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Effect of CRH on Duodenal Markers and Gastric Sensorimotor Function

7. oktober 2021 oppdatert av: Universitaire Ziekenhuizen KU Leuven

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

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.

Studieoversikt

Studietype

Intervensjonell

Registrering (Forventet)

20

Fase

  • Fase 4

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 55 år (Voksen)

Tar imot friske frivillige

Ja

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: Randomisert
  • Intervensjonsmodell: Crossover-oppdrag
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Aktiv komparator: Cortisol releasing hormone group
HVs will start with CRH infusion.
intravenous CRH (100 µg)
a bolus dose (CRH 100 µg or placebo) will be administered, followed by a continuous infusion (CRH 1 µg/kg/h or placebo)
Placebo komparator: Placebo (sodium choride) group
HVs will start with NaCl 0.9% (placebo) infusion
intravenous CRH (100 µg)
a bolus dose (CRH 100 µg or placebo) will be administered, followed by a continuous infusion (CRH 1 µg/kg/h or placebo)

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
The effect of corticotrophin release hormone (CRH) on duodenal mast cell count
Tidsramme: 2 hours after CRH/placebo
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)
Tidsramme: 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.
30 minutes after CRH/placebo

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
The effect of CRH on duodenal eosinophilia
Tidsramme: 2 hours after CRH/placebo
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
Tidsramme: 2 hours after CRH/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
Tidsramme: 30 minutes after CRH/placebo
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
Tidsramme: 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.
30 minutes after CRH/placebo
The effect of CRH on gastroduodenal symptoms.
Tidsramme: Every 15 minutes during CRH/placebo infusion for 4 hours
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
Tidsramme: Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection
Salivary cortisol level in nmol/L during placebo or CRH infusion
Right before CRH/placebo injection, 15, 30, 60, 120 minutes after injection

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

21. mai 2021

Primær fullføring (Forventet)

1. juni 2022

Studiet fullført (Forventet)

1. juli 2022

Datoer for studieregistrering

Først innsendt

16. august 2021

Først innsendt som oppfylte QC-kriteriene

7. oktober 2021

Først lagt ut (Faktiske)

8. oktober 2021

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

8. oktober 2021

Siste oppdatering sendt inn som oppfylte QC-kriteriene

7. oktober 2021

Sist bekreftet

1. oktober 2021

Mer informasjon

Begreper knyttet til denne studien

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

IPD-planbeskrivelse

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.

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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