In the present study, during Part 1, after a baseline gastroduodenoscopy, the investigators will perform a gastroduodenoscopy twice, to take duodenal biopsies before and 2 hours after administration of CRH/placebo. The investigators will measure mucosal integrity and markers of immune activation as outlined in Parts A and B, and will use transmission electron microscopy to evaluate mast cell and eosinophil degranulation. After an interval period of at least 1 week, CRH or placebo will be administrated again in a crossover fashion. As a complementary study, the investigators will also test the effect of ex vivo mast cell blockade by lodoxamide to evaluate whether mast cells are involved in the hypothesized effect of CRH on duodenal permeability. In a second part of this study, Part 2, the investigators will perform a gastric barostat, to measure the gastric accommodation and sensitivity to distension, and a carbon-13-octanoic acid breath test to measure the gastric emptying time after administration of CRH/placebo. Healthy volunteers will have the option to choose to which part of the study (part 1 or 2) they wish to participate. They can also choose to cooperate to both study parts if preferred.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
20
intravenous CRH (100 µg)
a bolus dose (CRH 100 µg or placebo) will be administered, followed by a continuous infusion (CRH 1 µg/kg/h or placebo)
I-Hsuan Huang
Leuven, Belgium
The effect of corticotrophin release hormone (CRH) on duodenal mast cell count
Duodenal mast cells (c-kit) will be counted per mm2 via stained duodenal biopsy sections.
Time frame: 2 hours after CRH/placebo
The effect of CRH on sensitivity to gastric distention (part 2)
Visceral sensitivity will be measured by barostat. Discomfort threshold will be defined as the first level of pressure and the corresponding volume that provokes discomfort. Pressure thresholds will be expressed both as pressures relative to minimal distending pressure and as absolute pressures.
Time frame: 30 minutes after CRH/placebo
The effect of CRH on duodenal eosinophilia
Duodenal eosinophils (H\&E) will be counted per mm2 via stained duodenal biopsy sections.
Time frame: 2 hours after CRH/placebo
The effect of CRH on duodenal mucosal permeability
Duodenal mucosa permeability on duodenal biopsies using adapted mini-Ussing chambers
Time frame: 2 hours after CRH/placebo
The effect of CRH on gastric emptying time
Gastric emptying time in minutes t (1/2) will be measured by 13C-octanoic acid breath test.
Time frame: 30 minutes after CRH/placebo
The effect of CRH on gastric accommodation
Gastric accommodation will be measured by barostat. Accommodation to a meal will be expressed as the average increase in intragastric volume during the first 4 postprandial hours.
Time frame: 30 minutes after CRH/placebo
The effect of CRH on gastroduodenal symptoms.
Assessments using Visual Analog Score for GI symptoms which including pain, nausea, bloating, vomiting.
Time frame: Every 15 minutes during CRH/placebo infusion for 4 hours
The effect of CRH on salivary cortisol level
Salivary cortisol level in nmol/L during placebo or CRH infusion
Time frame: Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection
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