The Franciscus Obesity NASH Study

Not yet recruiting

• Conditions: NAFLD; NASH - Nonalcoholic Steatohepatitis; Obesity, Morbid
• Interventions: Diagnostic Test: NASH screening; Diagnostic Test: Cardiac dysfunction screening; Diagnostic Test: Liver biopsy

• Registration Number: NCT05499949
• Lead Sponsor: Franciscus Gasthuis

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.

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 Timeline

• Status Verified: 2022-08
• Study First Submitted: 2022-08-11
• Study First Submitted QC: 2022-08-11
• Last Update Submitted: 2022-08-11
• Study First Posted: 2022-08-12
• Last Update Posted: 2022-08-12
• Study Start: 2022-09-01
• Primary Completion: 2023-06-01
• Study Completion: 2029-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 300

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
FONS group	Cardiac dysfunction screening	Patients with morbid obesity enrolled for bariatric surgery in the Franciscus Gasthuis, Rotterdam, the Netherland
FONS group	NASH screening	Patients with morbid obesity enrolled for bariatric surgery in the Franciscus Gasthuis, Rotterdam, the Netherland
FONS group	Liver biopsy	Patients with morbid obesity enrolled for bariatric surgery in the Franciscus Gasthuis, Rotterdam, the Netherland

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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.
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
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 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 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

Trial Locations

Locations (1)

Franciscus Gasthuis; 🇳🇱 Rotterdam, Zuid Holland, Netherlands