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Completed

NCT Number: NCT05071781

Effect of CRH on Duodenal Markers and Gastric Sensorimotor Function

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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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

I-Hsuan Huang

Leuven, 3000, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Voluntary written informed consent of the participant has been obtained prior to any screening procedures
  • 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.
  • Healthy volunteers
  • Subjects aged 18-55 years old (55y included).
  • Male or female subjects.
  • Subjects who are capable to understand the study and the questionnaires, and to comply with the study requirements.

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

Treatment and study plan

Corticotropin-release hormone

Drug

intravenous CRH (100 µg)

Primary outcomes

  1. The effect of corticotrophin release hormone (CRH) on duodenal mast cell count

    Time frame: 2 hours after CRH/placebo

    Duodenal mast cells (c-kit) will be counted per mm2 via stained duodenal biopsy sections.

  2. The effect of CRH on sensitivity to gastric distention (part 2)

    Time frame: 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.

Secondary outcomes

  1. The effect of CRH on duodenal eosinophilia

    Time frame: 2 hours after CRH/placebo

    Duodenal eosinophils (H&E) will be counted per mm2 via stained duodenal biopsy sections.

  2. The effect of CRH on duodenal mucosal permeability

    Time frame: 2 hours after CRH/placebo

    Duodenal mucosa permeability on duodenal biopsies using adapted mini-Ussing chambers

  3. The effect of CRH on gastric emptying time

    Time frame: 30 minutes after CRH/placebo

    Gastric emptying time in minutes t (1/2) will be measured by 13C-octanoic acid breath test.

  4. The effect of CRH on gastric accommodation

    Time frame: 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.

  5. The effect of CRH on gastroduodenal symptoms.

    Time frame: Every 15 minutes during CRH/placebo infusion for 4 hours

    Assessments using Visual Analog Score for GI symptoms which including pain, nausea, bloating, vomiting.

  6. The effect of CRH on salivary cortisol level

    Time frame: Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection

    Salivary cortisol level in nmol/L during placebo or CRH infusion

Sponsors and collaborators

Lead sponsor

Universitaire Ziekenhuizen KU Leuven

Other

Registry information

Official study title

The Effect of Corticotropin Release Hormone on Duodenal Markers and Gastric Sensorimotor Function in Healthy Volunteers

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Oct 8, 2021
Registry last updated
Jul 3, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.