A Novel Oral Synbiotic Formula in Reducing Advanced Adenoma Recurrence and Colorectal Neoplasia-related Bacterial Gene Markers

A Multicenter, Double Blinded Randomized Controlled Trial of a Novel Oral Synbiotic Formula in Reducing Advanced Adenoma Recurrence and Colorectal Neoplasia-related Bacterial Gene Markers

This multicenter, double blinded randomized controlled trial aims to assess the efficacy of a novel oral synbiotic formula (SMT04) in reducing advanced adenoma recurrence and colorectal neoplasia-related bacterial gene markers after endoscopic resection of colorectal advanced neoplasia.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Neoplasms; Colorectal Cancer; Colorectal Adenoma; Advanced Adenoma
• Intervention / Treatment: Other: SMT04 formula; Other: Active placebo

Detailed Description

Recent evidence has demonstrated the association between altered gut microbiome environment and the progression of colorectal cancer (CRC) from its precancerous lesions. Some pathogenic species of bacteria, including Fusobacterium nucleatum, Escherichia Coli and Bacteroides fragilis, have shown to be significantly enriched in CRC patients. This gut dysbiosis process also brings with its diagnostic potential for recurrent adenomas. Previous study found a panel of bacterial gene markers, including "m3" from Lachnoclostridium, F. nucleatum (Fn), Bacteroides clarus (Bc) and Clostridium hathewayi (Ch) could be used in detecting adenoma recurrence after polypectomy in a retrospective study. In addition, these microbial biomarkers may have prognostic potential and provide an option as therapeutic target.

Probiotics, including the genera Bifidobacterium and Lactobacillus, have shown to be able to inhibit tumorigenesis and progression of CRC in animal studies. Prebiotics are non-digestible dietary ingredients with protective effects against cancer by selectively stimulating the growth and activity of beneficial colonic microbiota. The combination of probiotics and prebiotics, known as synbiotic, may be more efficient in preventing CRC than either one alone.

The investigators' unpublished data showed that the new probiotic formula containing Bifidobacterium strains has a negative correlation with CRC-related bacterial gene markers. Subjects treated with SMT04 showed significantly higher levels of the individual Bifidobacterium species at week 2 to week 5 compared with baseline levels. There was a significant decrease in the bacterial gene markers (Fn, m3 and 4Bac CRC risk score) from week 2 to week 12 compared with baseline levels in the SMT04 group but not in the control group. The synbiotic formula (SMT04) is the combination of probiotic formula and several heat-resistant prebiotics. It remains unclear that whether this synbiotic formula can produce a sustained effect in reduction of advanced adenoma recurrence and colorectal neoplasia related bacterial gene markers in long-term.

• Study Type: Interventional
• Enrollment (Estimated): 649
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louis Lau; Phone Number: 35052211; Email: louishslau@cuhk.edu.lhk

Study Locations

• China
  • Inner Mongolia Autonomous Region
    • Hohhot, Inner Mongolia Autonomous Region, China
      • Not yet recruiting
      • Inner Mongolia People's Hospital
      • Contact: Guijun Prof. Zhao, MD; Phone Number: 0471-3283258; Email: cnzhaoguijun@163.com
      • Principal Investigator: Guijun Prof. Zhao, MD
• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital
    • Contact: Louis Lau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects who have advanced colorectal neoplasia* removed and confirmed by histopathology;
• They have received high quality colonoscopies before or during endoscopic resection (defined as a full colonoscopy with successful caecal intubation, and a Boston Bowel Preparation Scale ≧2 in each colonic segment) with no residual colorectal neoplasia;
• Aged 18-90 years old;

• Written informed consent obtained

  • An advanced colorectal neoplasia is defined as an advanced adenoma, sessile serrated lesion or non-invasive colorectal cancer (stage Tis or T1a). Advanced adenoma is defined as an adenoma larger than 10mm, and/or with villous component ≥20%, and/or harboring high grade dysplasia.

Exclusion Criteria:

• Known residual colorectal neoplasia not removed (except hyperplastic polyps);
• Contraindications to endoscopic resection due to deep submucosal invasion (stage T1b or above);
• Prior surgical resection of colon;
• Personal history of hereditary polyposis syndrome or inflammatory bowel disease;
• Known pregnancy or lactation;
• Immunocompromised status (e.g. on immunosuppressants (except 5-aminosalicylic acid or short term use of corticosteroids <4 weeks), on chemotherapy, bone marrow or solid organ transplant, human immunodeficiency virus, congenital immune deficiency);
• Advanced comorbid conditions (defined as American Society of Anesthesiologists grade 4 or above);
• Refusal to undergo surveillance colonoscopy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Receive SMT04 formula	Other: SMT04 formula; The SMT04 formula is a synbiotic containing probiotics and prebiotics
Placebo Comparator: Placebo arm; Receive active placebo	Other: Active placebo; The active placebo is 2 mg Vitamin C with an inert substance made of starch filler. The flavor, coloring and appearance are unidentifiable to the study product.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of metachronous recurrent advanced colorectal neoplasia at year 1 (local or at other sites).	The proportion of patients with metachronous recurrent advanced neoplasia at year 1	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of recurrent adenomas at year 1	The number of recurrent colorectal adenoma per patient both in intervention and placebo arm	1 year
Incidence of recurrent colorectal adenomas at year 1	The proportion of patients with metachronous recurrent adenoma at year 1	1 year
Number of recurrent advanced neoplasia at year 1	The number of recurrent colorectal advanced neoplasia per patient both in intervention and placebo arm	1 year
Changes in the levels of bacterial gene markers	The change in the level of four bacterial gene markers and combined risk score tested by qPCR	1 year
Correlation between recurrent advanced colorectal neoplasia and the changes in levels of bacterial gene markers	Correlation of incidence rate of recurrent advanced colorectal neoplasia and the changes in the level of four bacterial gene markers and combined risk score tested by qPCR	1 year
Correlation between recurrent adenoma and the changes in levels of bacterial gene markers	Correlation of incidence rate of recurrent adenoma and the changes in the level of four bacterial gene markers and combined risk score tested by qPCR	1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Collaborators: Inner Mongolia People's Hospital
• Investigators: Principal Investigator: Louis Lau, Prince of Wales Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Estimated): December 15, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 21, 2022
• First Posted (Actual): October 25, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Bacterial marker; Adenoma recurrence
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Recurrence; Colorectal Neoplasms; Adenoma
• Other Study ID Numbers: 2022.360

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No