Colorectal NeoplasmsNCT05592886
A Novel Oral Synbiotic Formula in Reducing Advanced Adenoma Recurrence and Colorectal Neoplasia-related Bacterial Gene Markers
A study testing SMT04 formula in people with Colorectal Neoplasms and Colorectal Adenoma, run by Chinese University of Hong Kong at 2 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Colorectal Neoplasms, Colorectal Adenoma, Colorectal Cancer
- What is being tested?
- SMT04 formula
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 649 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 15 Dec 2022to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
China1 site, 1 recruiting
- Not yet recruiting
Inner Mongolia People's Hospital
Hohhot, Inner Mongolia
Guijun Prof. Zhao, MD, 0471-3283258, cnzhaoguijun@163.com
Guijun Prof. Zhao, MD
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital
Hong Kong
Louis Lau
About this study
Official title: 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.
Read the 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.
- Being tested
- SMT04 formula, Active placebo
- Keywords
- Adenoma recurrence, Bacterial marker
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SMT04 formulaOther
The SMT04 formula is a synbiotic containing probiotics and prebiotics
Active placeboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Receive SMT04 formula Receives: Other: SMT04 formula |
| Placebo arm | Placebo comparator | Receive active placebo Receives: Other: Active placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Secondary outcomes (6)
Incidence of recurrent colorectal adenomas at year 1
The proportion of patients with metachronous recurrent adenoma at year 1
Measured: 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
Measured: 1 year
Number of recurrent adenomas at year 1
The number of recurrent colorectal adenoma per patient both in intervention and placebo arm
Measured: 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
Measured: 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
Measured: 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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2022
- Study start15 Dec 2022
- Primary completion15 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 649 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Inner Mongolia People's Hospital
- Responsible party
- Principal investigator, Louis Ho Shing Lau, Chinese University of Hong Kong
- Investigators
- Louis Lau, Principal investigator, Prince of Wales Hospital, Shatin, Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05592886
- Sponsor's protocol ID
- 2022.360
- Status last verified
- Jul 2025
- First submitted
- 17 Oct 2022
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05592886
- Acronym / sponsor ID
- 2022.360
- Keywords
- Adenoma recurrence, Bacterial marker
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 649 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Collaborators
- Inner Mongolia People's Hospital
- Study start
- 15 Dec 2022 (actual)
- Primary completion
- 15 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 25 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Other: SMT04 formulaReceive SMT04 formula |
| Placebo arm | Placebo comparator | Other: Active placeboReceive active placebo |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SMT04 formulaThe SMT04 formula is a synbiotic containing probiotics and prebiotics | Other | Intervention arm |
| Active placeboThe 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. | Other | Placebo arm |
Primary outcome
The incidence of metachronous recurrent advanced colorectal neoplasia at year 1 (local or at other sites).
Time frame: 1 year
The proportion of patients with metachronous recurrent advanced neoplasia at year 1
6 secondary outcomes
Incidence of recurrent colorectal adenomas at year 1
Time frame: 1 year
Number of recurrent advanced neoplasia at year 1
Time frame: 1 year
Number of recurrent adenomas at year 1
Time frame: 1 year
Changes in the levels of bacterial gene markers
Time frame: 1 year
Correlation between recurrent advanced colorectal neoplasia and the changes in levels of bacterial gene markers
Time frame: 1 year
Correlation between recurrent adenoma and the changes in levels of bacterial gene markers
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Louis Lau principal investigator
Prince of Wales Hospital, Shatin, Hong Kong
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SMT04 formula in people with Colorectal Neoplasms and Colorectal Adenoma, run by Chinese University of Hong Kong at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China, Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Louis Lau (35052211, louishslau@cuhk.edu.lhk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of metachronous recurrent advanced colorectal neoplasia at year 1 (local or at other sites). (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2025.