The Effect of Naloxone and Methylnaltrexone on Esophageal Sensitivity in Health

NCT03014843 | Completed

• 1 other identifier: S54661
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this study was to investigate the effect of naloxone (IV or IM administration) and methylnaltrexone (subcutaneous administration) on esophageal sensitivity, in a group of healthy volunteers in order to evaluate the role of endogenous opiods in symptom perception in gastro-esophageal reflux disease. Esophageal sensitivity was assessed by using a multimodal esophageal stimulation protocol where sensitivity to thermal, mechanical, electrical and chemical stimulation was tested.

Conditions

Endogenous and Esophageal Sensitivity

Keywords

Esophagal sensitivity, GERD, endogenous opiods

Outcome Measures

Primary Outcomes (4)

• Measurement of changes in esophageal sensitivity after IV naloxone or IM methylnaltrexone administration

  Investigation of the effect of Naloxone and methylnaltrexone-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 naloxone and methylnaltrexone condition to see if CRH affects the sensitivity to increasing temperature

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

• Measurement of changes in esophageal sensitivity after IV naloxone or IM methylnaltrexone administration

  Investigation of the effect of Naloxone and methylnaltrexone-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 Naloxone and methylnaltrexone condition to see if Naloxone and methylnaltrexone affect the sensitivity to increasing balloon volume.

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

• Measurement of changes in esophageal sensitivity after IV naloxone or IM methylnaltrexone administration

  Investigation of the effect of Naloxone and methylnaltrexone-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 Naloxone and methylnaltrexone condition to see if Naloxone and methylnaltrexone affect the sensitivity to increasing electrical pulses.

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

• Measurement of changes in esophageal sensitivity after IV naloxone or IM methylnaltrexone administration

  Investigation of the effect of Naloxone and methylnaltrexone-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 Naloxone and methylnaltrexone condition to see if Naloxone and methylnaltrexone affect the sensitivity to acid infusion.

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

Study Arms (3)

Naloxone

ACTIVE COMPARATOR

Administration of a centrally acting µ-opioid receptor antagonist Naloxone (20µg/kg/h intravenous infusion after 0.4mg bolus) to investigate the effect of esophageal sensitivity assessed by multimodal esophageal stimulation.

Drug: Naloxone

Methylnaltrexone bromide

ACTIVE COMPARATOR

Administration of a peripherally acting µ-opioid receptor antagonist Methylnaltrexone (12mg/0.6mL subcutaneous injection) to investigate the effect of esophageal sensitivity assessed by multimodal esophageal stimulation.

Drug: Methylnaltrexone Bromide

Placebo

PLACEBO COMPARATOR

Administration of placebo injection (1mL 0.9% saline IV or 0.6 IM) as a control condition to compare to the administration of naloxone or methylnaltrexone bromide in the multimodal esophageal stimulation protocol.

Other: Placebo

Interventions

Naloxone DRUG

20µg/kg/h intravenous infusion after 0.4mg bolus of Naloxone and 0.6mL IM NaCl (0.9%) injection (this step is necessary to keep the subject blinded for the condition since nalaxone and methylnaltrexone have different administration routes)

Also known as: Naloxon, B.Braun

Naloxone

Methylnaltrexone Bromide DRUG

12mg/0.6mL subcutaneous injection and 1mL bolus of NaCl (0.9%) followed by intravenous infusion (this step is necessary to keep the subject blinded for the condition since nalaxone and methylnaltrexone have different administration routes)

Also known as: Relistor

Methylnaltrexone bromide

Placebo OTHER

0.6 mL of NaCl 0.9% will be injected IM and 1mL bolus injection of NaCl(0.9%) will be administered IV followed by IV NaCl 0.9% infusion

Also known as: Saline solution (0.9% NaCl)

Placebo

Eligibility Criteria

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

You may qualify if:

• to 60 years old
• No history of gastrointestinal symptoms or complaints

You may not qualify if:

• A history of allergic reaction to naloxone or methylnaltrexone bromide or multiple allergies to several foods and drugs.
• Pregnancy, lactation.
• Concomitant administration of monomine oxidase inhibitors (MAOI), verapamil or diltiazem or medications affecting esophageal motility.
• Significant co-morbidities (neuromuscular, psychiatric, cardiovascular, pulmonary, endocrine, autoimmune, renal and hepatic).
• Prior history of esophageal, Ear-Nose-Troat or gastric surgery or endoscopic anti-reflux procedure.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

MeSH Terms

Conditions

Gastroesophageal Reflux

Interventions

Naloxone; methylnaltrexone; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Jan Tack, MD, PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2017
• First Posted: January 9, 2017
• Study Start: October 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 9, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share