Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000976583
Ethics application status
Approved
Date submitted
3/07/2024
Date registered
12/08/2024
Date last updated
12/08/2024
Date data sharing statement initially provided
12/08/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Interaction of human gut microbiota and local immune system in health and progression of colorectal adenoma (MIMICA-1)
Scientific title
Colorectal adenoma-carcinoma sequence rediscovered: interaction of human gut microbiota and local immune system in health and carcinogenesis in adult patients
Secondary ID [1] 312445 0
Lithuanian Research Council; P-MIP-22-315
Universal Trial Number (UTN)
Trial acronym
MIMICA-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal cancer (adenocarcinoma) 334272 0
Colorectal adenoma (simple and advanced) 334273 0
Colorectal carcinoma in situ 334274 0
Condition category
Condition code
Cancer 330935 330935 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Participants: adult patients diagnosed with colorectal (CR) polyps, with data collected from the following 4 groups: (1) adenoma up and equal to 1 cm in diameter, (2) adenoma larger than 1 cm in diameter,(3) carcinoma in situ, (4) adenocarcinoma; and healthy patients as a (5)th control group.
Observational data collection: at first, all participants will have their feces collected prior to bowel preparation for colonoscopy or surgery. This will be performed from 2 weeks until the day of planned procedure. Thereafter, as a common management, and depending on specific colorectal dysplasia found, patients will receive either endoscopic polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), transanal endoscopic microsurgery (TEM), or bowel resection. During the procedure additional observational material will be collected for the study, i.e. bowel biopsy specimens from right- and left-sided colon, terminal ileum, and pathologic lesion, if present. Bowel sampling will take one day and the same patient’s visit for the planned interventional procedure of colorectal lesion removal. Therefore, data will be taken twice, once bowel tissue specimens collected at the mentioned procedure and one fecal sample collected two weeks beforehand.
Intervention code [1] 328951 0
Not applicable
Comparator / control treatment
Four exposure groups according to the CR neoplasia size and the dysplasia level (adenoma up and equal to 1 cm in diameter; adenoma larger than 1 cm in diameter; carcinoma in situ, adenocarcinoma, and 4 self-control groups (where patient's control biopsy samples from healthy site of the colon serves as his own control), plus the fifth general control group (where biopsies of healthy terminal ileum and right-, left- sided healthy colon, as well as fecal samples) will be taken from healthy patients (those without any polypoid lesions found during colonoscopy).
Control group
Active

Outcomes
Primary outcome [1] 338697 0
Lumen microbiota composition
Timepoint [1] 338697 0
Post-procedure phase at start and end of week 3 (t3-t3) at the project's timeline.
Primary outcome [2] 338700 0
Mucosa-associated microbiota composition (a composite outcome: composition at healthy bowel: terminal ileum, right- and left-sided colon; and at dysplastic lesion site, if present)
Timepoint [2] 338700 0
Post-procedure phase during week 3 and week 4 (t3-t4) at the project's timeline.
Primary outcome [3] 338702 0
Composite outcome: count, density, and distribution of immunocompetent (CD3, CD8, CD20, CD68) cells in epithelial and stromal compartments of tissue specimens from healthy bowel (terminal ileum, right- and left-sided colon) and dysplastic lesion site, if present).
Timepoint [3] 338702 0
Post-procedure phase from week 1 to week 2 (t1-t2)
Secondary outcome [1] 437895 0
Nil
Timepoint [1] 437895 0
Nil

Eligibility
Key inclusion criteria
Exposure groups:
(1) Patients with histologically confirmed dysplastic colorectal lesion: early and advanced-adenoma, carcinoma in situ or adenocarcinoma (advanced adenomas are defined as those with high-grade dysplasia, villous or tubulovillous histology, equal to or greater than 1 cm in diameter);
(2) Adult patients;
(3) Written informed consent.

Control (healthy) group:
(1) Healthy patients (without any polypoid lesions found during screening colonoscopy)
(2) Adult patients;
(3) Written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria
(1) Patients under the age of 18 years;
(2) Confirmed serrated (sessile serrated (SSA), traditional serrated adenomas (TSA)) or hyperplastic polyps or non-polypoid lesions;
(3) Signs of colorectal tumor obturating the lumen of the bowel which would limit complete colonoscopy;
(4) Suffer from other gastrointestinal tumors;
(5) Pregnancy;
(6) Previous colon resection;
(7) History of surgery disrupting gastrointestinal tract integrity;
(8) History of inflammatory bowel disease (ulcerative, Crohn’s, radiation-induced, or infectious colitis or other previous chronic inflammatory illnesses);
(9) Familial adenomatous polyposis (FAP) or other hereditary colon syndromes;
(10) Clinically significant immunodeficiency;
(11) Evidence of infection;
(12) During the last year patient had:
- suffered from Cl. difficile colitis or was a carrier of Cl. difficile; suffered from salmonellosis or other gastrointestinal infection;
- a long-term (> 6 months) use or recently completed therapeutic antibiotic course within the last month;
- corticosteroid and/or immunosuppressant therapy;
- received chemo- or radiation therapy in the abdomen and/or pelvis chemotherapy;
- regular use (> 3 months) of pre-/pro-/(sin)biotics and/or statins;
- a long-term (> 6 months) use of proton pump inhibitors;
(13) Patients who cannot undergo colonoscopy on time and cannot cooperate fully.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis
The sample size is estimated based on the data from previous clinical trial, where 10 participants per group had 80% power at an alpha level of 0.05 and beta level of 0.2 to detect significant differences. The sample size in this study was calculated statistically by G*Power 3.1.9.4. Considering the expected withdrawal of participants during the intervention, we plan to recruit from 10 to 15 participants per group.
Statistical methods include: continuous data will be expressed as mean ± standard deviation (SD). Categorical data will be expressed as the number of cases (n) and percentage (%). If the data is not normally distributed (demonstrated by the Shapiro-Wilk test), quantitative variables among the groups will be compared using a Kruskal-Wallis test. Post hoc comparisons of pairwise differences between two groups will be evaluated by the Unpaired t-test, F-test and Mann-Whitney U-test using the modified Bonferroni procedure for multiple comparison adjustment.
As for analysis of microbial data, relative abundances, alpha and beta diversity will be performed. Principal Coordinates Analysis (PCoA) will be executed after calculating Bray-Curtis dissimilarity and UniFrac distances between samples. Beta diversity analyses will involve the application of Hellinger transformation to account for the compositional nature of microbiome data. Cluster analysis will be performed using Analysis of Similarities (ANOSIM) to assess the significant differences in microbial community composition between sample groups. Redundancy analysis will be used to identify factors that influence the structure of the microbiome. Alpha diversity will be calculated through the Shannon index, Simpson index, and Chao1 metrics after appropriate rarefaction. For the identification of differences in specific taxa between groups, ANCOM and LEfSe analysis will be conducted.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
14/02/2023
Date of last participant enrolment
Anticipated
Actual
31/07/2024
Date of last data collection
Anticipated
30/08/2024
Actual
Sample size
Target
50
Accrual to date
Final
54
Recruitment outside Australia
Country [1] 26406 0
Lithuania
State/province [1] 26406 0

Funding & Sponsors
Funding source category [1] 316862 0
Government body
Name [1] 316862 0
Research Council of Lithuania
Country [1] 316862 0
Lithuania
Primary sponsor type
University
Name
Vilnius University Faculty of Medicine
Address
Country
Lithuania
Secondary sponsor category [1] 319099 0
None
Name [1] 319099 0
Address [1] 319099 0
Country [1] 319099 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315621 0
Vilnius Regional Bioethics Committee (Lithuania)
Ethics committee address [1] 315621 0
Ethics committee country [1] 315621 0
Lithuania
Date submitted for ethics approval [1] 315621 0
12/04/2022
Approval date [1] 315621 0
12/04/2022
Ethics approval number [1] 315621 0
2022/4-1422-902

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135286 0
Prof Tomas Poskus
Address 135286 0
Vilnius University Hospital Santaros Klinikos, Santariskiu st.2, 08406 Vilnius, Lithuania
Country 135286 0
Lithuania
Phone 135286 0
+370 68862669
Fax 135286 0
Email 135286 0
[email protected]
Contact person for public queries
Name 135287 0
Jurate Valciukiene
Address 135287 0
Vilnius University Hospital Santaros Klinikos, Santariskiu st.2, 08406 Vilnius, Lithuania
Country 135287 0
Lithuania
Phone 135287 0
+370 68862656
Fax 135287 0
Email 135287 0
[email protected]
Contact person for scientific queries
Name 135288 0
Tomas Poskus
Address 135288 0
Vilnius University Hospital Santaros Klinikos, Santariskiu st.2, 08406 Vilnius, Lithuania
Country 135288 0
Lithuania
Phone 135288 0
+370 68862669
Fax 135288 0
Email 135288 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.