Ulcerative Colitis Clinical Trial
Official title:
The Value of Virtual Chromoendoscopy With i-SCAN and Confocal Laser Endomicroscopy in the Assessement of Dysplasia on Patients With Inflammatory Bowel Disease
Recently, Confocal Laser Endomicroscopy (CLE) has been developed as a novel technique that actually enables in vivo microscopic analysis of the gastrointestinal tract, during ongoing endoscopy. The potential role of CLE has been explored in pathology of both upper and lower gastrointestinal tract, showing good accuracy for predicting the final histopathological diagnosis, based on immediate evaluation of tissue and vascular patterns. Because of its minute scanning area, this techology is best used in conjunction with other "red-flag" techniques to screen the mucosa for areas of interest, which can then be examined by CLE for a histological diagnosis. I-scan technology (Pentax, Tokyo, Japan) is a new image-enhanced endoscopic technique that can achieve a virtual chromoendoscopy, but until now there have been no studies to determine the role of this technology in the evaluation of activity in inflammatory bowel disease. The study protocol is based on comparing imaging findings of p-CLE in conjunction with I-scan endoscopy with activity score and histological diagnosis of inflammatory bowel disease. CLE might have an important role in IBD patients management, by assessing the inflammation, dysplasia or response to treatment.
The value of I-Scan and Confocal Laser Endomicroscopy for the assessment of chronic
inflammatory bowel disease
Background Colonoscopy plays an important role in the diagnosis, assessment of activity,
extension and response to therapy in chronic inflammatory bowel disease (IBD). Conventional
examination underestimates extent and activity of the disease compared with histology,
therefore, mucosal biopsy is a critical component of endoscopic examination of these
patients. Taking multiple biopsies is time consuming, carries a low but not negligible risk
of secondary hemorrahage, and causes a delay in diagnosis, whilst awaiting histological
analysis.
Confocal laser endomicroscopy has emerged in recent years as a novel technique that actually
enables in vivo microscopic analysis during ongoing endoscopy. Endomicroscopy can be
performed either with a dedicated endoscope (eCLE) or with miniprobe-based systems (pCLE)
[1]. It is a contrast based technique, the most widely used agent being the intravenously
administered fluorescein [2]. The probe-based endomicroscopy system consists of a flexible
catheter probe representing a bundle of optical fibers linked to a micro-objective, a laser
scanning unit and the control and acquisition software (Cellvizio; Mauna Kea Technology,
Paris, France). The flexible confocal miniprobes were specifically designed to be passed
through the working channels of standard endoscopes, biliary catheters or cholangioscopes and
thus the pCLE system can be easily integrated into any endoscopy unit. The principle of the
technique is based on a laser beam of defined wavelength being focused towards the targeted
tissue and the recaptured signal is displayed as 'optical biopsies' in a single horizontal
plane.
The potential role of CLE has been explored in pathology of both upper and lower
gastrointestinal tract, showing good accuracy for predicting the final histopathological
diagnosis based on immediate evaluation of tissue and vascular patterns [3]. Because of its
minute scanning area, this techology is best used in conjunction with other "red-flag"
techniques to screen the mucosa for areas of interest, which can then be examined by CLE for
a histological diagnosis [4].
I-scan technology (Pentax, Tokyo, Japan) is a new image-enhanced endoscopic technique,
consisting of three types of algorithms: surface enhancement (SE; enhancement of the
structure through recognition of the edges), contrast enhancement (CE; enhancement of
depressed areas and differences in structure through colored presentation of low density
areas) and tone enhancement (TE; enhancement tailored to individual organs through
modification of the combination of RGB components for each pixel) [5,6]. Like narrow band
imaging i-scan can achieve a virtual chromoendoscopy, but until now there have been no
studies to determine the role of this technology in the evaluation of activity in
inflammatory bowel disease [7].
Aim of the study The aim of the study is to compare imaging findings of p-CLE in conjunction
with I-scan endoscopy with activity score and histological diagnosis.
Patients and methods The study will prospectively include patients with active ulcerative
colitis or Crohn's disease who meet the inclusion and exclusion criteria. All patients will
be examined by conventional colonoscopy, followed by I-scan examination and p-CLE, and biopsy
samples will be taken for each segment of the colon. Then, the correlation between histology
as "gold standard", activity score (Mayo score for ulcerative colitis, respectively Crohn's
Disease Activity Index for Crohn's disease) and imaging findings will be calculated for both
pathological and normal areas.
Inclusion criteria
- Age > 18 years old, male or female
- Patients diagnosed with active ulcerative colitis (MAYO score >3) or Crohn's disease
(CDAI score >150), where an indication for treatment and colonoscopy exists. Newly
diagnosed as well as patients already on oral 5-ASA therapy, may be included.
- Signed informed consent for colonoscopy and p-CLE examination Exclusion criteria
- Failure to provide informed consent
- Patients with a contraindication to colonoscopy
- Known allergy to fluorescein
- Pregnant or breast-feeding patients
- Ongoing systemic immunosuppressive therapy with prednisolone, azathioprine or biological
agents.
Data collected for each participant will include:
- Personal data (name, surname, age, sex)
- Results from previous investigations
- Clinical evaluation (stools frequency, rectal bleeding, fever, abdominal pain, extra
intestinal manifestation, abdominal mass) and blood count for activity index calculator
(Mayo score for ulcerative colitis, respectively CDAI score for Crohn disease)
- Endoscopic findings
- Histological and immunohistochemical findings
- Molecular analysis findings
Imaging tests
- All patients will be examined by I-scan colonoscopy and the degree and distribution of
the acute inflammation will be assessed.
- p-CLE examination will follow, after the intravenous administration of the contrast
agent (2.5 ml fluorescein 10%), in every segment of the colon in both normal and
pathological areas.
- Image data will be stored digitally for offline analysis (10-20 seconds movie for each
area examined).
- Biopsy samples will be taken from each area examined by p-CLE for histological,
immunohistochemical and molecular analysis.
The biological material collected during the study (this will include one ml of whole blood
and tissue biopsies from normal tissue and from modified areas of 2 to 3 mm each) will be
frozen and stored. When the expected number of participants is reached the samples will
undergo molecular studies for assessing the markers of angiogenesis as detailed further in
the protocol. The biological materials will be stored and analyzed during an estimated time
of 18 months from the start of the trial. After completion of the study the biomaterials will
be disposed of.
Biological samples for molecular tests:
- Blood samples will be collected before imaging procedures
1. For DNA extraction 2-5 ml of blood can be collected in tubs containing EDTA and
stored at 4°C for a day or transferred to -80°C freezer for longer storage
2. For RNA extraction 2-5 ml of blood must be collected in PAX tubs and kept maximum 2
hours at room temperature and then transferred to -80°C freezer for longer storage
- Tissue samples:
Possible methods to stabilize tissue samples for further molecular analysis
(RNA/DNA/protein):
1. 0,3-0,5 cm of tissue is stored immediately in a tube containing RNAlater Solution for
approximately 24 hours at 4°C; after this the RNAlater solution is taken out from the
tube (under sterile conditions) and the sample is frozen at -80°C until RNA/DNA
extraction.
2. 0,3-0,5 cm of tissue is stored immediately in an empty cryogenic tube and thrown in a
container that contains liquid nitrogen or dry ice with methanol.
Primary Outcome Measures:
- p-CLE findings are recorded and compared with the findings of conventional colonoscopy
and I-scan colonoscopy.
- p-CLE and I-scan colonoscopy findings are compared with the pathological evaluation of
tissue samples.
Secondary Outcome Measures:
- Effect of therapy, based on the results of the conventional colonoscopy, I-scan and
p-CLE
- Registering time of the procedure.
- Registering possible complications
Risks and side effects Complications may occur during colonoscopy, but they are rare. These
consist of bleeding at the biopsy site which is usually minimal, self-limited and rarely
requires follow-up. Perforation of the bowel is extremely rare. The safety profile of the
contrast agent (fluorescein) showed a very low incidence of side effects. It is not
nephrotoxic and the incidence of hypersensitivity or severe allergic events is low.
Fluorescein is approved for clinical use in EU countries.
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