To gain insight in the disease mechanisms of IBD, the immune system, gut and oral microbiome, environmental factors, the intestinal mucus barrier, intestinal epithelium, nutritional factors and metabolome will be studied in unaffected siblings of…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Comparisons will be made between siblings of twin pairs and between IBD
patients and non-IBD controls. Amongst others, changes in immune parameters in
the mucosal and peripheral blood compartment, gut and oral microbiome,
epithelium and mucus barrier function, and the metabolome will be studied. In
addition, correlations between demographic, environmental and nutritional
factors will be made, and quality of life an symptom fluctuations prior to or
during IBD will be studied.
Secondary outcome
See above.
Background summary
Inflammatory Bowel Diseases (IBD), i.e. Crohn*s Disease (CD) and Ulcerative
Colitis (UC), are thought to arise in genetically susceptible individuals in
the context of environmental triggers, with a potential dominant role for the
interplay between the gut microbiota, and the mucosal immune system. However,
the relative importance and the exact role of these factors in the pathogenesis
of IBD is presently unknown. Interpretation of published research in this field
is often hampered by reverse causation, and data generated in animal models
cannot be directly extrapolated to the human condition. The disease is probably
triggered years before the occurrence of symptoms, but currently patients are
only identified when clinical disease is established. The preclinical status of
IBD might hold the key to understanding the pathogenesis of IBD and could
provide a huge window of opportunity of halting or even preventing disease
development. At this time, data on this phase of the disease are virtually
non-existent. What we do know is that unaffected siblings of an IBD affected
individual are at increased risk of developing IBD. Therefore, studying IBD
discordant twins gives the unique opportunity to 1) define mechanisms that
underlie the early development of IBD and 2) identify markers of preclinical
IBD.
Study objective
To gain insight in the disease mechanisms of IBD, the immune system, gut and
oral microbiome, environmental factors, the intestinal mucus barrier,
intestinal epithelium, nutritional factors and metabolome will be studied in
unaffected siblings of IBD-affected individuals with a high risk of developing
IBD compared with the IBD-affected twin individual, IBD-affected twin pairs,
and healthy twin pairs.
Study design
Observational study with both a cross-sectional and longitudinal design. All
participants will participate in the cross-sectional part, and a selection of
participants will be followed over time.
Study burden and risks
At baseline, demographic factors and disease characteristics will be collected
for all participants. The following parameters and biomaterials will be
collected if specific informed consent is obtained: nutritional questionnaire
data, environmental data, 60mL blood, faecal samples, pharyngeal swabs, urine
samples, and rectal biopsies. If a patient agrees, the following will be
collected around a colonoscopy for regular care: ileum, colon and rectal
biopsies, as well as questionnaire data, blood, faecal, pharyngeal swabs and
urine samples. A subgroup of participants will be followed-up at intervals of 6
months or one year for longitudinal studies. In these, the same parameters and
biomaterials as at baseline will be collected. Rectal biopsies will be obtained
only at yearly follow-up visits. If a participant consents and he/she still
posesses deciduous teeth that they had changed in their childhood, we will also
collect these deciduous teeth.
Due to the observational design of the study participants will not have direct
benefit from participation. However insights gained from this cohort will
increase our understanding from IBD, which can lead to improvement of care for
IBD on the long-term. The blood withdrawal, urine sampling, pharyngeal swabs,
and faecal sampling do not pose risks to participants. Biopsy taking carries a
very low risk of bleeding or perforation of approximately 1 per 1000
colonoscopies. As we are performing only proctoscopies, we expect the risks of
perforation and bleeding to be negligible. Furthermore, bowel preparation is
not mandatory, rendering the procedure less burdensome for the participant.
The risks of data and biomaterial collection during a colonoscopy for regular
care do not increase risks that are already present because of the planned
colonoscopy.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria for the IBD-discordant and IBD-concordant twins or multiples:
- Born as a sibling of, either a monozygous or dizygous, twin pair or multiplex
- One or more twin-siblings or multiples are affected with IBD, i.e. CD, UC or
IBD unspecified (self-reported diagnosis, to be confirmed during the study by
clinical, endoscopic or histological reports from the treating physician)
- Age: 16 years and older, In order to be eligible to participate in this
study, a subject must meet all of the following criteria for the unaffected
controls (preferably twins or multiples):
- None of the siblings of the twin are affected with IBD, i.e. CD, UC or IBD
unspecified
- Age: 16 years and older
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- No consent to participate in the study.
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 | NL61114.041.17 |