Effect of CRH on Duodenal Markers and Gastric Sensorimotor Function

Phase 4

Completed

• Conditions: GI Motility Disorder
• Interventions: Drug: Corticotropin-release hormone

• Registration Number: NCT05071781
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-05-21
• Study First Submitted: 2021-08-16
• Study First Submitted QC: 2021-10-07
• Study First Posted: 2021-10-08
• Primary Completion: 2022-12-19
• Study Completion: 2022-12-19
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-01
• Last Update Posted: 2024-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Voluntary written informed consent of the participant has been obtained prior to any screening procedures
2. Women of child-bearing potential agree to apply a highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or postmenopausal with at least 2 year without spontaneous menses.
3. Healthy volunteers
4. Subjects aged 18-55 years old (55y included).
5. Male or female subjects.
6. Subjects who are capable to understand the study and the questionnaires, and to comply with the study requirements.

Exclusion Criteria

1. Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol

2. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial

3. 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

4. Presence of a history of gastrointestinal surgery other than appendectomy

5. Presence of organic or functional gastrointestinal disease

6. Presence of gastro-intestinal symptoms

7. Major psychiatric disorder such as major depression

8. Presence of any disease affecting the gastrointestinal tract or hepatobiliary system.

9. History of allergic reaction to CRH

10. BMI equal to 30 mg/kg² or higher.

11. Use of drugs included in this list:

    1. Opioids (unless short intake for acute pain and > 1month ago)
    2. Amitriptyline or mirtazapine; other antidepressants are allowed if the HV is on a stable dose and the drug is not combined with other antidepressants.
    3. Corticosteroids
    4. Antihistaminic drugs (last 2 weeks)
    5. Proton pump inhibitors (last 2 weeks)
    6. Disodiumchromoglycate or other mast cell stabilizers (last 2 weeks)
    7. Leukotriene receptor antagonists (last 2 weeks)
    8. NSAIDs (last 2 weeks)
    9. Antibiotics (last 2 months)
    10. Probiotics (last 2 weeks)
    11. Other medication: to be discussed with physician

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cortisol releasing hormone group	Corticotropin-release hormone	HVs will start with CRH infusion.
Placebo (sodium choride) group	Corticotropin-release hormone	HVs will start with NaCl 0.9% (placebo) infusion

Primary Outcome Measures

Name	Time	Method
The effect of CRH on sensitivity to gastric distention (part 2)	30 minutes after CRH/placebo	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.
The effect of corticotrophin release hormone (CRH) on duodenal mast cell count	2 hours after CRH/placebo	Duodenal mast cells (c-kit) will be counted per mm2 via stained duodenal biopsy sections.

Secondary Outcome Measures

Name	Time	Method
The effect of CRH on gastroduodenal symptoms.	Every 15 minutes during CRH/placebo infusion for 4 hours	Assessments using Visual Analog Score for GI symptoms which including pain, nausea, bloating, vomiting.
The effect of CRH on duodenal eosinophilia	2 hours after CRH/placebo	Duodenal eosinophils (H\&E) will be counted per mm2 via stained duodenal biopsy sections.
The effect of CRH on duodenal mucosal permeability	2 hours after CRH/placebo	Duodenal mucosa permeability on duodenal biopsies using adapted mini-Ussing chambers
The effect of CRH on gastric emptying time	30 minutes after CRH/placebo	Gastric emptying time in minutes t (1/2) will be measured by 13C-octanoic acid breath test.
The effect of CRH on gastric accommodation	30 minutes after CRH/placebo	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.
The effect of CRH on salivary cortisol level	Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection	Salivary cortisol level in nmol/L during placebo or CRH infusion

Trial Locations

Locations (1)

I-Hsuan Huang; 🇧🇪 Leuven, Belgium