Effect of CRH on Duodenal Markers and Gastric Sensorimotor Function

NCT ID: NCT05071781

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-21
• Study Completion Date: 2022-12-19

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.

Conditions

GI Motility Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Cortisol releasing hormone group

HVs will start with CRH infusion.

Group Type: ACTIVE_COMPARATOR

Corticotropin-release hormone

Intervention Type: DRUG

intravenous CRH (100 µg)

Corticotropin-release hormone

Intervention Type: DRUG

a bolus dose (CRH 100 µg or placebo) will be administered, followed by a continuous infusion (CRH 1 µg/kg/h or placebo)

Placebo (sodium choride) group

HVs will start with NaCl 0.9% (placebo) infusion

Group Type: PLACEBO_COMPARATOR

Corticotropin-release hormone

Intervention Type: DRUG

intravenous CRH (100 µg)

Corticotropin-release hormone

Intervention Type: DRUG

a bolus dose (CRH 100 µg or placebo) will be administered, followed by a continuous infusion (CRH 1 µg/kg/h or placebo)

Interventions

Corticotropin-release hormone

intravenous CRH (100 µg)

Intervention Type: DRUG

Corticotropin-release hormone

a bolus dose (CRH 100 µg or placebo) will be administered, followed by a continuous infusion (CRH 1 µg/kg/h or placebo)

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

I-Hsuan Huang

Leuven, , Belgium

Countries

Belgium

Other Identifiers

S65020

Identifier Type: -

Identifier Source: org_study_id