Colorectal Adenoma, Probiotics
Conditions
Keywords
Colorectal Adenoma, Clostridium butyricum
Brief summary
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
DRUGClostridium 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).
OTHERControl (placebo)
Placebo capsules containing corn starch, with identical appearance, weight, and administration method as the treatment group.
Sponsors
The Affiliated Hospital of Qingdao University
Shandong Cancer Hospital and Institute
Yantai Yuhuangding Hospital
Rizhao People's Hospital
Qianfoshan Hospital
Weifang People's Hospital
Dongying People's Hospital
Peking University People's Hospital
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
The First Affiliated Hospital of Bengbu Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The 3-year cumulative recurrence rate of CRA | 3 years | The 3-year cumulative recurrence rate of CRA following colonoscopic resection. Recurrence is defined as the identification of new or residual adenomatous polyps in the colorectum on colonoscopy during the follow-up period, confirmed pathologically. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1-year and 2 year adenoma recurrence rate | 1-year and 2-year after enrollment | Each subject will undergo a colonoscopy once per year after enrollment to monitor for adenoma recurrence. |
| incidence of colorectal cancer | 3 years after enrollment | Each subject will undergo a colonoscopy once per year after enrollment to monitor for the development of colorectal cancer. The incidence of colorectal cancer is calculated as: Incidence (%) = (Number of subjects diagnosed with colorectal cancer / Total number of subjects) × 100% |
| Incidence of advanced colorectal adenomas | 3 years after enrollment | Each subject will undergo a colonoscopy once per year after enrollment to monitor for the presence of advanced adenomas. The incidence of advanced adenomas is calculated as: Incidence (%) = (Number of subjects with advanced adenomas / Total number of subjects) × 100% Advanced colorectal adenoma is diagnosed when any of the following criteria are met: Adenoma diameter ≥ 10 mm，Villous component ≥ 25%，Presence of high-grade intraepithelial neoplasia. |
| Location of adenoma recurrence | 3 years | Classify the locations according to ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. |
| Number of recurrent adenomas | 3 years | — |
| Histological classification of recurrent adenomas | 3 years | Classify the locations according to Tubular adenoma, Villous adenoma, Tubulovillous adenoma, Serrated adenoma |
| Size of recurrent adenomas | 3 years | Measure the maximum diameter of the adenoma in millimeters |
| adenoma burden | Assessed at 12, 24, and 36 months post-enrollment | Adenoma burden: the sum of the maximum diameters of all recurrent adenomas detected during follow-up. |
Countries
China
Contacts
CONTACTGan Liu
CONTACTyanbing Zhou
STUDY_CHAIRyanbing Zhou
The Affiliated Hospital of Qingdao University
Outcome results
None listed