To test the hypothesis that vedolizumab has chemopreventive properties with regard to colorectal neoplasia in the high-risk group of patients with PSC/IBD.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Hepatic and hepatobiliary disorders
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Differences in expression of previously identified potential biomarkers with
regard to copy number changes, cancer-relevant gene mutations, methylation
status, as well as MIF expression in patients with PSC/IBD versus IBD,
stratified by vedolizumab treatment.
Secondary outcome
IIa) Evaluation of potential markers in peripheral blood samples in order to
evaluate clinical applicability of the potential markers.
IIb) Differences between PSC/IBD and IBD in the identified gene alterations.
Background summary
Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory disease of
the biliary tree of unknown cause. Therapy is still limited to treatment of
complications, and ultimately leading to bile duct destruction and liver
failure. PSC has a strong association with inflammatory bowel disease (IBD),
especially ulcerative colitis (UC). The gut homing lymphocyte paradigm offers a
plausible explanation linking the gut and liver in PSC, stating that gut-primed
t-lymphocytes (expressing α4β7) can migrate into the liver because of
aberrantly expressed adhesion molecules (like MAdCAM-1) and chemokines in the
liver. Vedolizumab is a humanized monoclonal antibody, that specifically binds
to the lymphocyte integrin α4β7, thereby impairing the migration of gut-homing
lymphocytes into gastrointestinal mucosa and possibly into the liver.
The risk of developing colorectal carcinoma (CRC) is elevated in patients with
PSC and concomitant IBD compared to patients with IBD alone, with an estimated
cumulative risk of 13% after 30 years. This mandates annual colonoscopic
surveillance from the date of diagnosis of PSC, which is a burden for the
patients. A clinically useful biomarker assay for early detection of the
dysplasia-carcinogenesis sequence could help in surveilling these patients.
Previous research showed an increased expression of Macrophage Migration
Inhibitory Factor (MIF) in right colonic mucosal tissue of PSC/IBD patients as
opposed to IBD-patients. In gastrointestinal cancers, an increase of this
inflammatory cytokine is seen. Blocking T-cell influx into the colonic tissue
could possibly decrease MIF levels in the colonic mucosa, vedolizumab may play
a role in this process.
Study objective
To test the hypothesis that vedolizumab has chemopreventive properties with
regard to colorectal neoplasia in the high-risk group of patients with PSC/IBD.
Study design
Prospective observational study.
Study burden and risks
Patients will be recruited from the outpatient clinic and followed for 3 years.
During surveillance colonoscopies (2 or 3 subsequent time points, depending on
the planned colonoscopies), an additional 8 biopsies will be obtained in
addition to routine serial biopsies. Prior to the first colonoscopy, blood will
be drawn. Faeces will be collected prior to each colonoscopy.
Colon biopsies taken during colonoscopy include a minimal risk (risk of
complications <1:1000). In case of a complication, such as a perforation or
bleeding, the consequence is hospital admission, antibiotic therapy or blood
transfusion.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Group 1:
- Diagnosis of Primary Sclerosing Cholangitis and concommitant diagnosis of
Inflammatory bowel disease, Group 2:
- Diagnosis of inflammatory bowel disease
- 10 patients with routine vedolizumab treatment, 10 patients without
vedolizumab treatment , Both groups:
- Age 18 years and older, either male or female
- Ability to give informed consent
- Groups will be stratified for the use of thiopurines
- Groups will be stratified for UC, CD and IBDU
Exclusion criteria
- Medical history of proctocolectomy
- Use of biologic therapy other than vedolizumab within 8 weeks of enrolment
- Inability to give informed consent
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL59904.018.16 |
| OMON | NL-OMON26884 |