To identify pathogenic bacterial biofilms in UC-patients with and without neoplasia in tandem with host factors such as barrier defects and carcinogenic pathway activation in a prospective cohort study.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Via the treating physician, patients scheduled for colonoscopy will be
approached to participate in the study. Written information will be provided by
mail, including informed consent forms, tubes for fecal collection and a short
questionnaire. When written informed consent is obtained, biopsies will be
collected from the patients. From healthy controls 3 biopsies from the left and
3 biopsies from the right sided colon will be collected. From UC patients,
biopsies from healthy (2 extra biopsies), inflamed (2 extra biopsies) and
suspected neoplastic lesions (2 extra biopsies) will be collected during
scheduled colonoscopy. Tissue will be fixed in formalin (routine diagnostics)
for pathology evaluation, snap frozen for DNA isolation and fixed in methacarn
for biofilm analysis.
1) we will identify the bacterial biofilms in direct contact with the colon and
assess whether bacteria invade the epithelium and colonic crypts (Methacarn
fixed biopsies)
2) we will excise the bacterial biofilms with a laser-capture technique to
identify the presence and expression of carcinogenic bacterial toxins within
the biofilm (Methacarn fixed biopsies)
3) we will assess whether the presence of pathogenic bacteria or toxins are
associated with oncogenic transition of the tissue by examining bacterial
defense proteins, epithelial barrier function and activation of
pro-carcinogenic signaling pathways. (formalin fixed biopsies)
4) we will identify bacteria or bacterial traits that can predict neoplastic
lesions in UC-patients (snap frozen biopsies). The findings will be validated
with DNA isolated from stool.
Anticipated results: Insight in the relevance of pathogenic bacteria in
biofilms in UC-patients during neoplasia development. A better understanding of
CAC-pathogenesis will provide new tools for CAC prevention and diagnosis in
patients with chronic UC. The results from this study do not have any
implications for regular patient care and are solely of value for research
purposes.
Secondary outcome
nvt
Background summary
In the Netherlands approximately 35.000 patients suffer from ulcerative colitis
(UC), a disease characterized by chronic inflammation due to an abnormal
response to bacteria. Especially UC-patients with a long duration of disease
(>10 years) have an increased risk of colitis-associated cancer (CAC). Although
there is accumulating evidence that chronic inflammation promotes CAC, the
cellular and microbial mechanisms contributing to this process are still
unclear. We propose that pathogenic pro-oncogenic microbes in bacterial
biofilms (a plaque of bacteria) can drive CAC-development and thus contribute
to an increased risk for CAC; biofilms can shield pathogenic microbes from
attack by the immune system and provide a harbor in which they can thrive and
promote cancer.
Study objective
To identify pathogenic bacterial biofilms in UC-patients with and without
neoplasia in tandem with host factors such as barrier defects and carcinogenic
pathway activation in a prospective cohort study.
Study design
This is a prospective cohort study in patients with ulcerative colitis and a
control group that undergo routine colonoscopy evaluation within the
Gastroenterology department. All relevant clinical data will be collected in
case report forms (Castor) via patient files and a short questionnaire. The
patients will be asked to provide a stool sample. Colonic biopsies will be
collected for pathology evaluation (routine diagnostics), biofilm assessment
and microbial sequencing analysis.
Study burden and risks
There exists a minimal risk for bleeding associated with taking biopsies during
colonoscopy. The perforation risk after taking biopsies is negligible. The risk
for bleeding (about 2%) or perforation (about 0.01 to 0.1 %) after removing
polyps is far larger than taking simple superficial biopsies as is the case in
this study. Biopsies are only taken from the mucosa and will not reach the
deeper layers of the colon as is for example the case when removing polyps with
diathermy. Furthermore, also colonoscopies without taking biopsies or polyp
removal give a risk of perforation that is comparable to colonoscopies with
taking biopsies (0.6 per 1000 procedures). In this procedure colonoscopy is
part of regular patient care and only taking the biopsies is part of the study.
Therefore the additional risk of taking biopsies for this study is estimated to
be very small.
Geert Grooteplein Zuid 24
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 24
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
For ulcerative colitis (N<=80):
* Left-sided colitis or pancolitis (Montreal score E2 or E3)
* > 8 years of disease duration
* At time of colonoscopic surveillance in clinical remission (Montreal score S0);For controls (N<=40):
* Routine scheduled colonoscopy for iron deficiency anemia, changed stool pattern, irritable bowel syndrome or status post-diverticulitis
* no abnormal findings during colonoscopy
Exclusion criteria
Exclusion criteria for UC-patients and controls:
* Oral antibiotics in last 3 months before colonoscopy (drastically affects the mucosal microbiota);Exclusion criteria for controls only:
* No history of CRC and UC or other inflammatory disease of the intestine
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL55930.091.16 |