The aim of this study is to explore the biological and microbial alterations after cholecystectomy that contribute to the pathophysiology of metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD).
ID
Source
Brief title
Condition
- Gallbladder disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is changes in serum Fibroblast Growth Factor 19
(FGF-19) concentration in response to a standardized fat load.
Secondary outcome
Secondary outcome measures are: 1) changes in hepatic steatosis (MASLD)
(assessed by ultrasound imaging of the liver); 2) changes in incidence of
metabolic syndrome (waist circumference, BMI, blood pressure, glucose
intolerance/insulin resistance (glucose tolerance test)); 3) changes in
post-prandial bile-salt excursion; 4) changes in incretin response (GLP-1,
GIP); 5) changes in lipid spectrum (TC, triglyceride, LDL, HDL, VLDL); 6)
changes in glucose tolerance; 7) changes in faecal microbial composition.
Background summary
Cholecystectomy is currently recommended as the standard treatment for
uncomplicated symptomatic gallstone disease. Although it is generally thought
that long-term consequences are uncommon, studies suggest an increased risk of
developing metabolic syndrome and metabolic dysfunction- associated steatotic
liver disease (MASLD). Changes in the dynamics of enterohepatic circulation of
bioactive bile salts, and the reduction in metabolic activity of the
gallbladder are biologically plausible and may underly the pathophysiological
mechanism following cholecystectomy.
Study objective
The aim of this study is to explore the biological and microbial alterations
after cholecystectomy that contribute to the pathophysiology of metabolic
syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD).
Study design
Prospective case control study.
The study will comprise two treatment arms both containing 20 patients (total
of 40 patients).
1. Patients with symptomatic gallstone disease who undergo elective
cholecystectomy.
2. Patients with (a)symptomatic gallstone disease that are treated
conservatively.
Intervention
At four pre-specified intervals (baseline, after 3 months, 1 year, and 2
years), all enrolled patients will be administered a standardized fat load
(whipped cream), followed by systematic collection of postprandial blood
samples. Furthermore, patients will complete lifestyle questionnaires, undergo
basic physical examinations (including measurements of weight, height, and
waist circumference), a computer assisted ultrasound (CAUS) imaging of the
liver will be conducted to determine liver steatosis, and faecal samples will
be collected.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit, and group relatedness: In this study, participants will be required to
make four visits to the Radboud University Medical Centre during follow-up,
consuming approximately half a day each time. To alleviate the time burden for
patients, we have opted to assess liver steatosis solely through ultrasound
imaging. Traditionally, diagnosing MASLD involves a combination of ultrasound
and liver biopsy. However, the computer-assisted ultrasound employed in this
study allows for determining liver cell fat content without the necessity of a
biopsy. This substantially lessens the burden for the patient. Participation in
this study poses no risks or side effects, as we do not intervene with the
standard provided treatment.
Geert Grooteplein zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
• Patients referred to a surgeon with abdominal complaints and ultrasound
proven gallstones or sludge (proven before or after referral) subjected to a
laparoscopic cholecystectomy or conservative treatment
• Availability of informed consent.
• Age 30-60 years
Exclusion criteria
• Patients with pre-operative signs of complicated gallstone disease
(cholecystitis, choledocholithiasis, cholangitis, pancreatitis),
• Signs of cholestasis requiring intervention (e.g. Endoscopisch Retrograde
Cholangio- en Pancreaticografie)
• ASA score III (patient with severe systemic disease (e.g. morbid obesity,
renal failure) or IV (patient with severe systemic disease that is a constant
threat to life)
• Malignancy (excluding skin malignancies: basal cell carcinoma and
non-metastatic squamous cell carcinoma)
• History after bariatric surgery or expected bariatric procedure within 2
years.
• History of inflammatory bowel disease.
• History of alcohol abuse (man >3 and women >2 glasses per day)
• Liver disease (i.e. (autoimmune hepatitis)
• Use steatogenic medication (i.e., methotrexate, tamoxifen, amiodarone, and
systemic corticosteroids)
• Use of DPP4-inhibitors
• Diabetes mellitus
• Use of antibiotics in the previous 3 months
• Gastro-intestinal surgery in the previous 3 months
• Stoma (small bowel or colon)
• Patients that are lactose intolerant / allergic to dairy
• Known anaemia < 6 mmol/l
• Expected short life span of less than 12 months
- Body Mass Index (BMI) >30
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL87032.091.24 |