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

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Universitaire Ziekenhuizen Leuven
• Treatments: Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Hormones

Criteria

Inclusion Criteria:

• healthy volunteers

• age between 18 to 60 years

Exclusion Criteria:

• no history of gastrointestinal symptoms or complaints

• history of allergic reaction to CRH

• 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, ENT or gastric surgery or endoscopic anti-reflux procedure

• history of gastrointestinal disease and first degree relatives with Crohn's disease or celiac disease