To explore regions of brain and brainstem activation in healthy volunteers during abdominal pain or discomfort after chemical nociceptive stimulation of the duodenum with capsaicin. In the future, we aim to perform the same study in IBS-/FD-patients…
ID
Source
Brief title
Condition
- Gastrointestinal motility and defaecation conditions
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
(ASL-) Voxel-wise blood oxygenation level dependent (BOLD) signal activity in
the NTS.
Secondary outcome
* Voxel-wise blood oxygenation level dependent BOLD signal activity in the
Cingulate Cortex, Insula, Thalamus, Prefrontal Cortex, Primary and Secondary
Somatosensory Cortex, Amygdala, PAG
* Baseline Cerebral Blood Flow
* Visual Analogue Scores during capsaicin and placebo infusion into the duodenum
* Gastro-intestinal Symptom Scores, Depression and Anxiety symptom scores
(HADS, PHQ-9, GAD-7), personality trait (BIG-FIVE-Inventory), Traumata in early
life, quality of life scores (SF-36), current affect scores (PANAS-SF), current
pain scores (BPI-SF) and gastrointestinal symptom scores (GSRS-IBS+), visceral
sensitivity index (VSI)
Background summary
Brain imaging has shown abnormal brain activations in response to visceral
stimulation in patients with the Irritable Bowel Syndrome (IBS). To investigate
the possible role of the Nucleus of the Solitary Tract (NTS), the primary relay
station in the brainstem for vagal afferents, its activation in IBS and
functional dyspepsia patients will be evaluated. Prior to this, an exploratory
study in healthy volunteers will be conducted (described in this protocol).
This will be the first high magnetic field fMRI study evaluating the possible
role of NTS activation in visceral abdominal pain. Moreover, this will be the
first fMRI study using duodenal capsaicin infusion as a stimulus, which is more
physiological than mechano-stimulation.
Study objective
To explore regions of brain and brainstem activation in healthy volunteers
during abdominal pain or discomfort after chemical nociceptive stimulation of
the duodenum with capsaicin. In the future, we aim to perform the same study in
IBS-/FD-patients to assess differences in fMRI findings related to nociceptive
processing and to assess patient characteristics associated with these
differences.
Study design
An explorative 7T fMRI study
Intervention
Duodenal capsaicin and placebo (saline + small amount of ethanol) infusion via
a nasoduodenal tube.
Study burden and risks
Volunteers will not benefit from participating in this study. There are no
risks associated with the introduction of a naso-duodenal tube under
fluoroscopy control, the radiation exposure of fluoroscopy is minimal: 0.05mSv.
Capsaicin infusion may cause abdominal cramps, a burning sensation, abdominal
pain, nausea or heartburn but symptoms will subside rapidly after
discontinuation of the infusion. The nasoduodenal tube and infusion pump are
safe to use in the magnetic field and have been tested for this purpose
extensively. Ultra high magnetic field MRI is very safe and no adverse events
are anticipated when taking into account all contra-indications. Solely
*Certified Users* will operate the MRI according to approved guidelines and
protocol. Subjects will be screened for contraindications (metal implants etc.)
prior to inclusion and again on the day of scanning. Some participants may
experience mild vertigo, nausea or a metal taste when entering the MRI
environment. In extremely rare cases, a small burn may arise due to heating
caused by radiofrequency. All participants will be informed about any
unexpected medical findings (MRI findings). In case the subject does not wish
to be informed, he is not allowed to participate in this study. Completing
questionnaires is non-invasive. Subjects will be informed about the risks and
burdens of the measurements beforehand.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
* Of female sex;
* Based on medical history and previous examination, no gastrointestinal
complaints can be defined;
* Age between 18 and 65 years;
* BMI between 18 and 30 kg/m2;
* Women in fertile age (<55 years old) must use contraception or be
postmenopausal for at least two years;
* All subjects should be right-handed.
Exclusion criteria
* Presence of metallic prostheses, pacemakers, metal clips on blood vessels,
metal parts in the eye, an intrauterine device, metal braces, facial tattoos
(including permanent eye make-up) and/or other metal objects;
* History of major head trauma or head/brain surgery;
* History of claustrophobia;
* History of severe or chronic cardiovascular, respiratory, urogenital,
gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes,
nose, throat), dermatological/connective tissue, musculoskeletal,
metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy,
major surgery and/or laboratory assessments which might limit participation in
or completion of the study protocol;
* Use of medication, including vitamin and iron supplementation, except oral
contraceptives, within 14 days prior to start of the study;
* Major abdominal surgery interfering with gastrointestinal function
(uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and
other surgery upon judgment of the principle investigator);
* Pregnancy, lactation, wish to become pregnant;
* High alcohol consumption (>15 alcoholic consumptions per week);
* Using drugs of abuse;
* Self-admitted HIV-positive state;
* Known allergic reaction to capsaicin;
* High intake of spicy (capsaicin containing) food (meaning an estimated intake
of > than 1.5mg/day), due to possible desensitization of the capsaicin receptor
TRPV1 (see further below);
* Administration of investigational drugs or participation in any scientific
intervention study which may interfere with this study (to be decided by the
principle investigator), in the 180 days prior to the study;
* Any evidence of structural brain abnormalities examined by anatomical MRI
will lead to exclusion.
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 |
|---|---|
| ClinicalTrials.gov | NCT02551029 |
| CCMO | NL51770.068.15 |