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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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.


Detailed Summary:

  1. INTRODUCTION Gastro-esophageal reflux disease (GERD), defined as the presence of symptoms or lesions that can be attributed to the reflux of gastric contents into the esophagus, is an increasingly prevalent condition in Western societies. The most typical symptoms are heartburn and regurgitation, but GERD can manifest itself through a variety of esophageal and extra-esophageal symptoms (e.g. chronic cough).

    In humans, pain is a multimodal experience composted of sensory, physiological and psychological aspects. In order to mimic the clinical situation, experimental models should be based on testing regimens in which different receptors and central nervous system mechanisms are activated.

    Advances in esophageal sensory stimulation have established that both typical and atypical symptoms may not only arise from acid reflux, but also from reflux events with less acidic pH (pH 4-7). In GERD patients with symptoms that persist in spite of acid suppressive therapy, ongoing weakly-acidic and non-acid reflux is now well established as the main underlying factor.

    The basis for symptom generation during weakly-acidic reflux events remains to be determined, but acid sensitivity in the pH range 4-7, mechanical distention (enhanced by air in the refluxate), sensitivity to other chemical factors (e.g. bile) and esophageal hypersensitivity to physiological levels of reflux have all been proposed.

    The investigators speculate that visceral hypersensitivity plays an important role in symptom perception. This is suggested by the reflux parameters that are usual within the physiological number during proton pump inhibitor (PPI) therapy. Also, our group previously dem
    Sponsor: Prof Dr Jan Tack

    Current Primary Outcome: Changes in esophageal contractile properties after Intravenous CRH administration in Healthy Volunteers [ Time Frame: approximately 2 hours study period, effect of CRH will be evaluated 30 minutes after the administration ]

    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.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: Universitaire Ziekenhuizen Leuven

    Dates:
    Date Received: December 10, 2015
    Date Started: October 2014
    Date Completion:
    Last Updated: April 6, 2016
    Last Verified: April 2016