Clinical trial NCT01861288: Deep Endoscopic Remission Assessed by a Surrogate Biomarker in Patients With Inflammatory Bowel Disease
Official title: Development of a New Algorithm to Determine the Activity of Disease: Deep Endoscopic Remission Assessed by a Surrogate Biomarker in Patients With IBD.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Disease
Crohn Disease
Ulcerative Colitis
Keywords: Inflammatory Bowel Disease
Fecal Calprotectin
Clinical IBD score (SCCAI, PUCAI, aPCDAI)
Endoscopic deep remission
Histopathologic deep remission
Immunological deep remission
Treatment algorithm
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: University Hospital of North Norway
name: Hvidovre University Hospital
First posted: 2013-05-23
Enrollment: 157
Sex: ALL
Maximum age (years): 67
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study includes adult and pediatric patients with and without IBD who, as part of an ongoing investigation or treatment, have to undergo a sigmoidoscopy (for children: colonoscopy).

Brief summary: We hypothesize that the number of needed endoscopic procedure performed at IBD patients (adult and children), can be reduced by using an individualized algorithm of symptoms, blood and faecal biomarkers.

The aim of the study is to reduce the numbers of endoscopies, as the procedure is uncomfortable for the patient, time consuming and expensive. Through indirect tests - blood test, fecal inflammation marker and clinical symptoms - compared to endoscopic findings, we want to construct an algorithm by which the intestinal healing can be foreseen without performing an endoscopy.

Furthermore, we will correlate FC, blood tests, clinical symptom score and endoscopic score, with the histo-pathological inflammation score from intestinal biopsies and the immunological score depicted by TNF- alpha and IL17A levels in intestinal tissue, in order to assess the gold standard - endoscopic remission.

Detailed description: Deep remission: The treatment goal in patiens with IBD is to achieve deep remission before drug withdrawal to avoid relapse. In order to evaluate the healing of mucosa, it is currently necessary to carry out an endoscopy, despite the additional information provided by FC and blood samples. The endoscopic procedure is uncomfortable for the patient, time consuming and expensive. We therefore seek, on the basis of existing knowledge and using a correlation between FC, blood tests and clinical remission with endoscopic findings, to establish some non-invasive biomarkers that might express deep remission. In the long run, threshold levels will be used as indicators for performing an endoscopy and, hopefully, reduce the need for it to be performed. We will compare the results from children and adults because it is likely there exist differences in their respective FC levels.

Histopathologic remission: Biopsies of the intestinal tissue can be evaluated histopathologically and indicate the level of microscopic inflammation and can assess the acute and chronic inflammatory signs at the cellular level, e.g. altered glandular structure, crypt abscess and ulcerations. By using the Karl Geboes grading system, microscopic histopathological deep remission can be assessed. We will explore the endoscopic 'gold standard' by comparing endoscopic remission with histopathological remission.

Immunological remission: In general, tissue factors are linked to various immunological pathways belonging to the innate, adaptive and regulatory immune response, comprising a pro-inflammatory and an anti-inflammatory response. This includes molecules such as cytokines, chemokines, adhesion molecules and their corresponding cellular and soluble receptors. Tumor-necrosis-factor (TNF)-alpha and interleukin 17A is two of several molecules in the pro-inflammatory process that is strongly associated with the grade of inflammation in IBD (Florholmen and Fries 2011). Olsen et al. 2009 have reported that a normalization of mucosal TNF-alpha in most ulcerative colitis patients will represent an endoscopically healed mucosa.

In addition to clinical indexes, endoscopic and histological criteria, we also introduce a molecular based Immunological Remission. A working hypothesis is that immunological remission is a state of normalization of the pro-inflammatory and anti-inflammatory processes in mucosa. The concept of immunological remission and the potential clinical impact are still in the early phases of evaluation, and to obtain a practical application a non-invasive test, such as one based on a stool sample, must be developed. In the current project, immunological remission will be a part of this study, as endoscopic and histopathology remission, with correlation to FC, blood tests and clinical remission.

Eligibility criteria: Inclusion Criteria:

* Patients scheduled for endoscopy
* Age 0 - 67 years
* Intestinal infections ruled out by stool sample analysis for pathogenic bacteria, parasites and Clostridium difficile
* CMV ruled out
* Fluent in Danish

Exclusion Criteria:

* American Society of Anesthesiologists (ASA) score III or above
* Patients who are alcohol or drug abusers

Primary outcomes:
measure: Fecal Calprotectin (FC)and clinical score
timeFrame: Two FC test will be analysed up to 1 week before the endoscopy. SCCAI will be collected up to 1 week before endoscopy.
Secondary outcomes:
measure: Histopathological and Immunological inflammation score
timeFrame: up to 8 weeks after endoscopy
Other outcomes:
measure: Endoscopic-, Histopathological- and Immunological- intestinal inflammation in children with IBD
timeFrame: Up to 2 years after endoscopy
Locations:
city: Herlev
country: Denmark
facility: Katrine Carlsen
Study officials:
affiliation: Departmen of Gastroenterology, Herlev University Hospital
name: Katrine Carlsen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology, Herlev University Hospital
name: Pia Munkholm, Professor
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Vibeke Wewer, MD, Phd
role: STUDY_CHAIR
affiliation: Department of Pathology, Herlev University Hospital
name: Lene Riis, MD, PhD
role: STUDY_CHAIR
affiliation: Hvidovre University Hospital
name: Christian Jakobsen, MD, PhD
role: STUDY_CHAIR
References: