ASsoCiation bEtween seRum and Tissue protein profiles in pAtients wIth iNflammatory bowel disease: the ASCERTAIN trial

Inflammatory bowel disease (IBD) comprise two major entities of chronic
intestinal disorders: Crohn*s disease (CD) and ulcerative colitis (UC). The
ongoing expansion in the therapeutic armamentarium for IBD has improved
therapeutic outcome for many patients. However, both CD and UC are highly
heterogenic conditions, both in clinical presentation and in response to
therapy. It remains difficult to predict which patient is likely to respond to
a particular treatment at any given stage of their disease. To optimize the use
of currently available therapeutic interventions, a more personalized
diagnostic and therapeutic care-path is needed. Currently it may take several
years to find an effective treatment for an individual patient. Hence, from
both a patient and a pharmaco-economic point of view, predictive biomarkers for
therapy response would be of great benefit.
Most studies that aimed to discover new IBD biomarkers on a protein level have
mainly focused on plasma/serum. However, recent studies suggest that analysing
material closer to or directly from the location of disease may yield higher
concentrations of potential biomarkers. However, although the diseased
intestine itself may contain increased protein concentrations and facilitate
biomarker discovery, the use of this material in routine care is limited due to
the invasive nature of the procedure. Therefore, matched validation of
candidate markers in serum is required. We aim to investigate the correlation
between the protein profiles of the serum and the gut mucosa.

1. Primary objective:
1.2 To assess the correlation of protein profiles between intestinal tissue and
serum in patients with IBD

2. Secondary Objectives:
2.1 To identify the source matrix that has the highest chance to yield
clinically relevant IBD biomarkers in future research
2.2 To identify putative candidate biomarkers that are able to:
2.2.1 differentiate between IBD and non-IBD controls
2.2.2 differentiate between CD and UC
2.2.3 identify subgroups within the patients groups of CD or UC in alignment
with endoscopic severity.
2.3 To identify possible targets for the future development of therapeutic
compounds

Prospective multi-centre cross-sectional study

This trial will consist of two phases:

1. Prospective inclusion of 80 IBD patients (40 CD and 40 UC) with active
disease and 12 non-IBD patients.
1.1 Collection of 1 serum tube (5mL) prior to endoscopy
1.2 Collection of 5 mucosal biopsies of diseased gastrointestinal tissue

2. Analysis phase:
2.1 Utilising OLINK bioscience *Proseek Multiplex Inflammation Panel*, both
the serum and intestinal tissue protein profile will be defined.
2.2 Assess the correlation between the protein profiles of the intestinal
tissue and the serum

This is a cross-sectional trial comprising only one time point of intervention.
The burden and risks for patients are negligible. Briefly, 5 mL of blood will
be drawn prior to start of endoscopy. No phlebotomy is needed as an intravenous
line is already in place for medication administration. Five endoscopic
biopsies are taken during endoscopy which include a minimal risk of
complications, mainly bleeding or perforation (<1:10,000) [1]. In case a
complication occurs, endoscopic treatment (hemostasis/clipping) is effective in
most cases. Rarely, hospital admission with/without surgical intervention,
antibiotic therapy and/or blood transfusion can be required.

1. Yao, M.D., et al., Multiple endoscopic biopsies in research subjects: safety
results from a National Institutes of Health series. Gastrointest Endosc, 2009.
69(4): p. 906-10.