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

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

Detailed Description
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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 The investigators' unpublished data showed that the new probiotic formula containing Bifidobacterium strains has a negative correlation with CRC-related bacterial gene markers.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 adenoma recurrence and colorectal neoplasia related bacterial gene markers in long-term.

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

Conditions
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Colorectal Neoplasms, Colorectal Adenoma, Colorectal Cancer

Intervention / Treatment
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* Other: SMT04 formula
* Other: Active placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Subjects have advanced colorectal neoplasia requiring endoscopic resection (endoscopic mucosal resection, endoscopic submucosal dissection, etc.); 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); Aged 18-90 years old; Written informed consent obtained Exclusion Criteria: Known residual colorectal neoplasia not removed (except hyperplastic polyps); Contraindications to endoscopic resection due to deep submucosal invasion; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>Receive SMT04 formula | Other: SMT04 formula<br>* The SMT04 formula is a synbiotic containing probiotics and prebiotics<br>|
| Placebo Comparator: Placebo arm<br>Receive active placebo | Other: Active placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence of metachronous recurrent colorectal adenoma at year 1 (local or at other sites) | The proportion of patients with metachronous recurrent adenoma at year 1 | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of recurrent colorectal advanced adenomas at year 1 | The proportion of patients with metachronous recurrent advanced adenoma at year 1 | 1 year | 
| Number of recurrent adenomas at year 1 | The number of recurrent colorectal adenoma per patient both in intervention and placebo arm | 1 year | 
| Number of recurrent advanced adenomas at year 1 | The number of recurrent colorectal advanced adenoma 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 tested by qPCR | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenoma recurrence, Bacterial marker