes 1, 3 and 5 years after bariatric surgery
Change from baseline in liver steatosis and fibrosis according to the gut microbiota [baseline and 1 year after bariatric surgery]
To investigate the change in the ratio of Firmicutes/Bacteroides in the distal gut microbiota in patients with morbid obesity with NAFLD/NASH 1 year after bariatric surgery and the effects of these changes on transient elastography measurements.
Association between NAFLD/NASH and vascular dysfunction [baseline]
To determine if the presence of NAFLD/NASH before bariatric surgery is associated with (subclinical) vascular dysfunction using the carotid intima media thickness and pulse wave velocity
Association between NAFLD/NASH and cardiac dysfunction [baseline and 1 year after bariatric surgery]
To determine if the presence of NAFLD/NASH before bariatric surgery is associated with (subclinical) cardiac dysfunction using transthoracal echocardiography
Association between change in NAFLD/NASH and change in cardiac dysfunction [baseline and 1 year after bariatric surgery]
To determine if change of liver fibrosis stage is associated to change in cardiac function 1 year after bariatric surgery
Correlation between histology and transient elastogrpahy measurement in a population with morbid obesity [during surgery]
To establish the correlation between histology (liver biopsy) and transient elastography measurement in a population with morbid obesity

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must fulfil all of the inclusion criteria (unless otherwise specified) for enrolment in the study.

Participants must fulfil the criteria of the International Federation for the Surgery of Obesity (IFSO) at screening.
Participants must be able to understand the nature of the study and written informed consent must be obtained before any study specific interventions are performed.

The cardiac function of a subset group of 30 subjects aged 35 years and older with low transient elastography measurements (≤F1) and no known cardiac disease, hypertension or diabetes mellitus will be compared with a similar number of patients with high transient elastography measurements (≥F3) and no known cardiac disease, hypertension or diabetes mellitus. These patients will be consecutively included.

We will perform a liver biopsy during endoscopic bariatric surgery in the patients with an elevated transient elastography measurement (≥F2; suggesting fibrosis and therefore the presence of NASH) in order to correlate the histological diagnosis to the clinical diagnosis based on elastography. In those patients in whom the diagnosis of NASH is confirmed by histology, more detailed follow up in a separate program at the department of gastroenterology is indicated according to the current guidelines.

Exclusion Criteria:

Patients who meet any of the following criteria at screening (unless otherwise specified) will be excluded from the study:

Participants younger than 18 years or older than 65 years
Participants with an established diagnosis of liver pathology like, but not limited to:
Hepatitis B
Hepatitis C
Autoimmune hepatitis
Wilson's disease
Hemochromatosis
Primary biliary cholangitis
Primary sclerosing cholangitis
Alcoholic liver disease
Histologically documented liver cirrhosis (fibrosis stage F4), at screening or in a historical biopsy.
Participants with active HIV infection and/or treatment.
Participants with diagnosed malignancies with or without active treatment.
Participants with a history or evidence of any other clinically significant condition or planned or expected procedure that in the opinion of the investigator, may compromise the patient's safety or ability to complete the study.
The participant does not understand Dutch.