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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cortisol releasing hormone group | Active Comparator | HVs will start with CRH infusion. |
|
| Placebo (sodium choride) group | Placebo Comparator | HVs will start with NaCl 0.9% (placebo) infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Corticotropin-release hormone | Drug | intravenous CRH (100 µg) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 30 minutes after CRH/placebo |
| Measure | Description | Time Frame |
|---|---|---|
| The effect of CRH on duodenal eosinophilia | Duodenal eosinophils (H&E) will be counted per mm2 via stained duodenal biopsy sections. | 2 hours after CRH/placebo |
| The effect of CRH on duodenal mucosal permeability |
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Inclusion Criteria:
Exclusion Criteria:
Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol
Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial
Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
Presence of a history of gastrointestinal surgery other than appendectomy
Presence of organic or functional gastrointestinal disease
Presence of gastro-intestinal symptoms
Major psychiatric disorder such as major depression
Presence of any disease affecting the gastrointestinal tract or hepatobiliary system.
History of allergic reaction to CRH
BMI equal to 30 mg/kg² or higher.
Use of drugs included in this list:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| I-Hsuan Huang | Leuven | 3000 | Belgium |
The Trial will be conducted in compliance with the requirements of the EU General Data Protection Regulation 2016/679 (GDPR), the relevant Belgian laws implementing the GDPR including the Belgian Privacy Act of 30 July 2018 on the protection of privacy in relation to the processing of personal data. Any collection, processing and disclosure of personal data, such as participant health and medical information is subject to compliance with the aforementioned personal data protection laws.
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To assess the effect of the CRH on on duodenal mast cell count, eosinophil count, immune activation and mucosal permeability, gastric accommodation, gastric sensitivity to distension and gastric emptying time, an interventional study will be conducted in 20 healthy subjects. The study is designed as a double-blind randomized crossover study with at least 7 days between the different study days.
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| Corticotropin-release hormone | Drug | a bolus dose (CRH 100 µg or placebo) will be administered, followed by a continuous infusion (CRH 1 µg/kg/h or placebo) |
|
Duodenal mucosa permeability on duodenal biopsies using adapted mini-Ussing chambers
| 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. | 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. | 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. | 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 | Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection |