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

NCT02674256 | Completed Phase 4

• 1 other identifier: S56177
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Sensitivity (Hyper); Gastrointestinal

Keywords

health; age between 18 to 60 years old; no history of gastrointestinal symptoms or complaints

Outcome Measures

Primary Outcomes (4)

• Measurement of changes in esophageal sensitivity after IV CRH administration

  Investigation of the effect of CRH-administration on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the Temperature values (°C) of the stimulation tests between the placebo and CRH condition to see if CRH affects the sensitivity to increasing temperature.

  2 sessions per HV with at least one week interval, duration of each session: approximately 2 hours and 30 minutes. Temperature stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after IV CRH administration

  Investigation of the effect of CRH-administration on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the balloon volumes (volume in ml) of the stimulation tests between the placebo and CRH condition to see if CRH affects the sensitivity to increasing balloon volume.

  2 sessions per HV with at least one week interval, duration of each session: approximately 2 hours and 30 minutes. Mechanical stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after IV CRH administration

  Investigation of the effect of CRH-administration on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the tolerated intensity of the electrical pulses (mA) of the stimulation tests between the placebo and CRH condition to see if CRH affects the sensitivity to increasing electrical pulses.

  2 sessions per HV with at least one week interval, duration of each session: approximately 2 hours and 30 minutes. Electrical stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after IV CRH administration

  Investigation of the effect of CRH-administration on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the volume of infused acid (ml) of the stimulation tests between the placebo and CRH condition to see if CRH affects the sensitivity to acid infusion.

  2 sessions per HV with at least one week interval, duration of each session: approximately 2 hours and 30 minutes. Chemical stimulation: 30 minutes

Study Arms (2)

CRH injection

ACTIVE COMPARATOR

Intervention: intravenous injection of CRH 100µg CRH powder for injection (CRH ferring®, Ferring, Aalst, Belgium) and 1 mL of NaCl 0.9% will be put together then the solution will be injected IV over the course of 1 minute

Drug: CRH

placebo injection

PLACEBO COMPARATOR

Intervention: intravenous saline injection 1mL of saline will be injected intravenously over the course of 1 minute

Other: Placebo

Interventions

CRH DRUG

100µg CRH powder for injection (CRH ferring®, Ferring, Aalst, Belgium) and 1 mL of NaCl 0.9% will be put together, then the solution will be injected intravenously over the course of 1 minute

Also known as: CRH ferring®, Ferring, Aalst, Belgium

CRH injection

Placebo OTHER

1 mL of NaCl 0.9% will be injected intravenously over the course of one minute

Also known as: Saline solution

placebo injection

Eligibility Criteria

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

You may qualify if:

• healthy volunteers
• age between 18 to 60 years

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

MeSH Terms

Conditions

Hypersensitivity

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jan F Tack, MD, PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Dr

Study Record Dates

• First Submitted: March 25, 2014
• First Posted: February 4, 2016
• Study Start: March 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: February 4, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will not share