The primary objective of the present study is to assess the involvement of the duodenal TRPV-1 neuropeptide pathway in symptom perception in FD patients compared to healthy controls. The present study has several secondary objectives with regard to…
ID
Source
Brief title
Condition
- Gastrointestinal conditions NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of the present study is to assess the involvement of the
duodenal TRPV-1 neuropeptide pathway in symptom perception in FD patients
compared to healthy controls.
Secondary outcome
Symptoms:
- To assess whether there are differences in gastrointestinal symptoms,
psychological symptoms and quality of life between FD patients and healthy
controls by using retrospective questionnaires.
- To evaluate the number of FD patients with comorbid diagnosis of IBS.
Gastric and duodenal tissue:
- To assess the difference in transcription of genes encoding for proteins
involved in intestinal barrier function (e.g. tight junction proteins) and
symptom perception (e.g. TRPV-1), as well as protein expression of these
proteins in both stomach and duodenum between FD patients and healthy controls.
- To compare serotonin metabolism in mucosal tissue (e.g. 5-HT, 5-HIAA) between
FD patients and healthy controls.
Predominant symptoms
- To assess whether there are differences in parameters involved in the TRPV-1
neuropeptide pathway (e.g. TRPV-1 mRNA transcription, neuropeptide
concentrations) between (1) patients with predominant pain symptoms and (2)
patients with predominant symptoms of epigastric fullness and bloating.
Background summary
Functional dyspepsia is a common gastrointestinal disorder with a negative
impact on daily functioning and quality of life. The pathophysiology of FD
remains largely unknown, although a multifactorial pathophysiology is
suggested. Previous investigations found evidence for both mechanical and
chemical visceral hypersensitivity in FD patients compared to healthy controls.
Patients with FD demonstrate chemical hypersensitivity to capsaicin ingestion
compared to healthy controls. Capsaicin is a chemical agonist of TRPV-1
receptors which are present on afferent sensory nerves in the gastrointestinal
mucosa. Activation of TRPV-1 sensitive neurons leads to release of
neuropeptides including substance P and somatostatin. It is suggested that
activation of this TRPV-1 neuropeptide pathway is involved in symptom
perception in FD patients. Moreover, several publications found evidence for
involvement of the duodenum in the pathophysiology of functional dyspepsia with
an impaired duodenal permeability in FD patients compared to healthy controls.
The primary focus of the present study is the duodenal TRPV-1 neuropeptide
pathway. However, serotonin is another important neurotransmitter involved in
local processes in the gastrointestinal tract (e.g. secretion, motility) as
well as in pain perception. Up till now, studies evaluating serotonin
metabolism in FD patients are limited with one study describing a decreased
plasma serotonin level in FD patients compared to healthy controls. Information
about serotonin metabolism in gastrointestinal mucosa is lacking.
Study objective
The primary objective of the present study is to assess the involvement of the
duodenal TRPV-1 neuropeptide pathway in symptom perception in FD patients
compared to healthy controls. The present study has several secondary
objectives with regard to intestinal permeability and serotonin metabolism.
Study design
The study design conforms to a case-control study with inclusion of both FD
patients and healthy controls. All participants will undergo an upper
gastrointestinal endoscopy with biopsy taking from stomach and duodenum.
Symptoms will be assessed using retrospective questionnaires.
Study burden and risks
Healthy controls and FD patients will undergo an upper gastrointestinal
endoscopy with multiple biopsy taking from stomach and duodenum. Endoscopy will
be performed by experienced gastroenterologists and this is a standard
diagnostic procedure that takes about 20 minutes. A diagnostic endoscopy is a
safe procedure and one large investigation in the USA described an overall
complication rate of 0.13% and associated mortality of 0.004%. The most
important complications are perforations and significant hemorrhages, which,
however are rarely seen (0.0009% and 0.002%, respectively). A recent
publication evaluated the safety of multiple biopsy taking during endoscopic
procedures (with a mean of 35 biopsies per procedure) for research purposes and
they found no association between the number of biopsies taken and the
occurrence of complications. After endoscopy, side effects are not often
reported. Participants can complain about a sore throat or bloated feeling,
which usually disappear short after the endoscopy. FD patients participating in
the present study have all a medical indication for upper endoscopy and they
receive this investigation as part of regular patient care. For study purposes,
(additional) biopsies will be taken.
Assessment of symptoms with retrospective questionnaires is safe and no
problems are expected.
In case of unexpected findings during endoscopy of healthy controls, these will
be reported to the participant and to his/her general practitioner. As FD
patients will undergo endoscopy as part of regular care to exclude organic
diseases, the referring physician (general practitioner and/or specialist) will
be informed about the findings during endoscopy.
P. Debyelaan 25
Maastricht 6229 HX
NL
P. Debyelaan 25
Maastricht 6229 HX
NL
Listed location countries
Age
Inclusion criteria
Healthy controls <= No gastrointestinal symptoms or history of gastrointestinal
disease, especially not meeting criteria for functional dyspepsia and IBS
(according to the ROME III criteria), Functional dyspepsia patients <= Patients
referred for upper gastrointestinal endoscopy by either general practitioners
or doctors from the gastroenterology outpatient clinic, meeting ROME III
criteria for functional dyspepsia
Exclusion criteria
Healthy volunteers and functional dyspepsia patients:
1. Inability to stop the intake of NSAIDs within 14 days prior to endoscopy.
2. Inability to stop the intake of medication affecting gastrointestinal
function (e.g. proton pump inhibitors, prokinetics, laxatives) within 5 days
prior to endoscopy
3. Current use of antidepressants
4. Medical history of diabetes mellitus
5. Medical history of coeliac disease
6. Organic disease at upper gastrointestinal endoscopy (i.e. erosive
esophagitis, Barrett*s esophagus, benign esophageal stricture, Schatzki ring,
esophageal carcinoma, esophageal candidiasis, gastric ulcer, gastric erosions,
gastric cancer, duodenal erosions or duodenal ulcer).
7. First-degree family members with diabetes mellitus type I, coeliac disease,
Crohn*s disease or ulcerative colitis
8. Medical history of food allergy or anamnestic evidence of food allergy
9. Presence of coagulation disorders or use of anticoagulants
10. Dieting
11. Pregnancy or lactation
12. Smoking
13. Excessive alcohol use (>20 alcoholic consumptions/week) and inability to
avoid use of alcohol in the 2 days prior to endoscopy
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 | NL51112.068.14 |