Clinical trial NCT05499949: The Franciscus Obesity NASH Study
Official title: The Franciscus Obesity NASH Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: NAFLD
NASH - Nonalcoholic Steatohepatitis
Obesity, Morbid
Keywords: Transient elastography
Bariatric surgery
Lead sponsor: Franciscus Gasthuis
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Erasmus Medical Center
name: Leiden University Medical Center
First posted: 2022-08-12
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants with morbid obesity enrolled for bariatric surgery at the Franciscus Gasthuis, Rotterdam, the Netherlands.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from baseline in liver steatosis and fibrosis 5 years after bariatric surgery
timeFrame: baseline (enrolment) and 5 years after bariatric surgery
Secondary outcomes:
measure: Change from baseline in liver steatosis and fibrosis after lifestyle intervention
timeFrame: baseline (enrolment) and 3 months later
measure: Change from baseline in liver steatosis and fibrosis 1 year after bariatric surgery
timeFrame: baseline (enrolment) and 1 year after bariatric surgery
measure: Change from baseline in liver steatosis and fibrosis 3 years after bariatric surgery
timeFrame: baseline (enrolment) and 3 years after bariatric surgery
measure: Change from baseline in liver steatosis and fibrosis according to the type of bariatric surgery
timeFrame: baseline and 1 and 3 years after bariatric surgery
measure: Change from baseline in liver steatosis and fibrosis according to the genetic profile
timeFrame: baseline and 1 year after surgery
measure: Change from baseline in liver fibrosis according to gender and ethnicities
timeFrame: baseline and 1, 3 and 5 years after bariatric surgery
measure: Change from baseline in liver steatosis and fibrosis according to the gut microbiota
timeFrame: baseline and 1 year after bariatric surgery
measure: Association between NAFLD/NASH and vascular dysfunction
timeFrame: baseline
measure: Association between NAFLD/NASH and cardiac dysfunction
timeFrame: baseline and 1 year after bariatric surgery
measure: Association between change in NAFLD/NASH and change in cardiac dysfunction
timeFrame: baseline and 1 year after bariatric surgery
measure: Correlation between histology and transient elastogrpahy measurement in a population with morbid obesity
timeFrame: during surgery
Other outcomes:
Locations:
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis
state: Zuid Holland
Study officials:
References: