Objective: As we have to integrate information on genetics, immune cells and microbes, a panel of biomaterials (isolated from blood, stool and gastrointestinal mucosal biopsies) will be sampled. From these samples genomic, transcriptomic,…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Aims: The primary aim of the currently proposed research is to get a better
understanding of how functional genetic variants influence the immune system of
the gastrointestinal tract. To achieve this, we will apply a holistic approach
using both transcriptome and microbiome data in the background of the genetic
and phenotypic profile of each individual. To generate this information, we
have to profile different cell types from patients and controls that are known
to play a role in immune processes. We aim to study immune effector cells,
fibroblasts and epithelial cells to get a better understanding of the role of
these cells in inflammatory conditions. The datasets derived from cell-specific
transcriptomic analyses and the microbiome, genome and phenotype data will be
analyzed and integrated using bioinformatics to develop insights into disease
mechanisms.
Main study parameters/endpoints: We will perform sequence-based transcriptomics
(RNAseq) to obtain profiles of all transcripts and correlate this to the
microbiome composition, genetic, serological and phenotypic data. We will
determine presence and functionality of the epithelial cells in organoids by
(immuno)histochemical staining for enzyme activity, antimicrobial proteins and
mucus production. Results will be compared between cases and controls.
Secondary outcome
The secondary aim is to construct and implement a patient-specific predictive
instrument for severe disease course.
Background summary
Rationale: During the past few years, enormous progress has been made in IBD
research: a study published last year in Nature Genetics, in which our research
group participated, brought the number of known genetic risk loci for IBD to
200. However, these risk variants are only markers and if causal variants have
been identified it is still unknown what their effect is in the gut mucosa.
Study objective
Objective: As we have to integrate information on genetics, immune cells and
microbes, a panel of biomaterials (isolated from blood, stool and
gastrointestinal mucosal biopsies) will be sampled. From these samples genomic,
transcriptomic, serological, and microbiomic data will be generated and
analysed. We will generate organoids from these mucosal biopsies to study the
architecture of the epithelium in vitro. This will be complemented with
phenotypic data acquired by examination of the study subjects at the time of
presentation, questionnaires, and from medical records. For IBD patients we
already have extensive prospectively gained phenotypic data available
(Parelsnoer Cohort/ UR IBD).
Study design
Study design: This study will be a non-therapeutic study, observational study
involving human subjects and human body materials. Patients that are scheduled
for endoscopy at the Gastroenterology and Hepatology department of the UMCG
will be recruited. The data will be generated and analysed at both the
department of Gastroenterology and Hepatology and the department of Genetics of
the UMCG.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: Only scheduled patients having a clinical
indication for endoscopies will be included, so patients won*t be subject to
any additional endoscopies. The harvesting of routine biopsies during endoscopy
is associated with a negligible risk of complications. From literature we have
learned that taking up to 38 additional endoscopic biopsies will not increase
the risk of complications (Yao, von Rosenvinge, Groden, & Mannon, 2009). Two
sites will be studied: the small bowel and the colon, since these two sites
show different involvement in the subtypes of IBD and have different
morphologies (Baumgart & Sandborn, 2012; Carrasco et al., 2016; Ordás, Eckmann,
Talamini, Baumgart, & Sandborn, 2012). We take up to twelve biopsies per site,
per endoscopy, so that immune cells can be studied (eight biopsies required, T.
Raine, personal communication) and epithelial cells can be derived (four
biopsies required (personal experience of this research group)). Three extra
tubes of blood (22.5ml) will be collected from a peripheral venous catheter
that is already in place for routine care at time of their scheduled visit for
endoscopy. This blood will be used for DNA/RNA analysis of genetic variants and
genes associated with IBD. Additionally, the patient will be asked to produce a
stool sample which will be collected at home, for identification of the
microbiome of the gut. All contributors will be requested to fill in a
questionnaire. We believe that the proposed studies will greatly contribute to
our understanding of the pathogenesis of IBD and that results will help
improving both diagnostics and treatment of IBD patients. Eventually, we expect
that our results contribute developing a personalised approach in the treatment
of IBD.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
- Written informed consent
- >= 18- years old at time of signing informed consent
- Must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
- Must be able to adhere to the study visit schedule and other protocol requirements;At least one of the following;
- Patients suffering from CD or UC diagnosed by the treating physician according to established clinical, serological and pathological definitions, who are planned for routine diagnostic endoscopy.
- Patients with suspected IBS according the treating physician, who are planned for routine diagnostic endoscopy
- Patients planned for routine screening/follow-up endoscopy for colorectal carcinoma and or adenomatous polyps.
- Patients who are suffering from intestinal inflammatory disorders other than IBD (including but not limited to celiac disease or graft-versus-host-disease), who are planned for routine diagnostic endoscopy.
Exclusion criteria
- No informed consent obtained for this study
- Severe psychiatric or physical illness
- Not being able to understand Dutch language
- Pregnancy
- Patients on therapeutic anticoagulants and therefore not qualifying for routine endoscopic procedures according to current national guidelines
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 | NL58808.042.16 |