The Effect of Corticotrophin-releasing Hormone (CRH) on Esophageal Sensitivity in Healthy Volunteers
Status:
Completed
Trial end date:
2014-05-01
Target enrollment:
Participant gender:
Summary
Introduction and aim
Stress is well known to affect visceral sensitivity in Human. The investigators speculate
that visceral hypersensitivity plays an important role in symptom perception in
gastro-esophageal reflux disease (GERD). The role of acute stress mimicked by corticotrophin
releasing hormone (CRH) administration on esophageal sensitivity has not been studied. The
investigators hypothesize that stress mediated through CRH-release increases esophageal
sensitivity. A first step in the investigation of this hypothesis is to study whether
administration of CRH has an influence on esophageal sensitivity in healthy volunteers (HV).
Therefore, the aim of this study is to investigate the effect of CRH-administration on
esophageal sensitivity in a group of HV.
Methods
The study will be performed in cross-over on 15 HV with no prior history of digestive
disease. Esophageal sensitivity will be tested by multimodal stimulation on two sessions
(placebo and CRH-administration), with an interval at least of one week. The two sessions
will be scheduled by randomization for every subject. After blinded administration of CRH
100µg or placebo IV, esophageal sensitivity will be assessed using a multimodal esophageal
stimulation probe which allows thermal, mechanical, electrical and chemical stimulations of
the esophagus. Esophageal sensitivity will be assessed using Visual Analogue Scale (VAS), the
mood with specific questionnaires (Manikin Self assessment SAM, Profile of Mood Schedule
(POMS, State Trait Anxiety Inventory (STAI)) and the cortisol with salivary samples.
Statistical analysis
Esophageal sensitivity for the different stimuli (heat, mechanical, electrical and chemical)
will be compared between CRH and placebo conditions. To determine the stress-inducing
capability of CRH-administration, the POMS questionnaire, STAI, Manikin self assessment and
cortisol levels after the stress-protocol will be compared with the basal measurements.
Perspectives
If CRH-administration increases esophageal sensitivity, a stress model could be applied to
investigate the influence of a real life stressor on esophageal sensitivity in healthy
subjects. In a third part, a mast-cell stabilizing drug could be tested after administration
of a stressor in order to investigate its role on esophageal sensitivity. In the future, this
might be proposed to refractory GERD in a controlled randomized trial.