The Effect of Oral Clostridium Butyricum on the Recurrence After Colonoscopic Resection of Colorectal Adenoma

Official title

The Effect of Oral Clostridium Butyricum on the Recurrence After Colonoscopic Resection of Colorectal Adenoma - A Multicenter, Double-blinded, Differential Design, Randomized, Placebo-controlled Study

Overview

The prevention of recurrence after colorectal adenoma resection remains an urgent medical issue to be addressed. Previous studies have mainly focused on nonsteroidal anti-inflammatory drugs, calcium supplements, and vitamins. The gut microbiota and its metabolic products are believed to play a potential role in the development and progression of colorectal adenomas. Clostridium butyricum, a butyrate-producing probiotic, has not yet been studied for its potential in preventing the recurrence of colorectal adenomas following resection. Therefore, this study, designed as a multicenter, double-blind, placebo-controlled randomized controlled trial, aims to explore evidence-based data on the role of Clostridium butyricum in preventing colorectal adenoma recurrence.

Detailed description

Statistical Analysis Plan the intention-to-treat (ITT) population (all randomized participants analyzed according to the randomized assignment)-the primary analysis set; the per-protocol (PP) population (participants with ≥80% treatment compliance and no major protocol violations)-used for confirmatory efficacy consistency testing; and the safety analysis (SA) population (all randomized participants exposed to the investigational product or placebo with post-intervention safety data)-used for all safety evaluations.

Primary Outcome Analysis Due to the asymptomatic nature of colorectal adenoma recurrence, which can only be detected at scheduled annual colonoscopic examinations, the time to recurrence is considered interval-censored data (i.e., the exact recurrence time is unknown, only that it occurred within a 12-month window between two consecutive colonoscopies). Given this data characteristic, the 3-year cumulative CRA recurrence rate will be estimated using the life table method, which divides follow-up time into 12-month intervals (0-12, 12-24, 24-36 months). Between-group comparisons of recurrence-free survival will be performed using the stratified log-rank test (stratified by participating center). Hazard ratios (HR) and corresponding 95% confidence intervals (CIs) will be estimated using a stratified Cox proportional hazards model. To ensure the robustness of the findings, sensitivity analyses using the Turnbull algorithm (an extension of the Kaplan-Meier method for interval-censored data) will also be conducted.

Interventions

• Drug Clostridium butyricum capsules, Live
  Oral Clostridium butyricum capsules, Live: take 3 capsules twice daily (bid) for the first 3 months after adenoma resection, then continue with 3 capsules once daily (qd) until 3 years post-resection (each capsule contains ≥6.3 × 10⁶ CFU of Clostridium butyricum).
• Other Control (placebo)
  Placebo capsules containing corn starch, with identical appearance, weight, and administration method as the treatment group.

Primary outcome measures

• The 3-year cumulative recurrence rate of CRA [Time frame: 3 years]

Secondary outcome measures (8)

• 1-year and 2 year adenoma recurrence rate [Time frame: 1-year and 2-year after enrollment]
• incidence of colorectal cancer [Time frame: 3 years after enrollment]
• Incidence of advanced colorectal adenomas [Time frame: 3 years after enrollment]
• Location of adenoma recurrence [Time frame: 3 years]
• Number of recurrent adenomas [Time frame: 3 years]
• Histological classification of recurrent adenomas [Time frame: 3 years]
• Size of recurrent adenomas [Time frame: 3 years]
• adenoma burden [Time frame: Assessed at 12, 24, and 36 months post-enrollment]

Eligibility criteria

Inclusion criteria

• Age between 18 and 75 years
• No restriction on sex
• Boston Bowel Preparation Score (BBPS) ≥ 7 prior to endoscopic procedure
• Completed endoscopic resection of colorectal adenomas (including cold snare polypectomy, ESD, EMR, etc.) with no residual adenomas or polyps observed endoscopically
• Histologically confirmed adenomas (including tubular, villous, or tubulovillous types) without malignant transformation
• Able to take oral medication
• Signed informed consent

Exclusion criteria

• Use of probiotics, prebiotics, synbiotics, or antibiotics within 2 weeks prior to enrollment
• Presence of psychiatric disorders or other conditions preventing compliance with the intervention
• Dysfunction of vital organs (liver, kidney, heart, etc.) deemed unsuitable for clinical study participation after evaluation
• Participation in other clinical trials within 3 months prior to enrollment
• History of gastrointestinal surgery (excluding endoscopic procedures)
• History of inflammatory bowel disease
• History of autoimmune diseases
• Long-term use of aspirin (≥100 mg/day for over 3 months) or calcium supplements (≥1200 mg/day for over 3 months)
• Pregnancy or breastfeeding
• Previous treatment for colorectal adenomas (including endoscopic or surgical resection)
• Familial adenomatous polyposis (FAP)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

China · 2 centers

• the Affiliated Hospital of QIngdao University — Qingdao
• Weifang People's Hospital — Weifang

Identifiers

NCT: NCT07167342 · GISSG2026-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗