The Effect of Chlorpromazine on Esophageal Sensitivity in Healthy Volunteers.

NCT03183310 | Unknown

• 1 other identifier: S60403
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The effect of chlorpromazine (Largactil) on esophageal sensitivity will be investigated in this study. Overnight fasted subjects will be asked to fill out 2 questionnaires to assess the emotional status before their onset of the stimulation tests. The multimodal stimulation probe will be positioned through the mouth in the distal esophagus. After the ingestion of the stimulation probe, 10mg of chlorpromazine or placebo (saline) will be slowly administered via intravenous injection. Hereafter the multimodal stimulation tests will be initiated. Esophageal sensitivity will be assessed by performing thermal, mechanical, electrical and chemical stimulation of the esophagus. The chlorpromazine condition will be compared with a placebo condition, this will be organised on 2 separate study visits in a randomised order.

Conditions

Esophageal Reflux

Outcome Measures

Primary Outcomes (4)

• Measurement of changes in esophageal sensitivity after administration of Chlorpromazine

  Investigation of the effect of chlorpromazine 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 chlorpromazine condition to see if dopamine antagonism affects sensitivity to increasing temperature.

  Change in temperature sensitivity between the 2 sessions with at least one week interval, duration of each session: approximately 3 hours. Actual time frame of the temperature stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after administration of Chlorpromazine

  Investigation of the effect of chlorpromazine 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 chlorpromazine condition to see if dopamine antagonism affects sensitivity to increasing balloon volume.

  Change in mechanical sensitivity between the 2 sessions with at least one week interval, duration of each session: approximately 3 hours. Time frame of the actual mechanical stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after administration of Chlorpromazine

  Investigation of the effect of chlorpromazine 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 chlorpromazine condition to see if dopamine antagonism affects sensitivity to increasing intensity of electrical pulses.

  Change in electrical sensitivity between the 2 sessions with at least one week interval, duration of each session: approximately 3 hours. Time frame actual electrical stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after administration of Chlorpromazine

  Investigation of the effect of chlorpromazine on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the volume of infused acid (volume in mL) of the stimulation tests between the placebo and chlorpromazine condition to see if dopamine antagonism affects sensitivity to acid infusion. Investigation of the effect of chlorpromazine 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 chlorpromazine condition to see if dopamine antagonism affects sensitivity to increasing intensity of electrical pulses.

  Change in chemical sensitivity between the 2 sessions with at least one week interval, duration of each session: approximately 3 hours. Time frame of the actual chemical stimulation: 30 minutes

Study Arms (2)

Chlorpromazine

ACTIVE COMPARATOR

Administration of an intravenous bolus injection of 10 mg Chlorpromazine to investigate the effect on esophageal sensitivity.

Drug: Chlorpromazine; Device: Multimodal stimulation probe

Placebo (Saline)

PLACEBO COMPARATOR

Administration of an intravenous bolus injection of saline (placebo) as the control condition of chlorpromazine in this cross-over study.

Device: Multimodal stimulation probe; Drug: Placebo - Concentrate

Interventions

Chlorpromazine DRUG

an intravenous bolus injection of Chlorpromazine will be administered . After an incubation period of 15 minutes esophageal sensitivity will be assessed by multimodal stimulation to evaluate the effect of dopamine antagonism on esophageal sensitivity

Chlorpromazine

Multimodal stimulation probe DEVICE

The multimodal esophageal probe allows to perform 4 types of stimulations in the esophagus (thermal, mechanical, electrical and chemical stimulation). These 4 modalities will be evaluated to assess esophageal sensitivity.

Chlorpromazine; Placebo (Saline)

Placebo - Concentrate DRUG

an intravenous bolus injection of saline (NaCl 0.9%) will be administered . After an incubation period of 15 minutes esophageal sensitivity will be assessed by multimodal stimulation.

Placebo (Saline)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 60 years old

You may not qualify if:

• history of psychiatric disease or a positive first degree psychiatric family history,
• pregnancy or lactation,
• concomitant administration of any centrally activating medication or medication affecting esophageal motility,
• significant co-morbidities (neuromuscular, 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
• During the last two weeks before the study, the volunteers should be free from medication, except for oral contraceptives.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

Targid, KU Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

Chlorpromazine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jan Tack, MD, PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan Tack, MD, PhD

CONTACT

003216377474; jan.tack@kuleuven.be

Charlotte Broers

CONTACT

003216379086; charlotte.broers@kuleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sessions will run in a double-blind randomized-controlled way. The order of placebo and chlorpromazine administration will be randomized by an online randomization tool (http://www.randomization.com/). The randomization scheme will be carried out by an experienced independent researcher or study nurse, this person will prepare and inject chlorpromazine or placebo. In this way, the investigator performing the actual study and data analysis will be blinded until termination of the study.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: a randomized, double-blind, placebo-controlled study

Study Record Dates

• First Submitted: May 31, 2017
• First Posted: June 12, 2017
• Study Start: July 1, 2017
• Primary Completion: October 31, 2017
• Study Completion: October 31, 2017
• Last Updated: June 12, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)