The Franciscus Obesity NASH Study

Obesity, Morbid Clinical Trial

— FONS  

Official title:

The Franciscus Obesity NASH Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05499949
• Other study ID #: FONS
• Status: Not yet recruiting
• Start date: September 1, 2022
• Est. completion date: January 1, 2029

Study information

• Verified date: August 2022
• Source: Franciscus Gasthuis
• Contact: Willy Theel, MSc
• Phone: +31.10461755
• Email: w.theel[@]franciscus.nl
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: January 1, 2029
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

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

1. Participants must fulfil the criteria of the International Federation for the Surgery of Obesity (IFSO) at screening.

2. 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:

1. Participants younger than 18 years or older than 65 years

2. Participants with an established diagnosis of liver pathology like, but not limited to:

1. Hepatitis B

2. Hepatitis C

3. Autoimmune hepatitis

4. Wilson's disease

5. Hemochromatosis

6. Primary biliary cholangitis

7. Primary sclerosing cholangitis

8. Alcoholic liver disease

3. Histologically documented liver cirrhosis (fibrosis stage F4), at screening or in a historical biopsy.

4. Participants with active HIV infection and/or treatment.

5. Participants with diagnosed malignancies with or without active treatment.

6. 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.

7. The participant does not understand Dutch.

Related Conditions & MeSH terms

• Fatty Liver
• NAFLD
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease
• Obesity
• Obesity, Morbid

Intervention

Diagnostic Test:
• NASH screening
Evaluate liver steatosis and elasticity using transient elastography in the FONS group
• Cardiac dysfunction screening
Evaluate cardiac dysfunction in 60 patients from the FONS group with transthoracic echocardiography
• 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.

Locations

Country	Name	City	State
Netherlands	Franciscus Gasthuis	Rotterdam	Zuid Holland

Sponsors (4)

Lead Sponsor	Collaborator
Franciscus Gasthuis	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in liver steatosis and fibrosis 5 years after bariatric surgery	Transient elastography is a non invasive test evaluating liver steatosis and fibrosis	baseline (enrolment) and 5 years after bariatric surgery
Secondary	Change from baseline in liver steatosis and fibrosis after lifestyle intervention	Transient elastography is a non invasive test evaluating liver steatosis and fibrosis	baseline (enrolment) and 3 months later
Secondary	Change from baseline in liver steatosis and fibrosis 1 year after bariatric surgery	Transient elastography is a non invasive test evaluating liver steatosis and fibrosis	baseline (enrolment) and 1 year after bariatric surgery
Secondary	Change from baseline in liver steatosis and fibrosis 3 years after bariatric surgery	Transient elastography is a non invasive test evaluating liver steatosis and fibrosis	baseline (enrolment) and 3 years after bariatric surgery
Secondary	Change from baseline in liver steatosis and fibrosis according to the type of 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.	baseline and 1 and 3 years after bariatric surgery
Secondary	Change from baseline in liver steatosis and fibrosis according to the genetic profile	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.	baseline and 1 year after surgery
Secondary	Change from baseline in liver fibrosis according to gender and ethnicities	To determine if liver elasticity differs between gender or ethnicities before bariatric surgery and the changes 1, 3 and 5 years after bariatric surgery	baseline and 1, 3 and 5 years after bariatric surgery
Secondary	Change from baseline in liver steatosis and fibrosis according to the gut microbiota	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.	baseline and 1 year after bariatric surgery
Secondary	Association between NAFLD/NASH and vascular dysfunction	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	baseline
Secondary	Association between NAFLD/NASH and cardiac dysfunction	To determine if the presence of NAFLD/NASH before bariatric surgery is associated with (subclinical) cardiac dysfunction using transthoracal echocardiography	baseline and 1 year after bariatric surgery
Secondary	Association between change in NAFLD/NASH and change in cardiac dysfunction	To determine if change of liver fibrosis stage is associated to change in cardiac function 1 year after bariatric surgery	baseline and 1 year after bariatric surgery
Secondary	Correlation between histology and transient elastogrpahy measurement in a population with morbid obesity	To establish the correlation between histology (liver biopsy) and transient elastography measurement in a population with morbid obesity	during surgery