Clinical trial NCT05071781: Effect of CRH on Duodenal Markers and Gastric Sensorimotor Function
Official title: The Effect of Corticotropin Release Hormone on Duodenal Markers and Gastric Sensorimotor Function in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: GI Motility Disorder
Keywords: cortisol releasing hormone
3.1 Functional dyspepsia
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2021-10-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: The effect of corticotrophin release hormone (CRH) on duodenal mast cell count
timeFrame: 2 hours after CRH/placebo
measure: The effect of CRH on sensitivity to gastric distention (part 2)
timeFrame: 30 minutes after CRH/placebo
Secondary outcomes:
measure: The effect of CRH on duodenal eosinophilia
timeFrame: 2 hours after CRH/placebo
measure: The effect of CRH on duodenal mucosal permeability
timeFrame: 2 hours after CRH/placebo
measure: The effect of CRH on gastric emptying time
timeFrame: 30 minutes after CRH/placebo
measure: The effect of CRH on gastric accommodation
timeFrame: 30 minutes after CRH/placebo
measure: The effect of CRH on gastroduodenal symptoms.
timeFrame: Every 15 minutes during CRH/placebo infusion for 4 hours
measure: The effect of CRH on salivary cortisol level
timeFrame: Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: I-Hsuan Huang
Study officials:
References: