Gut Microbiome and Metabolome in Patients With Gallstone Disease After Surgical and Endoscopic Interventions

Bile Duct Diseases Clinical Trial

Official title:

A Prospective Cohort Study of Translational Changes in Gut Microbiome and Metabolome in Patients With Gallstone Disease After Surgical and Endoscopic Interventions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05689255
• Other study ID #: GMM1
• Status: Recruiting
• Start date: December 23, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2023
• Source: Changi General Hospital
• Contact: Seok Hwee Koo
• Phone: +6568504929
• Email: seok_hwee_koo[@]cgh.com.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this longitudinal observational cohort study is to examine the changes in the composition and diversity of gut microbiome and systemic metabolome in patients with symptomatic gallbladder stones with or without concomitant common bile duct (CBD) stones who will be undergoing cholecystectomy with or without prior endoscopic sphincterotomy (ERCP-ES) and CBD stones extraction. The main questions it aims to answer are whether there are:

• differences in gut microbiome diversity and composition before and after cholecystectomy

• differences in systemic metabolome before and after cholecystectomy

• gut microbiome and systemic metabolome changes after cholecystectomy

Participants will be asked to provide stool, urine, plasma and saliva samples prior to and 1-6 months after cholecystectomy. For patients with concomitant CBD stones who undergo ERCP-ES before cholecystectomy, bile specimens will be collected from the bile duct during ERCP-ES as well as the gallbladder and/or during cholecystectomy.

Description:

This is a longitudinal observational cohort study that will examine the changes in the composition and diversity of gut microbiome and systemic metabolome in patients with symptomatic gallbladder stones with or without concomitant CBD stones who will be undergoing cholecystectomy with or without prior ERCP-ES and CBD stones extraction. This is a single centre study involving the Department of Gastroenterology and Hepatology and the Department of General Surgery at Changi General Hospital, SingHealth, Singapore.

Patients with symptomatic gallstones with or without CBD stones being planned for cholecystectomy will be recruited from both inpatient and outpatient settings. Upon enrolment, baseline clinical characteristics will be recorded, and biospecimens (stool, urine, plasma and saliva) will be collected prior to cholecystectomy for subsequent gut microbiome and systemic metabolome analysis. For patients with concomitant CBD stones who undergo ERCP-ES before cholecystectomy, bile specimens will be collected from the bile duct during ERCP-ES as well as the gallbladder during cholecystectomy, for subsequent bile microbiome analysis. After cholecystectomy, during the scheduled clinic review at 1 to 6 months post-surgery, patients will be reviewed for symptoms of post cholecystectomy syndrome (PCS) or post cholecystectomy diarrhoea (PCD), and biospecimens (stool, urine, plasma and saliva) will again be collected for subsequent gut microbiome and systemic metabolome analysis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 65
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 80 Years

Eligibility

Inclusion Criteria:

• Aged 21 years to 80 years

• Diagnosis of symptomatic gallstone disease without or with concomitant bile duct stones based on prior diagnostic radiological imaging such as transabdominal ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) or endoscopic ultrasound (EUS).

• Will be scheduled for cholecystectomy with or without concomitant ERCP-ES for treatment.

• Patient is willing to provide informed consent before enrolment in the study.

Exclusion Criteria:

• Subjects undergoing ERCP-ES with no intention for future cholecystectomy

• Use of antibiotics or probiotics within 1 month (exception: use of antibiotics within 48 hours of cholecystectomy or ERCP, as metagenomics will be able to sequence both dead and live bacteria, and marked compositional change is not expected within this time frame)

• Presence of malignancy diagnosed within the last 1 year

• Previous gastrectomy, appendicectomy, small bowel or large bowel surgery

• Inflammatory bowel disease

• Active gastrointestinal tract infections

Related Conditions & MeSH terms

• Bile Duct Diseases
• Cholecystolithiasis
• Cholelithiasis
• Gallstone Disease
• Gallstones

Locations

Country	Name	City	State
Singapore	Changi General Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Changi General Hospital

Country where clinical trial is conducted

Singapore, 

References & Publications (4)

Chen Y, Wu S, Tian Y. Cholecystectomy as a risk factor of metabolic syndrome: from epidemiologic clues to biochemical mechanisms. Lab Invest. 2018 Jan;98(1):7-14. doi: 10.1038/labinvest.2017.95. Epub 2017 Sep 11. — View Citation

Di Ciaula A, Garruti G, Wang DQ, Portincasa P. Cholecystectomy and risk of metabolic syndrome. Eur J Intern Med. 2018 Jul;53:3-11. doi: 10.1016/j.ejim.2018.04.019. Epub 2018 Apr 26. — View Citation

Latenstein CSS, Alferink LJM, Darwish Murad S, Drenth JPH, van Laarhoven CJHM, de Reuver PR. The Association Between Cholecystectomy, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease: A Population-Based Study. Clin Transl Gastroenterol. 2020 Apr;11(4):e00170. doi: 10.14309/ctg.0000000000000170. — View Citation

Reid FD, Mercer PM, harrison M, Bates T. Cholecystectomy as a risk factor for colorectal cancer: a meta-analysis. Scand J Gastroenterol. 1996 Feb;31(2):160-9. doi: 10.3109/00365529609031981. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut microbiome profile using metagenomic shotgun sequencing	Fresh stool samples will be collected for microbial DNA extraction prior to and 1-6 months after cholecystectomy. Microbial DNA will be extracted from the stool samples and used for metagenomic shotgun sequencing.	1-6 months
Primary	Systemic metabolome profile using targeted and untargeted metabolomic analysis	Urine, plasma and saliva samples will be collected for metabolomic profiling prior to and 1-6 months after cholecystectomy.	1-6 months
Secondary	Bile microbiome profile using metagenomic shotgun sequencing	Bile samples will be collected for microbial DNA extraction ERCP and endoscopic sphincterotomy	1-6 months