The Effect of Corticotrophin-releasing Hormone (CRH) on Esophageal Motility in Healthy Volunteers

NCT02736734 | Completed Phase 4

• 1 other identifier: S57111
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Stress is well known to affect visceral sensitivity and gastrointestinal function in general. A majority of patients with gastroesophageal reflux disease (GERD) report stress as an important factor triggering symptom exacerbation. A real-life stressor could exacerbate heartburn symptoms in GERD patients by enhancing perceptual response to esophageal acid exposure. In Irritable Bowel Syndrome (IBS) patients, visceral hypersensitivity is a major pathophysiological mechanism and stress is shown to trigger or exacerbate symptoms. A possible mechanism of stress-induced visceral sensitivity could be the barrier dysfunction. Indeed, in a study performed by our group, in human, an acute psychological stressor induces hyperpermeability in a mast cell dependent fashion and exogenous peripheral corticotrophin-releasing hormone (CRH) recapitulated its effects on barrier function. This increase in intestinal permeability is a phenomenon which appears as a prerequisite for visceral hypersensitivity. Furthermore, few studies indicate that human intestinal motility is probably modulated by CRH. It has been shown that the brain-gut axis in IBS patients has an exaggerated response to CRH.To our knowledge, the acute effect of exogenous CRH on esophageal motility has not been studied before.

Conditions

Esophageal Motility Disorders

Outcome Measures

Primary Outcomes (1)

• Changes in esophageal contractile properties after Intravenous CRH administration in Healthy Volunteers

  The investigators will evaluate if the administration of intravenous CRH alters esophageal contractile properties. Esophageal contractile properties are measured by high resolution manometry (HRM). HRM measurements in the esophagus will be performed before and after CRH administration. The investigators will compare 3 HRM parameters (distal contractile integral (mmHg.s.cm), intrabolus pressure (mmHg), LES relaxation (mmHg)) before and after the administration of CRH and assess the number of HV in which these 3 parameters are altered after CRH administration to be able to report changes in contractile properties of the esophagus.

  approximately 2 hours study period, effect of CRH will be evaluated 30 minutes after the administration

Study Arms (1)

CRH condition

OTHER

All HV first underwent a baseline manometry measurement. After 30 minutes, an intravenous CRH injection was done. The same measurement was repeated but now with CRH administered.

Drug: CRH

Interventions

CRH DRUG

CRH injection: 100 µg CRH powder for injection (CRH Ferring) dissolved in 1ml NaCl 0.9%, administration intravenously over the course of 1 minute to avoid side effects.

Also known as: CRH, Ferring

CRH condition

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• No history of gastrointestinal symptoms or complaints.

You may not qualify if:

• History of allergic reaction to CRH, atopy (eczema, asthma, food allergies, allergic rhinoconjunctivitis) or multiple allergies to several drugs
• Pregnancy or lactation
• Concomitant administration of monoamine oxidase inhibitors (MAOI), verapamil or diltiazem or medication affecting esophageal motility
• Significant co-morbidities (neuromuscular, psychiatric, cardiovascular, pulmonary, endocrine, autoimmune, renal and hepatic)
• Prior history of esophageal, Ear Nose and Throat, or gastric surgery or endoscopic anti-reflux procedure
• History of gastrointestinal disease and first degree relatives with Crohn's disease or celiac disease.
• During the last two weeks before the study the volunteers should be free from medication, except for oral contraceptives

Sponsors & Collaborators

• Prof Dr Jan Tack: lead

Study Sites (1)

Targid, KU Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

MeSH Terms

Conditions

Esophageal Motility Disorders

Interventions

Corticotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Jan F Tack, MD, PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr., MD, PhD

Study Record Dates

• First Submitted: December 10, 2015
• First Posted: April 13, 2016
• Study Start: October 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 13, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)